Travel Funding Research Articles

Serial Minimal Residual Disease Evaluation in Patients with Chronic Lymphocytic Leukemia Under Long-Term Venetoclax Treatment

Serial Minimal Residual Disease Evaluation in Patients with Chronic Lymphocytic Leukemia Under Long-Term Venetoclax Treatment

Ibrutinib Treatment in Waldenström's Macroglobulinemia: Follow-up Efficacy and Safety from the iNNOVATETM Study

Background: Rituximab (RTX) is commonly used to treat Waldenstrom9s macroglobulinemia (WM). Treatment options are limited for patients (pts) who fail rituximab therapy. Single-agent ibrutinib (ibr) is highly active in WM and is approved in the United States and Europe for WM. In the phase 3 iNNOVATE study, ibr plus RTX resulted in significantly longer PFS and higher response rates vs RTX alone, both among TN and previously treated pts with WM (Dimopoulos MA, et al. N Engl J Med. 2018). Previous reports from the open-label, single-agent substudy showed sustained responses and a manageable toxicity profile in RTX-refractory WM, with a median follow-up of 18.1 mo (Dimopoulos MA, et al. Lancet Oncol. 2016). Follow-up data from both the randomized portion (median follow-up of 30.4 mo) and substudy (median follow-up of 38.7 mo) of iNNOVATE are presented. Methods: Pts had confirmed, symptomatic WM requiring treatment. Pts in the randomized portion (Arms A and B) with prior RTX therapy required a response (≥MR) to their last RTX-based regimen. Pts were randomized to daily 420 mg ibr (Arm A; IR) or placebo (Arm B; R) plus RTX (375 mg/m2/week IV at weeks 1-4 and 17-20). In Arm C, pts who failed to achieve ≥MR or relapsed Results: A total of 150 pts were randomized to Arms A and B (n=75/arm; Table 1). Median age was 69 y. High IPSSWM was reported in 38% of pts; 45% of pts were treatment naive. With prolonged follow-up and a median duration of treatment of 29.5 mo with IR and 15.5 mo with R, investigator-assessed major response rates (≥PR) were 77% with IR vs 33% with R (P In Arm C, 31 pts received single-agent ibr (Table 1). Median age was 67 y. Most (71%) pts had ≥3 prior therapies; all patients were RTX-refractory and 90% had prior treatment with cyclophosphamide. High IPSSWM was reported in 42% of pts. With longer follow-up, median investigator-assessed PFS was NR (95% CI: 27.6-NR); estimated 36-mo PFS was 61%. Major response rate by investigator assessment was 77% and ORR was 90%. The estimated 36-mo OS was 84%. Improved Hb level was seen in 71% of pts. Treatment was ongoing in 52% of pts. Median duration of ibr treatment was 37.0 mo, with no major hemorrhagic or atrial fibrillation events reported. Grade ≥3 AEs occurred in 74% of pts and 39% had serious AEs. No fatal AEs were reported. Conclusions: IR showed continued superiority over R, in treatment-naive and previously treated pts with WM, regardless of genotypic factors. Similarly, in heavily pretreated, RTX-refractory pts with follow-up >3 y, single-agent ibr was highly active and response improved over time. Alone or in combination, ibr had a manageable safety profile and no new safety signals were identified with longer follow-up. Disclosures Buske:Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Bayer: Research Funding. Tedeschi:Gilead: Consultancy; AbbVie: Consultancy; Janssen: Consultancy, Speakers Bureau. Trotman:Beigene: Research Funding; Celgene: Research Funding; Janssen: Research Funding; PCYC: Research Funding; Roche: Research Funding; Jassen: Research Funding. Garcia-Sanz:Spanish Government: Research Funding; Pharmacyclics: Research Funding; BMS: Consultancy, Honoraria; Hospira: Research Funding; Gilead: Research Funding; Amgen Inc.: Research Funding; Incyte: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. MacDonald:Roche: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Lundbeck: Honoraria; Seattle Genetics: Honoraria. Leblond:Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Amgen: Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Sandoz: Honoraria; Gilead: Honoraria, Speakers Bureau. Herbaux:Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Tam:Beigene: Honoraria, Other: Travel funding; Roche: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria, Travel funding; Gilead: Honoraria; AbbVie: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Roche: Honoraria; Beigene: Honoraria, Other: Travel funding; Pharmacyclics: Honoraria; Janssen: Honoraria, Research Funding. Palomba:Seres: Honoraria, Patents & Royalties; Juno: Honoraria, Patents & Royalties; Merck: Consultancy; Pharmacyclics: Consultancy; Therakos: Consultancy. Matous:Celgene: Consultancy, Honoraria, Speakers Bureau. Shustik:Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy. Kastritis:Takeda: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Other: Travel, Accommodations, Expenses; Genesis Pharma: Consultancy; Prothena: Consultancy. Treon:Johnson & Johnson: Consultancy; Janssen: Consultancy, Other: Travel, Accommodations, Expenses; BMS: Research Funding; Pharmacyclics: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding. Lih:Abbvie: Employment, Equity Ownership; Abbvie/Pharmacyclics: Other: Travel, Accommodations, Expenses. Li:Pharmacyclics: Employment; Abbvie: Equity Ownership; BMS: Equity Ownership; Pfizer: Equity Ownership; Abbott: Equity Ownership; Amgen: Equity Ownership; Gilead: Equity Ownership; Biogen: Equity Ownership; Celgene: Equity Ownership; Medivation: Equity Ownership; Merck: Equity Ownership; Exelixis: Equity Ownership; Juno: Equity Ownership; Isis: Equity Ownership; Aduro: Equity Ownership; Merrimack: Equity Ownership. Salman:Pharmacyclics LLC: Employment, Equity Ownership; Abbvie: Equity Ownership. Graef:Abbvie: Equity Ownership, Patents & Royalties; Pharmacyclics: Employment, Other: Leadership, Patents & Royalties. Dimopoulos:Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria.

Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group: MPN Experimental Assessment of Symptoms By Utilizing Repetitive Evaluation (MEASURE) Trial

Background:Myeloproliferative neoplasms (MPN) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal hemopathies characterized by burdensome symptom profiles and impaired quality of life. Treatments include pharmacologic approaches, phlebotomy, and bone marrow transplant. Outcome studies have historically focused on hematologic improvement and survival benefit. Few prospective studies have evaluated patient-reported symptoms and quality of life outcomes after standard therapy. The Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group aims to objectively quantify symptomatic response to standard treatments. Here we provide updated results for the prospective MPN Experimental Assessment of Symptoms by Utilizing Repetitive Evaluation (MEASURE) trial.Methods:The MEASURE trial is a prospective international cohort study evaluating responsiveness of the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS or MPN-10) in an anticipated 480 ET, PV, and MF patients receiving non-experimental medical therapy and/or phlebotomy.Patients complete the MPN-SAF TSS (JCO 2012) for seven consecutive days at enrollment then again for seven days between 90 days and six months later. Patients also complete the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and M.D. Anderson Symptom Inventory (MDASI) instruments at enrollment and on the first day of the second assessment. Physicians report demographic, laboratory, and clinical data.Results:DemographicsTo date, 340 patients have enrolled and 270 have completed both study visits. Participants include ET (60%), PV (29%), and MF (12%; including 68% primary MF, 12% post-ET, 20% post-PV) patients. Enrolled patients are 51% male. The most common therapies received prior to enrollment were aspirin (34%), phlebotomy (15%), hydroxyurea (14%), and warfarin/clopidogrel/anticoagulation (6%). The most common current MPN therapies were hydroxyurea (67%), aspirin (24%), phlebotomy (9%), and ruxolitinib (8%). Information on mutational analysis was also collected; 77% of patients have a known JAK2 V617F mutation, 3% have an MPL W515 mutation.Symptom MeasuresOn the MPN-SAF TSS, the majority of individual symptoms assessed did not change significantly between the two assessment time points while on standard therapy. Notable exceptions were a significant decrease in weight loss (mean 2.0 vs. 1.7 on a 0=absent to 10=worst imaginable scale, p=0.005) and a significant worsening in quality of life (mean 3.6 vs. 3.8 on a 0=as good as it can be to 10=as bad as it can be scale, p=0.04). No changes were seen in other symptoms including early satiety, abdominal discomfort, night sweats, fatigue, inactivity, poor concentration, bone pain, itching, or fever. Similarly, the cumulative MPN-SAF TSS score remained stable at a mean of 24.4 over the treatment period. These findings were congruent with those observed using the EORTC QLQ-C30 instrument, with no significant changes seen in emotional, physical, role, cognitive, or social functioning. Finally, the MDASI also revealed a lack of change in either symptom severity (mean 2.7) or symptom distress (mean 3.0) scores, which remained stable over the study period.Discussion:Myeloproliferative neoplasms are associated with burdensome symptoms that significantly compromise quality of life. To date, no studies have quantified symptomatic response to standard-of-care treatments. Overall, results from the MEASURE study suggest that standard treatments have limited systematic impact on patient symptomatology over time, with no improvements in overall quality of life. However, we note the relatively low proportion of patients in this cohort treated with ruxolitinib, which has been shown previously to improve symptom burden, and this may have impacted the symptom responses seen in the group as whole; detailed responses by treatment and MPN subtype will be presented. [Display omitted] DisclosuresDueck:Pfizer: Honoraria; Bayer: Employment; Phytogine: Employment. Ross:BMS: Honoraria; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Research Funding. Tam:Janssen: Honoraria, Research Funding; Gilead: Honoraria; AbbVie: Honoraria, Research Funding; Pharmacyclics: Honoraria, Travel funding; AbbVie: Honoraria, Research Funding; Roche: Honoraria; Beigene: Honoraria, Other: Travel funding; Pharmacyclics: Honoraria; Gilead: Honoraria; Roche: Honoraria; Beigene: Honoraria, Other: Travel funding. Radia:Novartis: Speakers Bureau; Blueprint: Consultancy. Mesa:UT Health San Antonio - Mays Cancer Center: Employment; Celgene: Research Funding; NS Pharma: Research Funding; Pfizer: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Promedior: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Novartis: Consultancy.

