Allo SCT Research Articles

Effect of pre-transplant functional status on length of hospital stay in patients undergoing allogeneic hematopoietic stem cell transplant in an outpatient transplant program.

6560 Background: The use of reduced intensity conditioning regimens including non-myeloablative regimens in allogeneic hematopoietic stem cell transplant (allo SCT), has expanded the pool of transplant candidates in the United States. Nonetheless, allo SCT, is associated with significant morbidity and mortality especially in patients 65 and older. In our outpatient transplant program, allo SCT patients undergo a comprehensive physical and occupational therapy (PT/OT) evaluation pre-transplant. Methods: We retrospectively reviewed all patients undergoing an allo SCT between January 2019 and December 2022 who had a PT/OT evaluation pre-transplant. We analyzed lower extremity functional scale (LEFS) and fatigue score (FACIT). The FACIT score is a patient reported outcome tool where the lower the score, the less fatigue impacts a patient’s performance. Results: We identified 218 patients who had at least one variable reported. Eighty-one patients were 65 years of age or older. All patients in the 65 and older group had a RIC or NMA conditioning regimen. In the 65 and older group, 72.8% had an HCTCI score of 3 or more compared to 59.1% in the group younger than 65. In patients younger than 65, those who had a lower LEFS (ie less lower extremity strength), had a statistically significant longer hospital stay of 15.5 days compared to 9 days (p=0.003). In patients 65 and older, lower FACIT scores (ie less patient reported fatigue), resulted in a statistically significant shorter hospital stay of 7.5 days compared to 13 days (p=0.019). In addition, there was a trend towards shorter hospital stays in patient 65 and older who had a higher LEFS of 5 days compared to 12.5 days (p=0.07). There was no difference in survival outcomes but there was a trend towards better overall survival in patients 65 and older with high LEFS (p=0.08) and a trend towards better NRM in this group (p=0.11). Conclusions: Our study highlights the need for comprehensive assessments in patients undergoing allo SCT. Geriatric functional status assessments are necessary to determine patients at risk for complications and to optimize such patients with exercise and cognitive rehabilitation programs prior to allo SCT. [Table: see text]

Academic Outreach and Collaboration with Community Oncology Practices to Enhance Referrals and Reduce Disparities in Hematological Malignancies

Introduction: Disparities in cancer care are widely reported with the reasons being multifactorial. Delays in referral and distance to travel along with lack of public transportation are common structural barriers that further exacerbate the racial and income related disparities in the care of hematological malignancies. A lower proportion of black patients receive transplants, both autologous (AutoSCT) and allogeneic (AlloSCT) for similar indications as compared to white populations. Racial disparities are evident in transplant utilization for hematologic malignancies. When offered similar therapy, the outcomes might be better in black patients as compared to White populations underscoring the effect of biology of the disease. South Georgia region has a very high poverty rate with many counties having a median income much less than the national average. We report our efforts to increase access for hematological malignancies for patients in predominantly rural and minority focused settings. Methods: We reviewed charts of all patients referred to our center from 01/2014 to 12/2022. We divided patients into three groups. Cohort A. 36 months from 1/14 to 06/2017. Cohort B, 36 months from 07/19 to 12/22. The intervening two years were utilized for outreach development. Physicians visited all the community centers and created an easy access physician to physician referral system. In addition, in partnership with community oncology, two clinics were established at 65 miles and 89 miles to our center. Referrals from these sites were seen at these outreach clinics. The total number of Auto and Allo SCT and clinical trial enrollment data were obtained from databases. Outcomes data is from that reported on the SCT patients to the national databases. Statistics are descriptive. Results: Post outreach activity showed a significant increase in volumes. (Figure 1) Patients' referrals for heme-malignancies were up to 1725 compared to 632 (170% increase). The median distance travelled in these groups was 52.7 vs 17.8 miles (range 0-525 vs 2342) demonstrating the larger area covered from outreach activity. Considering our metro area radius of 20 miles, 62% of patients were outside our immediate area. Excluding the patients withing the 20-mile radius between the two groups, median distance travelled by patients in cohort B being 99 miles vs 60 miles in cohort A. The increase was consistent across all races. There was an increase from 254 to 588 in black population and 355 to 1028 in the white populations. The outreach clinics set up in partnership with the community practices added a significant new patient population with numbers increasing from under 25 in the initial cohort to above 250 in cohort B. Overall this increase translated to higher number of transplants with 146 transplants in cohort A compared to 347 in cohort B, a 137% increase. The alloSCT increased from 51 to 85 and autoSCT from 95 to 262 between the two cohorts respectively. In addition, the addition of CAR-T further expanded the cellular therapy program with a total of 131 cellular therapy products in fiscal year 2023 compared to 39 in fiscal year 2015, a 235% increase. Our outcomes have consistently improved as well with the most recent CIBMTR 1 year survival of 74% while the predicted was 68%. Similarly, the increase in referrals translated to an increase in clinical trial enrollment with the most recent 3-year period having an accrual of 216 as compared to 56, a 285% increase overall and 185% in black patients, compared to the initial 3 years. Age is another commonly noted factor that results in lower access to care. Our model resulted in a significant increase in elderly patients as well with > 60 years of age patients increasing from 326 to 1017 while those above 70 increased from 149 to 549 in the respective cohorts. Conclusions: Our model is easily reproducible and shows a substantial increase in the number of referrals for hematological malignancies. The recent approvals of complex therapies like CAR-T and other T cell engaging therapies necessitate a close collaboration between academic and community practices. Similar models if developed at other academic centers can significantly reduce structural barriers and might improve outcomes further in all patient populations.