Phase 2 Expansion Study of Oral Rigosertib Combined with Azacitidine (AZA) in Patients (Pts) with Higher-Risk (HR) Myelodysplastic Syndromes (MDS): Efficacy and Safety Results in HMA Treatment Naïve & Relapsed (Rel)/Refractory (Ref) Patients

Phase 2 Expansion Study of Oral Rigosertib Combined with Azacitidine (AZA) in Patients (Pts) with Higher-Risk (HR) Myelodysplastic Syndromes (MDS): Efficacy and Safety Results in HMA Treatment Naïve & Relapsed (Rel)/Refractory (Ref) Patients

Association between Transplant Volumes and 30-Day Readmissions Following Allogeneic Hematopoietic Cell Transplantation (allo-HCT) in the US

Background: Readmissions within 30 days after index hospitalization is a quality and cost-containment metric. Financial penalties to hospitals with high rates of risk-adjusted readmissions have been expanded beyond medical conditions like heart failure and pneumonia. Published data show significant heterogeneity in readmission rates and recent data from elderly Medicare beneficiaries reported a 17.8% readmission rate for targeted conditions. Allo-HCT is a widely used therapeutic strategy in the management of various hematologic disorders like acute myelogenous (AML) and lymphoblastic leukemia (ALL). However, allo-HCT readmission rates are poorly described, and limited to single center studies only. The association between institution HCT volume and 30-day readmission metric has not been examined.Methods: In this observational study, we used the 2012-2014 Nationwide Readmission Database (NRD) to identify hospitals with established allo-HCT programs. Patients ≥18 years of age, discharged from hospital following an allo-HCT (identified using ICD-9 procedure code of 41.02, 41.03, 41.05, 41.06, or 41.08) were included. Annual hospital case volume was calculated as the sum of all discharges with allo-HCT within the calendar year; low, medium, and high annual case volume groups were created based on (survey weighted) tertiles of patients (pts.) in the analytic data domain (Figure 1). Rates, causes, and costs of 30-day readmissions were compared between low-, medium-, and high-volume hospitals. The analysis was limited to urban teaching hospitals and pts. admitted during month of December were excluded. The primary outcome, was the unplanned 30-day re-admission following allo-HCT. Multiple logistic regression was used to model each 30-day readmission outcome including hospital case volume with other predictors (age, sex, disease type, stem cell source, co-morbidity index, primary insurance, length of stay, infection and acute graft-versus-host-disease (aGVHD) at index admission, discharge disposition and median income quartile).Results: A total of 17,214 (weighted) allo-HCTs were performed during the time period. Baseline characteristics of pts. in low (<58 allo-HCTs/yr.)-, medium (58-158 allo-HCTs/yr.)- and high-volume (>158 allo-HCTs/yr.) hospitals were comparable as shown in Table 1. The overall rates of readmissions were significantly higher in low volume centers (24.7.4%; SE, 1.5) compared to medium (21.4% (1.7) and high volume (9.5% (1.8), centers (p=0.03). The mean time to readmission in low vs. medium vs. high volume centers was, 11.6 [0.39] days vs. 12 [0.26] days vs. 11.5 [0.57] days respectively, (p <0.001). The length of readmission stay was significantly longer in low volume centers (mean [SD], 12.8 [0.64] days vs. 12.3 [0.91] days vs. 10.6 [0.80] days; p=<0.001) respectively. Consequently, cost per readmission was significantly higher in low volume centers (mean [SD], $164,349 [12,328] vs. $140,327 [15,297] vs. $107,362 [11,665]; p<0.001).Readmission rates in low volume and medium volume centers compared to high volume centers were: adjusted odds ratio (aOR) 1.39, 95% CI 1.08-1.77; p =0.01 and 1.18, 95% CI, 0.89-1.55; p=0.23, respectively. Other significant predictors of readmission included disease type (ALL vs. AML): aOR 1.32, 95% CI 1.07-1.63; p= 0.009), type of primary insurance (Medicare vs. private): aOR 1.17, 95% CI 1.01-1.35; p=0.02; Elixhauser co-morbidity index (≥1 vs. 0): aOR 1.4, 95% CI 1.2-1.7; p= 0.001 and stem cell source (cord blood vs. peripheral blood; aOR 2.4, 95%CI 1.85-3.2, p<0.001). Patients with any infection and the presence of aGVHD at index admission did not have an effect on readmission rates. Neutropenia, fever, viral infection, sepsis, acute renal failure, and pneumonia were the most common reasons for readmission.Conclusions: The likelihood of readmission after allo-HCT is elevated in centers performing <58 allo-HCTs/year, in those pts. with ≥1 co-morbidities, cord blood transplants, in ALL pts. and in Medicare beneficiaries. Lower readmission at higher-volume centers was associated with significantly lower cost to the health care system. There are important limitations with the use of data from NRD particularly the lack of information on donor status and conditioning regimen. Despite these shortcomings, the information may aid health care when developing quality-of-care metric for allo-HCT. DisclosuresDhakal:Amgen: Honoraria; Takeda: Honoraria; Celgene: Consultancy, Honoraria. Shah:Geron: Equity Ownership; Lentigen Technology: Research Funding; Juno Pharmaceuticals: Honoraria; Oncosec: Equity Ownership; Miltenyi: Other: Travel funding, Research Funding; Exelexis: Equity Ownership. D'Souza:Prothena: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Research Funding; Merck: Research Funding; Amgen: Research Funding. Hari:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding; Kite Pharma: Consultancy, Honoraria; Sanofi: Honoraria, Research Funding; Amgen Inc.: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Spectrum: Consultancy, Research Funding. Hamadani:Sanofi Genzyme: Research Funding, Speakers Bureau; MedImmune: Consultancy, Research Funding; Celgene Corporation: Consultancy; Takeda: Research Funding; Cellerant: Consultancy; ADC Therapeutics: Research Funding; Ostuka: Research Funding; Janssen: Consultancy; Merck: Research Funding.

Point-of-Care Manufacturing of CD20.19 Bi-Specific Chimeric Antigen Receptor T (CAR-T) Cells in a Standard Academic Cell Processing Facility for a Phase I Clinical Trial in Relapsed, Refractory NHL

Adoptive cell therapy with autologous CAR-T cells has induced remarkable responses in patients with treatment-refractory hematologic malignancies, which has led to FDA approvals for two CAR-T products. However, limitations exist with commercial CAR-T centralized production: (1) off-site manufacturing can take several weeks and requires shipping from and to the treating facility; (2) off-site manufacturing limits treatment options for progressing patients; (3) high cost of the commercial products may limit their availability. To address these challenges, we used the fully automated Miltenyi CliniMACS Prodigy device, a GMP-compliant closed system, to manufacture autologous CAR-T cells for a Phase I trial (NCT03019055) evaluating a first-in-human bi-specific CAR that targets CD19 and CD20 (CD20.19 CAR).CAR-T manufacturing was performed exclusively using the CliniMACS Prodigy device and reagents obtained from Miltenyi Biotec. Production was performed within the Medical College of Wisconsin (MCW) Cell Therapy Laboratory, an ISO7 air handling environment. Manufacturing was set at 14 days, and production was as follows. First, peripheral blood mononuclear cells (MNC) were collected by apheresis, with a collection goal of 4 blood volumes to eliminate risk of a low CD3 yield in heavily pre-treated patients. Next, MNC were loaded onto the Prodigy, and CD4 and CD8 T cells enriched by positive immunomagnetic selection. To start the culture process, enriched T cells were suspended in TexMACS medium supplemented with 3% human AB serum and 200 U/mL IL-2, and TransACT reagent was added to stimulate the T cells in the Prodigy cell culture chamber. The following day (day 1), lentiviral vector expressing anti-CD19 and anti-CD20 (in tandem) with CD3ζ and 4-1BB stimulatory domains was added to the stimulated cells. Culture washes and feedings were done on days 5, 6, 8, 10 and 12 of manufacture, and final products harvested on Day 14. Protein L staining was used to detect expression of CD20.19 CAR on the T cells. On Day 14, eligible patients received fresh CAR-T cells, while for others the product was cryopreserved and administered on a later date.To date, the MCW Cell Therapy Laboratory has successfully generated CAR-T cell products for all 6 patients enrolled thus far on the Phase 1 clinical trial with no production failures (Table 1). Three patients received cryopreserved product and 3 patients received fresh product. The enriched T cells were 94.3% CD3+ (87.8-97.4%), and average T cell recovery from the apheresis cell products was 65.2% (54.2-80.0%). Protein L staining indicated 20.8% average CD20.19 CAR expression. Patient CAR-T cells were able to kill CD19+ and CD20+ target cells in vitro and produce IFN-gamma in response to the same target cells. An average yield of 5.9e+8 (4.3-7.9e+8) CAR T cells was obtained at harvest, which exceeded the required cell dose for all patients. The CAR-T cells were comprised of both CD4 and CD8 T cells, with higher expression on CD4 T cells; average CAR-T CD4:CD8 ratio on the final products was 2.8. The majority of T cells (average of 81.5%) had an effector-memory phenotype. In-process testing performed on Day 8 of manufacturing demonstrated sufficient numbers of CAR-T cells needed for patient infusions were already present, and that the CAR-T cells only expanded an additional 1.9 to 3.5-fold between Days 8 and 14.In conclusion, we have successfully demonstrated feasibility for point-of-care CAR-T cell production for clinical use from patient apheresis products utilizing the CliniMACS Prodigy device. Time to production was efficient (14 days), and patient-derived CAR-T cell products were reproducibly generated in a standard cell processing laboratory within an academic medical center. A major clinical advantage of CAR-T cells generated on-site is the flexibility in treatment. Patients can receive cells either immediately (i.e., fresh) or the cells can be cryopreserved for later infusion if the patient is not able to receive fresh cells. Based on our results, we intend to decrease the cell processing time to 10 days. [Display omitted] DisclosuresZhu:Lentigen Technology Inc., A Miltenyi Biotec Company: Research Funding. Shah:Juno Pharmaceuticals: Honoraria; Oncosec: Equity Ownership; Geron: Equity Ownership; Exelexis: Equity Ownership; Miltenyi: Other: Travel funding, Research Funding; Lentigen Technology: Research Funding. Schneider:Lentigen Technology Inc., A Miltenyi Biotec Company: Employment. Keever-Taylor:Medical College of Wisconsin: Research Funding. Dropulic:Lentigen, A Miltenyi Biotec company: Employment. Orentas:Lentigen Technology Inc., A Miltenyi Biotec Company: Employment. Hari:Bristol-Myers Squibb: Consultancy, Research Funding; Amgen Inc.: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Kite Pharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding. Johnson:Miltenyi: Research Funding.

PD-L1 Blockade with Atezolizumab in Higher-Risk Myelodysplastic Syndrome: An Initial Safety and Efficacy Analysis

PD-L1 Blockade with Atezolizumab in Higher-Risk Myelodysplastic Syndrome: An Initial Safety and Efficacy Analysis

Trends in Post-Relapse Survival in Classical Hodgkin Lymphoma Patients after Experiencing Therapy Failure Following Autologous Hematopoietic Cell Transplantation

BackgroundClassical Hodgkin Lymphoma (cHL) is a highly curable disease; however, 10% of patients (pts) with limited stage and 20%-30% with advanced stage disease still fail first line-treatment. Autologous hemopoietic cell transplantation (auto-HCT) is the standard of care in pts who fail to achieve remission with first-line therapy, or who relapse after induction chemotherapy. However, approximately 50% of cHL pts will ultimately relapse post auto-HCT. These pts historically have had poor outcomes, with median survival in the 1.5 year range. In recent years, highly active new therapies such as brentuximab vedotin (BV), checkpoints inhibitors (i.e. nivolumab and pembrolizumab), and increased accessibility to allogeneic HCT (including utilization of haploidentical donors) have become more widely available. We hypothesized that, in recent years, survival has improved in cHL patients who relapse after auto-HCT since the introduction of these novel therapies into more widespread clinical practice.MethodsWe conducted a multi-center retrospective study from 3 academic institutions in the U.S. (Medical College of Wisconsin, Ohio State University, and Washington University in St. Louis) to evaluate survival of cHL pts after the failure of an auto-HCT. We reviewed 341 pts who received auto-HCT from 2006-2015. Among them, 126 (37%) pts relapsed post auto-HCT and were evaluated in more detail. For the purpose of analysis, pts were divided into 2 cohorts based on timing of auto-HCT; 2006-2010 (Cohort 1, n=57) and 2011-2015 (Cohort 2, n=69) to compare outcomes.ResultsThe median age at auto-HCT, time from diagnosis to transplant, time from transplant to relapse were similar in Cohort 1 & 2 (see Table 1). The proportion of pts who achieved complete remission (CR) at the time of auto-HCT were 22.8% in Cohort 1 and 40.6% in Cohort 2. Whereas, 68.4% of pts in Cohort 1 and 52.2% of pts in Cohort 2 had partial remission (PR) at the time of auto-HCT. The median number of lines of therapy after relapse from auto-HCT were 2 each in Cohort 1 (range, 0-13) and Cohort 2 (range, 0-7), respectively (p= 0.74). Twenty-five (45%) pts in Cohort 1 and 49 (73%) pts in Cohort 2 received BV as a salvage therapy post auto-HCT (p= 0.002). Similarly, 3 (5.5%) pts in Cohort 1 versus (vs.) 21 (32%) pts in Cohort 2 received check point inhibitors as salvage therapy post auto-HCT relapse (p= <0.001). Fourteen (25%) pts in Cohort 1 and 26 (38%) pts in Cohort 2, received allogeneic HCT after relapse from auto-HCT (p= 0.10). At 5 years follow up after relapse from auto-HCT, 36.5% of pts were alive in Cohort 1 and 58.3% of pts in Cohort 2 (p= 0.03) (Fig. 1A). The proportion of pts alive at 5 years follow up from time of auto-HCT (using left truncation analysis) was 34% and not reached (NR) in Cohort 1 and Cohort 2, respectively (p= 0.02) (Fig.1B). We performed multivariate analysis for overall survival (OS) from time of auto-HCT relapse; Cohort 1 vs. 2 (HR; 0.35, 95% CI 0.18-0.65, p= 0.0009), disease status at auto-HCT (CR vs. progressive disease [PD]) (HR; 2.51, 95% CI 0.85-7.34, p= 0.01), age at auto-HCT (HR; 1.04, 95% CI 1.01-1.06, p= 0.0005) and time to relapse from auto-HCT (HR; 0.61, 95% CI 0.48-0.76, p= <0.0001), retained independent prognostic significance for OS.ConclusionOur analysis supports that survival of cHL pts post auto-HCT failure has significantly improved in recent years (2011-2015), most likely due to incorporation of novel therapies including BV, checkpoint inhibitors, and more widespread use of allogeneic HCT. [Display omitted] DisclosuresShah:Miltenyi: Other: Travel funding, Research Funding; Juno Pharmaceuticals: Honoraria; Exelexis: Equity Ownership; Oncosec: Equity Ownership; Geron: Equity Ownership; Lentigen Technology: Research Funding. Hamadani:Celgene Corporation: Consultancy; Janssen: Consultancy; MedImmune: Consultancy, Research Funding; ADC Therapeutics: Research Funding; Takeda: Research Funding; Cellerant: Consultancy; Ostuka: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding.

Incidence and Predictors of 30-Day Readmissions Following Autologous Hematopoietic Cell Transplantation (auto-HCT) in the US