Age-Adapted Chemotherapy for Adults >40 Years Old with Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia: Single Center Outcomes

Introduction: While pediatric-inspired regimens are preferred in younger adults with Ph-negative ALL, the optimal approach for treating adults age >40 with Ph-negative ALL has not yet been defined. In the U.S., hyperCVAD-based regimens are commonly used in this age group; however, hyperCVAD may be less effective than pediatric-inspired regimens in patients who are appropriate candidates for intensive therapy, and may be excessively toxic in patients who are poor candidates for intensive therapy. We explored giving two different multiagent chemotherapy regimens to adults age >40 with newly diagnosed Ph-negative ALL, depending on the individual patient's age and fitness level. Methods: At our institution starting in September 2020, patients between 40-60yo with good performance status received an intensive pediatric-inspired regimen based on the CALGB 10403 backbone, while patients >60yo (or 50-60 with poor PS) received a moderate-intensity multiagent chemotherapy backbone consisting of 2-part induction (induction-1: infusional doxorubicin/vincristine D1-4 + dexamethasone 40mg D1-4, 9-12, 17-20; induction-2: same as induction-1 plus cyclophosphamide 1000mg/m 2 on day 1) and consolidation with 6 cycles of chemotherapy, alternating between methotrexate (1g/m 2) plus peg-asparaginase (1,000U/m 2), and cytarabine (1g/m 2 x 6 doses). Prior to September 2020, patients in this age group received the hyperCVAD backbone. In both cohorts, patients not proceeding to allogeneic SCT in CR1 received POMP maintenance for up to 2 years. We reviewed charts of patients aged >40 with newly diagnosed Ph-negative ALL at University of Colorado Hospital from 2014-2023 to compare outcomes between patients treated before 09/2020 (“hyperCVAD” cohort) and after 09/2020 (“age-adapted” cohort). Results: Between 09/2020-04/2023, 17 adults with median age of 57 (range 40-81) with newly diagnosed Ph-negative ALL began treatment at our institution. 6 patients (age 40-56) received a modified pediatric-inspired regimen, and 11 patients (age 54-81) received a moderate-intensity regimen. 4 patients underwent allogeneic SCT in CR1 (including 1 for tMDS that developed during maintenance therapy). 3 patients received blinatumomab in CR1, 2 of whom subsequently received allo SCT. With a median follow-up of 16 months (range: 1-32 months), 1 patient relapsed during maintenance and 2 patients died from treatment-related mortality (1 during induction chemotherapy, 1 during salvage therapy for primary refractory disease). All three events occurred in patients who received the moderate-intensity regimen. Grade 3 or 4 asparaginase-related toxicities occurred in 2 patients (1 gr3 hyperbilirubinemia, 1 gr3 pancreatitis) and both resolved with supportive care. Between 2014-2020, 18 adults with median age of 58 (range 42-80) received hyperCVAD for newly diagnosed Ph- ALL. 6 patients received allogeneic SCT in CR1, and no patients received blinatumomab in CR1. With a median follow-up of 31 months (range: 7-94 months), 7 patients relapsed during consolidation or maintenance therapy and 3 relapsed after SCT. Among 10 patients who died during follow-up, 7 deaths were due to relapsed/refractory disease and 3 were due to treatment-related mortality (all 3 TRM were post-transplant). An improvement in relapse-free survival is seen in the cohort treated with age-adapted chemotherapy vs. the hyperCVAD cohort (p=0.045, log-rank test) (Figure 1), while there was no difference in overall survival (p=0.29) (not shown). Conclusions: Age-adapted multiagent chemotherapy is safe and effective in adults age >40 with Ph-negative ALL and may result in better outcomes than hyperCVAD. This is possibly due to better efficacy of pediatric-inspired chemotherapy for younger (40-60yo) patients and better tolerability of moderate-intensity chemotherapy for older (>60yo) patients, compared to hyperCVAD. Broad use of asparaginase in both the pediatric-inspired and moderate-intensity regimens may have also contributed to better outcomes in comparison to hyperCVAD. Incorporation of novel therapies in the frontline setting holds much promise to improve outcomes for older adults with Ph- ALL. Our observations suggest that the specific multi-agent chemotherapy regimen used, and in particular the incorporation of peg-asparaginase, may also affect outcomes significantly.

“Dose-Dense” Mini-Hyper-CVD, Inotuzumab Ozogamicin and Blinatumomab Achieves High Rates of Rapid MRD-Negativity in Patients with Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia: A Retrospective Analysis

Background: Mini-hyper-CVD plus inotuzumab ozogamicin (InO) followed by sequential blinatumomab (Blina) is effective in both older adults with newly diagnosed B-cell ALL and in relapsed/refractory disease. We hypothesized that concomitant administration of these agents in a “dose-dense” (DD) fashion would also be safe and effective in B-cell acute lymphoblastic leukemia (ALL), leading to rapid measurable residual disease (MRD) negativity. Methods: This is a retrospective analysis of patients (pts) with B-cell ALL who received DD mini-hyper-CVD + InO + Blina outside of a clinical trial. All pts received mini-hyper-CVD alternating with mini-methotrexate and cytarabine in combination with InO. To be evaluable for this analysis, Blina must have started prior to day 21 of the first cycle of therapy. Pts were included if they received this regimen for 1.) frontline induction, 2.) treatment of MRD-positive remission, or 3.) salvage therapy for relapsed/refractory (R/R) disease. Results: Between 7/2020 and 1/2023, 21 eligible pts were treated (Table 1 ). The median age was 48 years (range, 6-74 years); 3 pts (all in the R/R cohort) were <18 years old. 9 pts (43%) were treated as frontline therapy, 4 (19%) for treatment of MRD (3 for flow-positive MRD and 1 for persistent FISH for t[4;11]), and 8 (38%) for R/R disease. In the MRD cohort, 3 pts were in first CR and 1 was in second CR; 1 pt received prior InO and 1 had prior allogeneic stem cell transplant (alloSCT). In the R/R cohort, pts were heavily pretreated, with a median number of prior therapies of 3 (range, 1-7); 2 pts received prior InO, 3 pts received prior Blina, 3 pts had undergone prior allo SCT, and 3 pts had received prior chimeric antigen receptor T-cell (CAR-T cell) therapy. Three pts (all in the R/R cohort) had extramedullary (EM) disease, 2 outside of the CNS without marrow disease and 1 with CNS disease and bone marrow MRD by flow. Pts received a median of 2 cycles (range, 1-5) of a dose-dense regimen. All pts received 0.9 mg/m 2 InO in cycle 1, except for 1 pt in the R/R cohort who received 0.6 mg/m 2 due to myelosuppression with prior InO. Themedian cumulative dose of InO was 1.2 mg/m 2 (range, 0.6-2.7 mg/m 2). Blina was started on a median of day 4 (range, day 4-17) of the first cycle of chemotherapy. Blina was started by day 7 in 16 pts (76%). In the frontline cohort, all pts (100%) achieved CR/CRi (CR in 8 pt and CRi in 1 pt), all after cycle 1 ( Table 2). All pts in the frontline cohort achieved flow MRD negativity. 7 pts were evaluable for bone marrow next generation sequencing (NGS) MRD (sensitivity 10 -6). Of these, 4/6 (67%) achieved NGS MRD negativity after cycle 1, and all 7 evaluable pts (100%) achieved NGS MRD negativity. In the MRD cohort, all 3 flow-positive pts became flow MRD negative after cycle 1; the pt with positive FISH for t(4;11) became FISH-negative after cycle 2. 3 of the 4 pts in the MRD cohort (75%) became NGS MRD negative. Overall, 5 of the 8 pts (63%) in the R/R cohort achieved CR/CRi. Among 5 evaluable pts in the R/R cohort with marrow disease (including the pt with CNS disease and MRD-positive marrow), all achieved flow MRD negativity after cycle 1. Overall, 7 pts (33%) underwent consolidative alloSCT (2 in the MRD cohort and 5 in the R/R cohort), and 1 pt in the MRD cohort underwent consolidative CAR-T cell therapy. The treatment regimen was well tolerated. No patients developed sinusoidal obstruction syndrome/veno-occlusive disease. One pt had grade 1 CRS, and 2 pts had grade 1 tremor. With a median follow-up of 13.4 months (range, 0.5-20.6 months), 6 pts (29%) have died (1 in the frontline cohort, 1 in the MRD cohort and 4 in the R/R cohort). 3 deaths were due to complications of alloSCT, 2 were due to sepsis (1 in the setting of refractory leukemia and 1 during MRD-negative CR), and 1 from unknown cause. Among 18 responding pts, only 1 pt relapsed; the pt with MRD-positive t(4;11) by FISH relapsed 4.5 months after alloSCT. The median OS for the R/R cohort was 5.8 months and was not reached for the frontline or MRD cohorts. The 1-year OS rate for the frontline + MRD cohort was 83%. Conclusion: Dose-dense mini-hyper-CVD in combination with InO and Blina achieves rapid MRD-negative remissions in patients with B-cell ALL. All responding patients achieved flow MRD negativity after 1 cycle of therapy, with the majority also achieving NGS MRD negativity. This regimen is now being prospectively evaluated in an ongoing clinical trial in pts with R/R B-cell ALL and in older adults with newly diagnosed B-cell ALL.