Background: Readmissions within 30 days after index hospitalization is a quality, and cost-containment metric. It is now a major issue for hospitals, physicians and policy makers. Financial penalties to hospitals with high rates of risk adjusted readmissions have been expanded beyond medical conditions like heart failure and pneumonia. Auto-HCT is a widely used therapeutic strategy in the management of various hematological disorders, particularly multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) in the US. However, auto-HCT readmission rates are poorly described in the literature and often limited to single center studies. To better address the incidence and underlying predictors of 30-day readmission following auto-HCT, we performed an analysis of the Nationwide Readmission Database(NRD).Methods: NRD data was queried from 2012-2014 to identify patients >18 years of age discharged from the hospital after auto-HCT (identified as presence of any ICD-9 procedure codes 41.00, 41.01, 41.04, 41.07, or 41.09). Survey weighted domain analysis was conducted to study incidence of 30-day readmission by center volume. Annual hospital case volume was calculated as the sum of all discharges with auto-HCT within the calendar year; low, medium, and high annual case volume groups were created based on (survey weighted) tertiles of patients (pts.) in the analytic data domain (Figure 1). Rates, causes, and costs of 30-day readmissions were compared between low-, medium-, and high-volume hospitals. The analysis was limited to urban teaching hospitals, and pts. admitted during month of December were excluded. The primary outcome was the unplanned 30-day re-admission following auto-HCT. Multiple logistic regression was used to model each 30-day readmission outcome including hospital case volume with other predictors (age, sex, disease type, primary insurance, median income, discharge disposition, co-morbidity, length of stay (LOS) and infection at index hospitalization).Results: A total of 28,356 (weighted) auto-HCTs were performed during the time period and MM remains the most common indication (~60%). Baseline characteristics of pts. in low (<78/yr.)-, medium (78-187/yr.)- and high-volume (>187/yr.) hospitals were comparable as shown in Table 1. The overall rates of readmissions were significantly higher in low volume 15.7% (SE, 1.5) compared to medium 9.9% (1.5) and high volume 9.5% (1.8), p=0.002 centers. The mean time to readmission in low vs. medium vs. high volume centers was (8.3 [0.41] days vs. 10.7 [0.78] days vs. 8.9 [0.26] days; p <0.001); however, readmission LOS was significantly longer in low and medium volume centers (mean [SD], 7.2 [0.30] days vs. 8.3 [0.62] days vs. 6.2 [0.25] days; p=<0.001) respectively. Consequently, cost per readmission was significantly higher in low volume centers (mean [SD], $ 65,815 [3492] vs. $ 65,662 [5896] vs. $ 48,914 [4162]; p<0.001).Readmission rates in low volume and medium volume centers compared to high volume centers were: adjusted odds ratio (aOR) 1.68, 95% CI 1.07-2.6; p =0.02 and 1.06 95% CI, 0.61-1.83; p=0.82, respectively. Other significant predictors of readmission included younger age (≥50 vs. <49) (aOR 0.81, 95% CI 0.68-0.98; p=0.03), female sex (aOR 1.20, 95% CI 1.06-1.36; p=0.003), disease type (others vs. MM) (aOR 1.37 95% CI 1.07-1.55; p= 0.018); and Elixhauser co-morbidity index (≥20 vs. 0; aOR 1.5, 95% CI 1.16-1.92; p= 0.00). Patients with non-routine discharges (discharges other than home) (aOR 1.3, 95% CI 1.1-1.7, p= 0.005), and shorter index LOS (aOR 0.94, 95% CI 0.89-0.98; p=0.01) were associated with higher readmission rates. The most common causes of readmission included: fever, neutropenia, infections, pneumonia, hyovolemia, nausea, vomiting and acute kidney injury.Conclusions: This is the largest study till date reporting on the incidence and predictors of 30-day readmissions following auto-HCT in the US. The overall 30-day readmission rates following auto-HCT was ~12%. We report an inverse association with hospital auto-HCT volume (<78/yr.) and 30-day readmissions. Shorter LOS at index admission was associated with higher rates of readmission, which was associated with significantly higher cost to the health care system. These data should provide guidance when developing quality indicators and any policies penalizing hospitals for auto-HCT readmission. [Display omitted] DisclosuresDhakal:Celgene: Consultancy, Honoraria; Takeda: Honoraria; Amgen: Honoraria. Shah:Lentigen Technology: Research Funding; Oncosec: Equity Ownership; Exelexis: Equity Ownership; Miltenyi: Other: Travel funding, Research Funding; Juno Pharmaceuticals: Honoraria; Geron: Equity Ownership. D'Souza:Takeda: Research Funding; Merck: Research Funding; Celgene: Research Funding; Prothena: Consultancy, Research Funding; Amgen: Research Funding. Hari:Spectrum: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria; Amgen Inc.: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Hamadani:Celgene Corporation: Consultancy; Ostuka: Research Funding; Cellerant: Consultancy; ADC Therapeutics: Research Funding; Janssen: Consultancy; MedImmune: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Takeda: Research Funding; Merck: Research Funding.

Response to Venetoclax and Hypomethylating Agents Among Prognostic Risk Groups and Genetic Subtypes of Acute Myeloid Leukemia

▪The combination of venetoclax and hypomethylating agents (HMA) has demonstrated potent activity in acute myeloid leukemia (AML), both in newly diagnosed patients (pts) and those with relapsed/refractory (r/r) disease. We analyzed the association between response to therapy and leukemic somatic mutations, cytogenetics, and other pertinent patient- and leukemia-related features in a large series of newly diagnosed and r/r AML in adults treated with venetoclax in combination with HMA at City of Hope between October 2016 and May 2018.We identified 107 evaluable adults with AML treated with the combination of venetoclax and HMA. Sixty-one (57%) pts had r/r AML at the time of initiating treatment (median prior lines of therapy: 2; range: 1-10), while 46 (43%) were treated in the frontline setting. The median age of pts was 68 years (range: 19-86). AML was de novo in 57 (53%), therapy-related in 23 (21%) and secondary in 27 (25%) pts. Thirty-six (34%) pts had prior exposure to HMA, and 21 (20%) pts had relapsed following prior allogeneic hematopoietic cell transplantation (HCT). The majority of treated pts had unfavorable (52%) or intermediate-risk (39%) AML based on combined cytogenetics and molecular profiles. The most common detected somatic mutations (majority by next generation sequencing) were FLT3 (17%), followed by DNMT3A (15%), RAS and TET2 (each 14%), RUNX1 (13%), TP53 (12%), and IDH1/2 (11%). Most pts received decitabine in combination with venetoclax (N=97, 91%); only 10 (9%) pts received 5-azacitidine together with venetoclax.Complete remission (CR)/CR with incomplete hematologic recovery (CRi) was achieved in 57 (53%) pts after a median of 2 (range 1-4) cycles. For 36 pts who achieved CR/CRi and had available minimal residual disease (MRD) assessment by multicolor flow cytometry (MFC), 23 (64%) became MRD-. CR/CRi was higher in pts carrying favorable- or intermediate-risk AML compared to poor-risk AML (100% vs. 60% vs. 45%, P=0.029). CR/CRi was 48% in those with complex cytogenetics (N = 31), 45% in monosomal karyotype (N = 22), 36% in KMT2A gene rearrangement (N = 11), 74% in normal karyotype (N = 19), and 25% in inversion 3 (N =4). The CR/CRi rate was not significantly different between newly diagnosed or r/r AML (61% vs. 48%, P = 0.17), nor was there a difference associated with AML type (de novo vs. therapy-related vs. secondary, P= 0.26), patient age (> or ≤ 65 years) at time of therapy (P = 0.13), prior allogeneic HCT (P = 0.29), prior administration of HMA (P = 0.37) and the type or schedule (5- or 10-day decitabine) of HMA (P = 0.52). In multivariate analysis, only favorable- or intermediate-risk cytogenetics was associated with better CR/CRi (P = 0.036). CR/CRi was also comparable regardless of the presence or absence of various analyzed somatic AML mutations. However, in recursive partitioning analysis of detectable somatic mutations and response to therapy, the combined lack of RAS, TP53 and RUNX1 mutations was linked to an improved rate of CR/CRi. When AML cases were stratified into functional gene alteration subgroups (according to the TCGA data set), there was no significant difference in CR/CRi according to the presence or absence of certain functional genes/fusions.Median overall survival (OS) for all pts was 12.5 months and was 14.6 months for pts who achieved CR/CRi, in contrast to 4.6 months for non-responders (P <0.001). Only AML subtype (de novo vs. therapy-related vs. secondary) (P <0.001) and AML genetic risk (favorable/intermediate vs. high) (P = 0.042) independently impacted OS in multivariate analysis. None of the AML individual somatic mutations influenced OS for this cohort, however, in recursive partitioning analysis of detectable mutations, the presence of any of SRSF2, IDH1/2 or RUNX1 were associated with improved OS. Furthermore, the presence of myeloid transcription factor (P = 0.033) and spliceosome complex mutations (P = 0.004) predicted superior OS, whereas the presence of a chromatin modifying mutation predicted inferior OS (P = 0.004). Thirteen (23%) responders subsequently underwent allogeneic HCT.We report remarkable activity with venetoclax and HMA across various high-risk genetics and clinical features in AML patients. Prospective studies are warranted to compare this combination directly with chemotherapy in all AML subsets. This is particularly true for high risk AML where response to conventional chemotherapy is poor. [Display omitted] DisclosuresAli:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Salhotra:Kadmon Corporation, LLC: Consultancy. Khaled:Alexion: Consultancy, Speakers Bureau; Juno: Other: Travel Funding; Daiichi: Consultancy. Stein:Celgene: Speakers Bureau; Amgen Inc.: Speakers Bureau. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

PRMT1 Mediated FLT3 Methylation As a Therapeutic Vulnerability in FLT3-ITD+ AML

The current view is that treatment failures of AML patients are due to persistence of leukemia stem cells (LSCs). The presence of FMS-like tyrosine kinase-3 (FLT3) Internal tandem duplication (ITD) is associated with poor prognosis. But, FLT3 tyrosine kinase inhibitors (TKI) demonstrate transient clinical activity in FLT3-ITD+ AML patients. Persistent FLT3-ITD+ AML LSC represent a source of relapse. There is a pressing need to target LSC and improve outcomes for FLT3-ITD+ AML patients.PRMT1, the predominant arginine methyltransferase, has been implicated in pathogenesis of AML rare subtype (i.e., acute megakaryoblastic leukemia). Herein, we show that PRMT1 protein expression is significantly increased in LSC-enriched AML CD34+CD38- cells relative to the counterparts of normal peripheral blood stem cells (PBSC) (AML n=9, normal n=8, p=0.0004,). Following PRMT1-knockdown (KD), AML CD34+ cells (n=15) demonstrated varying degrees of apoptosis while the survival of normal cells were not affected. Interestingly, we observed significant apoptosis-induction in a subset of samples bearing FLT3-ITD mutation (6 out of total 15) upon PRMT1-KD (ShCtrl 13.9±3.6%, ShPRMT1 32.5±4.6%, p<0.001). PRMT1-KD induced apoptosis was also more evident in cord blood (CB) CD34+ cells expressing FLT3-ITD (ShCtrl 19.4±1.3%, ShPRMT1 45.2±2.5%, p<0.001) relative to that of FLT3-WT (ShCtrl 27.47±1.8%, ShPRMT1 36.9±1.6%, p=0.0167). In 293T cells ectopically overexpressing FLT3-WT or FLT3-ITD, co-immunoprecipitation (co-IP) indicated greater interaction between PRMT1 and FLT3-ITD. Through RNA-Seq profiling two AML lines (MV4-11, OCI-AML3) plus one FLT3-ITD transduced CB CD34+ cells with PRMT1-KD, we obtained a differentially-regulated gene set as a “PRMT1 signature”. This signature was enriched in FLT3-ITD+ AML relative to FLT3-WT AML according to ssGSEA analysis using two AML datasets (GSE14468, GSE10358), indicating PRMT1 may cooperate with FLT3-ITD regulating AML maintenance.Given that PRMT1 directly interacts with FLT3-ITD, we next asked whether PRMT1 catalyzes FLT3-ITD protein methylation. Through mass-spectrometry analysis of a FLT3-ITD+ AML specimen and in vitro methylation assay, we identified that PRMT1 catalyzes FLT3-ITD arginine (R) methylation (Me) at two conserved residues, 972 and 973. Using in-house R972/973 Me antibody, we validated the expression of FLT3 R-Me in FLT3-ITD AML speciemens (7 out of 7). To test R-Me function, we transduced MLL-AF9 (MA9) overexpressing murine c-Kit+ cells with methylation-deficient FLT3-ITD (R972/973K, arginine [R] to lysine [K]) construct, and found that MA9 cells expressing R972/973K underwent more apoptosis than that of WT FLT3-ITD (WT FLT3-ITD 9.7±1.1%, R972/973K 23.7±2.1%, p=0.003). The double transformed cells were further transplanted into recipients for leukemia development. Mice receiving MA9 cells expressing R972/973K exhibited longer survival (median survival: WT FLT3-ITD 36 days, R972/973K 50 days, p=0.002, n=6). Mechanistically, expression of R972/973K did not affect the total tyrosine phosphorylation level of FLT3-ITD. Additionally, FLT3-ITD R-Me expression persisted after a TKI (AC220) treatment. These facts indicated that FLT3-ITD R-Me function is independent of FLT3-ITD kinase activity. We then used a FLT3-ITD+ patient derived xenograft (PDX) model to assess the effects of TKI and PRMT1 inhibition. Following engraftment >1% in peripheral blood, we divided mice (n=24) into 4 groups and treated each with vehicle, MS023 (a type I PRMT inhibitor, ACS Chem Biol. 2016;11:772-781) (160 mg/kg/i.p), AC220 (10 mg/kg/i.g) or combination for 4 weeks. MS023 treatment downregulating FLT3 R-Me levels enhanced elimination of FLT3-ITD AML cells by AC220 treatment (AC220 24.6±13.4% vs combination 7.6±6.5%, p=0.02, n=6). At 16 weeks post-secondary BMT, significant AML burden in single drug treated transplants was observed, but less AML cells were detected in combination-treated transplants (AC220 52.3%, vs combination 25.4%, p<0.001, n=6). MS023 had little effect on long-term in vivo engraftment of CD34+ from a human CB specimen (vehicle 76.3±5.9%, MS023 72.2±3.4%, p=0.21, n=5).In summary, our study demonstrated PRMT1 overexpression contributes to AML stem/progenitor cell survival possibly through FLT3-ITD methylation, supporting further exploration into how PRMT1-mediated FLT3 methylation governs LSC survival. DisclosuresKhaled:Alexion: Consultancy, Speakers Bureau; Daiichi: Consultancy; Juno: Other: Travel Funding.

CD20-Tcb (RG6026), a Novel “2:1” Format T-Cell-Engaging Bispecific Antibody, Induces Complete Remissions in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma: Preliminary Results from a Phase I First in Human Trial

CD20-Tcb (RG6026), a Novel “2:1” Format T-Cell-Engaging Bispecific Antibody, Induces Complete Remissions in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma: Preliminary Results from a Phase I First in Human Trial

Improvements in Clinical Outcomes of Advanced Stage Classical Hodgkin Lymphoma in the United States from 2000-2014: Analysis of Surveillance Epidemiology and End Results Database

Background:Advanced Stage Hodgkin lymphoma (HL) is a curable malignancy with combination chemotherapy. While most patients are cured with frontline therapy, for those with refractory disease or early progression, historically, the outcomes have been poor. Novel therapies, PET/CT adapted treatment approaches, and improvement in transplantation have changed the management of both frontline and relapsed HL. However, it remains unknown if these developments have improved the clinical outcomes at population level over time.Methods:Using Surveillance Epidemiology and End Results database, we identified patients aged ≥ 18 years with advanced stage (Stage III or IV) pathologically confirmed classical HL as the first primary malignancy,diagnosed between the years 2000-2014, treated with chemotherapy and actively followed. Patients were stratified by date of diagnosis into 3 groups - 2000-2004, 2005-2009, 2010-2014 to assess the trends in overall survival (OS) over time. Race/ethnicity was stratified into non-hispanic whites and minorities (Non-hispanic blacks, Hispanics, other non-hispanic races). Kaplan-Meier method and log rank test were used to analyze the OS among subgroups. Cox proportional hazard regression method was used to determine the influence of period and demographic factors on OS.Cumulative incidence of death from cardiac cause was estimated using the Nelson-Aalen estimates. Statistical analyses were carried out with significant two sided p< 0.05.Results:A total of 9042 patients with a median age of 41 years were included. There were more males (60.1%) and non-Hispanic whites (64.2%) and most patients had nodal disease (98%) (Table 1).The use of frontline radiation therapy decreased in each 5-year time period (21.3% 2000-2004 vs 15.5% 2005-2009 vs 10.7% 2010-2014, p<0.001). In terms of survival, when stratified by the period of diagnosis, the 3-year OS was significantly higher for patients diagnosed between the year 2010-2014 (81.8%) and 2005-2009 (80.6%) than those diagnosed from 2000-2004 (78.5%, p=0.0008 and 0.02 respectively) (Figure 1). Additionally, age was a significant predictor for OS with a decreasing 3-year OS with increasing age (age < 40 - 91.1%, age 41-60 -81.5%, age >60 -54%, p< 0.001, Figure 2).While outcomes were poorest in the age>60 cohort, similar improvements were seen in OS over the three time periods among this patient population (48.6%- 2000-2004 vs 54.3% 2005-2009 vs 56.8% 2010-2014, p=0.005). On multivariate analysis, diagnosis in the earlier period was associated with higher mortality (2000-2004-HR 1.36, 95% CI 1.21-1.53, p< 0.001; 2005-2009 -HR 1.14, 95% CI 1.01-1.28, p=0.02, both compared to reference group 2010-2014). Similarly, minority races (HR 1.36, 95%CI 1.23-1.49, p<0.001) had a higher mortality risk as compared to non-Hispanic whites. Females (HR 0.82, 95%CI 0.75-0.90 p<0.001) and married status (HR 0.80, 95%CI 0.72-0.87, p< 0.001) were associated with significantly lower mortality. While radiation use decreased over time, the cumulative incidence of cardiac related cause of death did not vary significantly among the three-time periods (1.2% vs 1.1% vs 1.1% respectively at 48 months, p=0.85).Conclusions:Survival of patients with advanced stage HL has continued to improve over time suggesting the clinical impact of evolving treatment approaches. Interestingly this improvement has occurred despite the decreasing utilization of radiation therapy over time. This is suggestive of better end of treatment assessment with PET/CT eliminating the need for end of treatment radiation, improved second line therapies that extend survival, or potentially reduction in treatment related toxicities.Despite these encouraging results, the 3-year OS in the contemporary period remains inadequate at 81.8%. Furthermore, significant differences in survival continue to exist among non-modifiable factors such as gender, age, race, and marital status, highlighting the need for continued research to address these discrepancies. Results of this study provide a new baseline to test novel frontline combination regimens. [Display omitted] DisclosuresHamadani:Takeda: Research Funding; Celgene Corporation: Consultancy; Cellerant: Consultancy; Ostuka: Research Funding; Janssen: Consultancy; MedImmune: Consultancy, Research Funding; Merck: Research Funding; ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau. Shah:Miltenyi: Other: Travel funding, Research Funding; Exelexis: Equity Ownership; Oncosec: Equity Ownership; Geron: Equity Ownership; Juno Pharmaceuticals: Honoraria; Lentigen Technology: Research Funding.

T-Replete Haploidentical Cell Transplantation Using Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome: Effect of Transplant Conditioning Regimen Intensity on Outcomes

▪The significance of conditioning regimen intensity on the outcomes of T-cell replete HLA-haploidentical transplants is not known. This study compared outcomes of commonly used myeloablative (MAC) to reduced intensity (RIC) conditioning regimens in 1325 such transplants (AML; n=818; ALL; n=286 and MDS; n=221) in the US between 2008 and 2016. The median age of the study population was 54 years (18 - 70). Most patients (80%) with AML and ALL were in first or subsequent remission; 83% of those with MDS had refractory anemia with excess blasts at transplantation. Fifty-one percent of patients with AML and ALL had intermediate disease risk index (DRI). In contrast, 50% of patients with MDS had high or very high DRI. Patients received MAC (n=526; 40%) or RIC (n=799; 60%) transplant conditioning regimens and a uniform graft-versus-host disease (GVHD) prophylaxis: post-transplant cyclophosphamide, calcineurin inhibitor and mycophenolate. Approximately 50% of patients reported a HCT-CI score of 0-2 in MAC and RIC groups. Sixty-six percent of MAC and 42% of RIC recipients received peripheral blood grafts. Total body irradiation (TBI) + fludarabine (TBI/Flu; 33%) and busulfan with cyclophosphamide with/without Flu (Bu/Cy ± Flu; 36%) were the predominant MAC regimens. Other MAC regimens included TBI/Cy or other agents (10%), Flu/Bu4 (13%), melphalan (140 mg/m2) + Flu ± thiotepa (Flu/Mel ± TT; 9%). TBI (200cGy)/Cy/Flu (84%) was the predominant RIC regimen. Other RIC regimens included TBI 200cGy + Bu or Mel + Flu (7%), Flu/Bu2 (1%) and Flu/Mel (100mg/m2) ± TT (5mg/kg) (8%). The primary endpoint was disease-free survival (relapse or death). Cox regression models were built to study the effect of conditioning regimens on transplant outcomes after adjusting for other factors significantly associated with outcomes. Differences in transplant-outcomes were observed between ages 18-54 years and 55-70 years. The effect of age was further tested within the 18-54 and 55-70 age groups and there were no differences in outcome. In patients aged 18-54 years (n=689), 55% received MAC and 54% received RIC regimens. In patients aged 55-70 years (n=636), 22% received MAC and 78% received RIC regimens. Table 1 shows the effect (hazard ratio; HR) of conditioning regimen intensity in the two age groups adjusted for HCT-CI, recipient CMV serostatus, disease, DRI and graft type and the 2-year probabilities for the outcomes of interest. In patients aged 18-54 years who were equally likely to receive MAC or RIC regimens, relapse risks were higher after RIC regimens that resulted in lower disease-free survival. There were no differences in non-relapse mortality (NRM) or overall survival by conditioning regimen intensity. In patients aged 55-70 years who were more likely to receive RIC regimen, NRM was lower after RIC but without an advantage for relapse, disease-free or overall survival. Figure 1A and 1B show the 2-year probability of disease-free survival by conditioning regimen intensity in patients aged 18-54 and 55-70 years, respectively. Consistent with the main analysis, a subset analysis limited to AML also confirmed higher relapse (HR 1.43, p=0.03) and lower disease-free survival (HR 1.38, p=0.02) after RIC regimens in patients aged 18-54 years but not in patients aged 55-70 years. Acute GVHD (HR 1.01, p=0.94) and chronic GVHD (HR 0.82, p=0.14) did not differ by conditioning regimen intensity. Table 2 compares the effect of TBI- and non-TBI containing MAC and RIC regimens adjusted for age, HCT-CI, recipient CMV serostatus, disease, DRI and graft type. NRM risks were higher after RIC non-TBI compared to RIC TBI regimens. The predominant RIC non-TBI regimen was Flu/Mel (100mg/m2) ± TT (5mg/kg). In conclusion, a MAC regimen offers higher disease-free survival for those aged 18-54 years and can tolerate MAC regimens. For patients who are unable to tolerate MAC regimens, regardless of their age, TBI200 cGy/Cy/Flu is preferred to Flu/Mel ± TT to minimize NRM risks. [Display omitted] DisclosuresShah:Juno Pharmaceuticals: Honoraria; Lentigen Technology: Research Funding; Exelexis: Equity Ownership; Geron: Equity Ownership; Miltenyi: Other: Travel funding, Research Funding; Oncosec: Equity Ownership. Brunstein:Gamidacell: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Hamadani:Celgene Corporation: Consultancy; Merck: Research Funding; Janssen: Consultancy; ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Cellerant: Consultancy; Takeda: Research Funding; Ostuka: Research Funding; MedImmune: Consultancy, Research Funding. McGuirk:Gamida Cell: Research Funding; Kite Pharma: Honoraria, Other: travel accommodations, expenses, speaker ; Fresenius Biotech: Research Funding; Pluristem Ltd: Research Funding; Bellicum Pharmaceuticals: Research Funding; Astellas Pharma: Research Funding; Novartis Pharmaceuticals Corporation: Honoraria, Other: speaker, Research Funding. Vasu:Boehringer Ingelheim Inc: Membership on an entity's Board of Directors or advisory committees. Waller:Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Cambium Medical Technologies: Consultancy, Equity Ownership; Celldex: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kalytera: Consultancy.

Real-World Outcomes of Older Patients with Primary Central Nervous System Lymphoma (PCNSL): Methotrexate Dose Intensity and Combination with Cytarabine Correlate with Response and Survival

INTRODUCTION Primary central nervous system lymphoma (PCNSL) in patients (pts) over 65 years old have poorer outcome compared to younger cohorts, as comorbidities, baseline performance status and susceptibility to iatrogenic toxicity impede adequate drug delivery (Kasenda et al, Ann Oncol, 2015). Balancing toxicity against treatment benefits remains a challenge in this age group. Recent trials have attempted to rationalize treatment aiming for reduced toxicity whilst maintaining CNS penetration. Efficacy of additional agents, such as oral alkylators (Fritsch et al, Leukemia 2017) has also been demonstrated. Most clinical trial cohorts underrepresent elderly pts and thus analysis of real-world outcomes and therapeutic practice is warranted. METHODS Consecutively diagnosed pts between 01/10/12 and 01/10/17, ≥65 years old in 14 tertiary UK centres were analysed retrospectively. Radiological exclusion of systemic disease and histological diagnosis were mandatory. Pts receiving any form of 1st line treatment including palliative (whole-brain radiotherapy [WBRT]/oral chemotherapy), best supportive care (BSC) or clinical trial were included. Diagnostic and referral pathways were audited. Baseline patient characteristics and treatment received was recorded in order to document current UK practice. Pts. were stratified into 4 treatment groups: single agent MTX; MTX with oral alkylator; high-intensity HI-MTX (MTX/AraC and MATRix) or palliative intent treatment (WBRT/oral alkylator/BSC). The study primary outcome was overall response rate (ORR) after induction. Secondary outcomes were PFS and OS. Additional variables were MTX clearance and the relative dose intensity (RDI) of MTX normalised with a reference of 14mg/m2. UV/MVA for ORR and Cox-regression for PFS and OS were used for identification of baseline predictors of response and survival. RESULTS 244 pts were included in the analysis with median age 71yrs (range 65-91) and 123 (50%) male. LDH (Elevated:104, 42%) and ECOG performance score (PS) (3-4: 87, 36%) were the only prognostic markers recorded. Median time from presenting scan to treatment was 33 days (IQR 22-48). Demographic characteristics are summarised in table 1. 80% of pts (n=192) received MTX based chemotherapy. 68% of pts >70yr and 50% >75yr received >1 cycle of MTX. MTX median cumulative dose delivered was 10.6 g/m2 (range 1.5-21), median number of cycles was 4 (range 1-6). Dose reductions of MTX occurred in 53/176 pts. (30%). Median time to MTX clearance was 3 days (range 1-18) and median RDI was 0.75 (range 0.11-1.5). TRM for MTX treated pts was 7.2%. 112 pts received rituximab (46%; 11% pre-2015 vs. 64% post-2015). 73 pts. (38%) received ORR after induction was 63%. HI-MTX (HR 3.4; CI 95% 1.5 - 7.6; p=0.003) was independently associated with superior ORR compared to HD-MTX alone (Table 1). Median follow up for survival was 25 months. 2-yr PFS and OS were both 39%, median OS after progression was 80 days. MTX RDI (HR 0.18; p 52 pts (21%) received upfront palliative treatment and compared to MTX cohort, were older (median 76y vs. 70y), had a poorer PS (ECOG 3-4: 62% vs. 28%) and higher incidence of impaired renal function (GFR CONCLUSION MTX can be delivered to the majority of pts >70 years with manageable TRM rates. Notably, early treatment discontinuation was relatively frequent with outcomes in this group comparable to palliative care. By contrast, pts who completed >3 cycles of HI-MTX and underwent consolidation experienced comparable outcomes to younger trial cohorts. MTX combination chemotherapy and MTX dose intensity were the strongest predictors of survival whilst rituximab was not a covariate for response or survival despite an increase in its use. Maximising cumulative MTX dose, particularly within more intensive protocols, may translate into improved ORR and survival in older pts with PCNSL. Disclosures Kassam:AbbVie: Equity Ownership. Culligan:Merck Sharp & Dohme (MSD): Honoraria; Celgene: Other: Support to attend conferences; Daiichi-Sankyo: Other: Support to attend conferences; JAZZ: Honoraria; Abbvie: Other: Support to attend conferences; Takeda: Honoraria, Other: Support to attend conferences; Pfizer: Honoraria. McKay:Epizyme: Consultancy, Honoraria. Eyre:Roche: Consultancy; Janssen: Consultancy, Other: travel support; Gilead: Consultancy, Other: travel support; Abbvie: Consultancy, Other: travel support; Celgene: Other: travel support. Osborne:Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Servier: Consultancy; MSD: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Other: Travel to conference. Yallop:Servier: Other: Travel funding; Pfizer: Consultancy. Fox:Janssen: Consultancy, Other: Personal fees and non-financial support, Speakers Bureau; AbbVie: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Other: Travel support, Speakers Bureau; Sunesis: Consultancy; Roche: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Other: Travel support, Research Funding, Speakers Bureau. Cwynarski:Roche: Consultancy, Other: Conferences/Travel support, Speakers Bureau; Autolus: Consultancy; Kite: Consultancy; Gilead: Consultancy, Other: Conferences/Travel support, Speakers Bureau; Janssen: Other: Conferences/Travel support.

Results from REACH1, a Single-Arm Phase 2 Study of Ruxolitinib in Combination with Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Vs-Host Disease

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with high-risk or relapsed hematologic malignancies. Development of acute graft-vs-host disease (aGVHD) is a risk factor for nonrelapse mortality after allo-HSCT. Systemic corticosteroids (CS) are recommended first-line treatment for aGVHD, but Methods: REACH1 was an open-label, single-cohort, multicenter, phase 2 study. Eligible pts were ≥12 years old, had an allo-HSCT from any donor source for hematologic malignancies, developed grade II-IV SR aGVHD per Mount Sinai Acute GVHD International Consortium criteria, and had ≤1 systemic treatment in addition to CS for aGVHD. SR aGVHD was defined as GVHD that progressed after 3 days or had not improved after 7 days of primary treatment with methylprednisone ≥2 mg/kg/d (or equivalent), development of GVHD in another organ after receiving CS (≥1 mg/kg/d methylprednisone) for skin or skin plus upper gastrointestinal GVHD, or inability to tolerate CS taper. Pts received RUX 5 mg twice daily (BID), with optional increase to 10 mg BID in the absence of cytopenias. The primary endpoint was overall response rate (ORR) at Day 28, defined as the proportion of pts having complete response (CR), very good partial response, or partial response (PR). The key secondary endpoint was 6-month duration of response (DOR; time from first response to GVHD progression or death). Results: At the primary analysis of ORR (02 Apr 2018), 71 pts received ≥1 dose of RUX. Mean (range) age was 52.9 (18-73) years; 49.3% of pts were men. Acute myeloid leukemia (AML) and myelodysplastic syndrome were the most common primary malignancies (28.2% each). Most pts (80.3%) received peripheral blood stem cells; 18.3% received bone marrow, and 1.4% received cord blood as the stem cell source. Treatment was ongoing in 17 pts (23.9%) at data cutoff. At baseline, 23 pts (32.4%) had grade II aGVHD, 34 (47.9%) had grade III, and 14 (19.7%) had grade IV; 36 pts (50.7%) had ≥2 organs involved. Before starting RUX, 19 pts (26.8%) had progressive aGVHD after 3 days of CS treatment, 30 (42.3%) had no response after 7 days of CS, 8 (11.3%) developed new organ involvement on CS Table 1 ). Median DOR among Day 28 responders has not been reached (lower limit, 159 days; Figure 1 ). Event-free probability estimates (95% CI) for Day 28 responders at 3 and 6 months were 79.0% (62.3%-88.9%) and 67.0% (47.3%-80.7%), respectively. Best ORR at any time was 73.2% (CR, 56.3%). Median (range) time to response was 7.0 (6-49) days. Two pts had malignancy relapse (AML in both). At Day 28, 43 pts were on RUX and CS treatment; 55.8% (24/43) of these pts had a 50% reduction from baseline in CS dose ( Figure 2 ). Most pts (69/71) initiated RUX at 5 mg BID. At Day 28, 46.5% of pts (20/43) received RUX 10 mg BID. The most common treatment-emergent adverse events (TEAEs; any grade, grade 3/4) were anemia (60.6%, 46.5%), hypokalemia (47.9%, 18.3%), decreased platelet count (43.7%, 38.1%), peripheral edema (43.7%, 11.3%), and decreased neutrophil count (36.6%, 31.0%). Cytomegalovirus (CMV) infection, viremia, and chorioretinitis occurred in 9 (12.7%), 4 (5.6%), and 1 (1.4%) pts, respectively (43.7% of pts were CMV+ at baseline). Fatal treatment-related TEAEs were sepsis and pulmonary hemorrhage (1 pt each) and were attributed to both RUX and CS. Conclusion: In this first prospective trial of RUX in pts with SR aGVHD, RUX treatment resulted in overall responses in 54.9% of pts with SR aGVHD by Day 28, many of whom (68%) had grade III/IV disease at baseline. Best ORR at any time was 73.2% (CR, 56.3%). Responses were rapid and durable. Most pts achieved sustained reductions in CS dose. The AE profile was consistent with expectations for RUX and pts with SR aGVHD. RUX represents a promising therapeutic strategy; a phase 3 trial of RUX vs best available therapy in SR aGVHD is underway. Disclosures Jagasia: Incyte Corporation: Membership on an entity9s Board of Directors or advisory committees. Perales: Merck: Other: Personal fees; Abbvie: Other: Personal fees; Takeda: Other: Personal fees; Novartis: Other: Personal fees; Incyte: Membership on an entity9s Board of Directors or advisory committees, Other: Personal fees and Clinical trial support. Schroeder: Incyte Corporation: Membership on an entity9s Board of Directors or advisory committees. Ali: Incyte Corporation: Membership on an entity9s Board of Directors or advisory committees. Shah: Lentigen Technology: Research Funding; Miltenyi: Other: Travel funding, Research Funding; Juno Pharmaceuticals: Honoraria; Geron: Equity Ownership; Exelexis: Equity Ownership; Oncosec: Equity Ownership. Chen: Magenta Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy; Incyte: Consultancy, Membership on an entity9s Board of Directors or advisory committees; REGiMMUNE: Consultancy. Arbushites: Incyte Corporation: Employment, Equity Ownership. Dawkins: Incyte Corporation: Employment. Tian: Incyte Corporation: Employment. Khoury: Incyte Corporation: Membership on an entity9s Board of Directors or advisory committees, Research Funding.

Graft-Versus-Host Disease (GVHD) Prophylaxis with Post-Transplant Cyclophosphamide (PTCY) Induces a More Tolerant Immune Response after Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) in Patients Previously Exposed to Nivolumab

Allo-HCT has been shown to be feasible in patients previously exposed to anti-PD-1 monoclonal antibodies, albeit their use has been associated with a more frequent and more severe acute GVHD. Our aim was to study the effect of pre-transplant exposure to the anti-PD1 nivolumab on early immune response after allo-HCT and how this response becomes modulated by the use of PTCY.Twelve patients diagnosed with lymphoproliferative neoplasms who underwent an allo-HCT from HLA matched related or unrelated donors were analyzed. Considering pre-HCT exposure to nivolumab and type of GVHD prophylaxis, patients were classified into 4 groups: previous nivolumab and GVHD prophylaxis with PTCY (Nivo-PTCY, n=3), previous nivolumab and standard GVHD prophylaxis with tacrolimus and sirolimous (Nivo-TacSiro, n=3), no previous nivolumab and GVHD prophylaxis with PTCY (Control-PTCY, n=3) and no previous nivolumab and standard GVHD prophylaxis (Control-TacSiro, n=3). Patients exposed to nivolumab received a median of 8.5 (range 4-16) doses at 3mg/Kg, being the median time from the last dose of nivolumab to allo-HCT of 84 (range, 34-154) days. With a median of 29 (range 23-37) days, all 3 patients in the Nivo-TacSiro group experienced fatal grade 3-4 acute GVHD. No other grade 3-4 GVHD was observed in the other patients and only 2 (1 in each control group) had grade 2 acute GVHD. All 12 patients were in full-donor chimera on day +21. Concentration of nivolumab in plasma was measured on Day 0 (allo-HCT), +7, +14, +21, +28 and +56 by ELISA. Early immune response on day +21 was assessed by flow cytometry analyzing changes in the T-cell repertoire, variations on the expression of PD-1 and other inhibitory receptors (TIM-3 and LAG-3), and modifications in the myeloid compartment.Residual nivolumab was detected as late as 56 days after allo-HCT in the plasma from all 6 patients exposed to the drug (Figure 1A). In addition PD-1 expression on CD4+ and CD8+ T cells on day +21 was found to be lower in these patients compared to control groups, pointing out that residual nivolumab was able to block PD-1 on donor-derived T-cells after allo-HCT (Figure 1B). We then analyzed the effect of pre-transplant nivolumab on early (day +21) immune response after allo-HCT by comparing groups of patients with the same GVHD prophylaxis. Hence, patients in the Nivo-TacSiro subgroup presented a lower CD4+/CD8+ ratio, lower counts of naïve CD8+ T cells (Figure 1C), higher percentage of IFN-γ-producing CD4+ and CD8+ T cells, lower expression of TIM-3 on CD4+ an CD8+ T cells as well as promotion of Th1 differentiation after allo-HCT than Control-TacSiro patients. Also, these patients had a higher proportion of classical monocytes and higher expression of the activation marker CD86 than patients not exposed to anti-PD1 (Figure 1D). All this immune activation was in line with the clinical scenario of severe GVHD observed later on in the 3 patients of the Nivo-TacSiro subgroup. Conversely, patients in the Nivo-PTYC subgroup had similar proportions of T-cell subpopulations (especially in the CD8 compartment), Th1 differentiation, and monocyte profile at day +21 than patients in the Control-PTYC subgroup, indicating that previous nivolumab exposure has little influence on the effect of PTCY. Finally, a direct comparison of the two GVHD prophylaxis schemes used in the 6 patients previously exposed to nivolumab revealed that Nivo-PTCY patients had a higher CD4+/CD8+ ratio, higher proportion of CD4+ and CD8+ effector memory T-cells (Figure 1C), lower percentage of IFN-γ-producing T cells, as well as an attenuated Th1 response and a lower proportion of classical monocytes (Figure 1D) after allo-HCT compared with Nivo-TacSiro patients.In conclusion, pre-transplant nivolumab is detectable in plasma of patients within 2 months following allo-HCT and it seems to be responsible for an altered early T-cell and monocyte activation status in patients receiving standard GVHD prophylaxis. PTCY seems capable of inducing a more tolerant profile of immune cells in patients previously exposed to nivolumab. Therefore, the use of PTCY as GVHD prophylaxis in patients previously exposed to immune checkpoint inhibitors warrants further investigation. [Display omitted] DisclosuresIacoboni:Roche: Honoraria; Celgene: Other: Travel funding.

MIPSS70+ V2.0 and Revised Cytogenetics Changes Predict Outcomes of Allogeneic Transplantation with Fludarabine and Melphalan Conditioning in Patients with Myelofibrosis

Several prognostic models have been developed to predict survival outcomes and response in patients with myelofibrosis (MF). MIPSS70 prognostic system, developed by incorporation of all the key clinical characteristics, cytogenetics, and mutational factors into one system, has recently been revised to MIPSS70+ v2.0 with refinements in degrees of anemia, cytogenetics, and HMR. While allogeneic hematopoietic cell transplantation (alloHCT) is the only curative treatment for patients with MF, limited data exists on the impact of molecular markers on transplant outcomes. Here, we evaluated the transplant outcome in MF patients who uniformly received fludarabine/melphalan (FluMel) conditioning at City of Hope and assessed the impact of cytogenetics, somatic mutations on transplant outcomes based on a 72 gene next-generation sequencing (NGS) panel and MIPSS 70+ v2.0.A total of 110 consecutive MF patients (primary: n=58, secondary: n=52) without prior acute leukemic transformation, underwent alloHCT between 2004 and 2017. Median age at the time of transplant was 58.5 years (range: 38-72 years) with median interval from diagnosis of primary or secondary MF to HCT of 15.2 months (range: 1.6-332.5 months). AlloHCT donors were matched related (n=51), matched unrelated (n=44), and mismatched unrelated (n=15). Intermediate-2 and High risk by DIPSS accounted for 83 (76%) of patients at the time of transplant. Tacrolimus/Sirolimus-based GVHD prophylaxis was used in 100 (91%) patients, and 16 had splenectomy prior to alloHCT.Pre-transplant DNA sample were available for 93 patients and cytogenetics information was available for 106 patients; among which 60 had abnormal cytogenetics. Based on recently developed revised cytogenetic risk stratification on transplant outcomes, we identified 67 patients (61%) in favorable, 24 (22%) in unfavorable, and 15 (14%) in very high risk groups. Median number of 2 mutations were detected with at least one mutation in 95% (n=88) of patients. JAK2 V617F was the most common alteration noted in 54 (58.1%) patients. Other common mutations were ASXL1 (n=41, 44%), CALR type 1 (n=15, 16.1%), TET2 (n=12, 13%) SRSF2 and DNMT3A (each n=10, 11%). No detectable mutations were found in 5 (5.4%) patients. HMR genes (ASLX1, EZH2, IDH1/2, SRSF2, and U2AF1) were identified in 48 patients (52%), with 30 patients (32%) carrying one and 18 patients (19%) carrying more than 1 HMRs.With a median follow-up of 63.7 months (range: 11.9-158.5), 5 year overall survival (OS) and non-relapse mortality (NRM) were 65% (95% CI: 54-73) and 17% (95%CI: 10%-24%), respectively. Detailed transplant outcomes were previously reported (Ali et al. American Society of Hematology. Vol. 130. Atlanta, GA: Blood; 2017:199) (Figure 1a). On multivariable analysis, unfavorable and VHR cytogenetic changes had significantly shorter OS and PFS (p=0.001 and 0.008), and relapse risk (p=0.035) (Figure1b). Triple negative status (p=0.063), HMR (p=0.73), and more than 1 HMR (p=0.59) did not significantly impact survival post-HCT. (Figure1c) Similarly, CALR type 1 (p=0.42), and ASXL1 (p=0.29) mutations also did not impact survival after HCT. Only CBL mutation was significantly associated with lower OS (HR=2.64, 95% CI: 1.09-6.38, p=0.032) and lower DFS (HR=4.35, 95% CI: 1.83-10.36, p<0.001), largely attributable to increased NRM (HR=3.68, 95% CI: 1.45-9.35, p=0.004). In addition U2AF1 mutations were significantly associated with NRM (HR=3.42, 95%CI: 1.50-7.80, p=0.009). Per MIPSS70+ 2.0, patients were classified into intermediate (n=11), high (n=47), or very high-risk (VHR) (n=35). MIPSS70+ 2.0 predicted OS, DFS, and NRM. Compared to high risk group, intermediate risk patients had better OS (HR=0.291, 95% CI: 0.04-2.26) and DFS (HR=0.24, 95% CI: .03-1.91), whereas VHR group had much lower OS (HR=5.05, 95% CI: 2.39-10.74, p=<0.001) and DFS (HR=3.87, 95% CI: 1.9.0-7.88 p<0.001). (Figure 1d) Compared to high risk, intermediate risk group had lower and VHR had higher NRM (HR=0.51, 95% CI: 0.06-4.23), and (HR=3.24, 95% CI: 1.47 - 7.13, p=0.004), respectively.In summary, we are presenting one of the largest single center experiences of FluMel-based alloHCT for MF patients, demonstrating revised cytogenetic changes and MIPSS70+ v2.0 accurately predicts transplant outcomes, thus would better inform physicians and patients in discussing and decision making about alloHCT. [Display omitted] DisclosuresAli:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Khaled:Juno: Other: Travel Funding; Alexion: Consultancy, Speakers Bureau; Daiichi: Consultancy. Salhotra:Kadmon Corporation, LLC: Consultancy. Stein:Amgen Inc.: Speakers Bureau; Celgene: Speakers Bureau. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Venetoclax As Monotherapy or in Combination: Patterns of Use and Predictors of Outcomes in an International Multicenter Study of CLL Patients

Venetoclax As Monotherapy or in Combination: Patterns of Use and Predictors of Outcomes in an International Multicenter Study of CLL Patients

Adverse Events, Patterns of Tumor Lysis Syndrome Prophylaxis and Management, and Dosing Patterns in a Large Cohort of Venetoclax Treated CLL Patients in Community and Academic Settings

Adverse Events, Patterns of Tumor Lysis Syndrome Prophylaxis and Management, and Dosing Patterns in a Large Cohort of Venetoclax Treated CLL Patients in Community and Academic Settings