Allogeneic (Allo-SCT) Versus Autologous Stem-Cell Transplantation (Auto-SCT) after Relapse to First Line Auto-SCT in Multiple Myeloma: A Meta-Analysis with Predominantly Individual Patient Data

PFS Introduction A second allogeneic transplantation (allo- SCT) in patients who relapse after first-line autologous transplantation (auto- SCT) is mentioned in a recent statement of the European Society for Blood and Bone Marrow Transplantation (EBMT) as a valuable clinical option, especially when novel immunotherapies such as bispecific antibodies or CAR -T cells are not available. However, it is still unclear whether allo- SCT achieves better results compared to auto-SCT in patients who relapse after first-line treatment with auto-SCT. Objectives To compare progression-free (PFS) and overall survival (OS) between allo-ASCT and auto-ASCT as second-line therapy in patients who relapsed after first-line therapy with auto-SCT by analyzing individual patient data and extracting results from published reports when individual patient data were not available. Methods We searched the electronic databases PubMed, EMBASE, and the Cochrane Library and Up to Date. The search was limited to English-language publications from 1995 to February 2022, and only 6 studies were found that met the requirements for comparing allo SCT and auto- SCT as second-line therapy for patients who had relapsed after the first Auto- SCT. Individual patient data on survival were available for 512 patients from the Japanese Society for Hematopoietic Cell Transplantation registry data (Ikeda T et al. Hematol Oncol 2019) and for PFS and OS for 289 patients from the CIMBMTR registry (Freytes CO et al., BMT 2014). For the other 3 studies, which included 170 patients, data were extracted from the original publications (Mehta J et al, BMT 1998, Qazilbash M et al, Cancer 2006, and Wirk B et al. J Clin Res 2013). We used standard meta-analysis techniques to calculate pooled estimates from random-effects models as incorporated in the software Review Manager V. 5 (The Cochrane Collaboration). Fixed-effect models used as sensitivity analyzes yielded similar results (data not shown). I² = [(Q - df)/Q] X 100%, where Q is the chi² statistic for heterogeneity and df is the degrees of freedom, in order to quantify inconsistency between study outcomes. Results All comparisons of included studies were retrospective in nature, with one study using a cross-case approach (Mehta J et al). Conditioning regimens used for allo-SCT varied between reduced-intensity conditioning (Freytes CO et al and Qazilbash MH et al) and ablative regimens (Mehta J et al). Our analysis was based on individual patient data from 801 patients and data from 170 patients from published reports. No data on PFS were available in the study by Ikeda T et al. The results showed a HR of 1.85 (CI, 1.49-2.22, p < 0.00001) for PFS in favor of the auto-SCT group (Figure 1A). No relevant heterogeneity was observed between reports (Chi² = 3.12, df = 3 (P = 0.37), I² = 3.8%). OS: Similar results were observed for overall survival with a HR of 1.91 (CI, 1.49-2.44, p < 0.00001) in favor of the auto-SCT group at relapse (Figure 1B). The test for heterogeneity showed marked heterogeneity between studies but, similar to PFS, did not reach statistical significance (Chi² = 6.28, df = 4 (P = 0.18), I² = 36.3%). Discussion and Conclusion The included studies showed some heterogeneity but the corresponding test did not reach a significance level. The main reasons for the differences between studies could be different ablative regimens and different patient characteristics. In some studies, the median age was lower in the Allo-SCT group, which favored it, a finding that was not observed in all comparative studies. Allo-SCT appears to benefit only a small proportion of patients with multiple myeloma, whereas graft-versus-host disease and infectious complications affect outcome in a much larger proportion of patients, resulting in a worse prognosis for the entire allo-SCT group. This scenario is supported by our analysis showing a statistically significant advantage of a second auto-SCT over allo-SCT in terms of PFS and OS in patients who relapse after first-line auto-SCT.

Long-term outcomes of allogeneic stem cell transplant in multiple myeloma

Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT (p = 0.03) and to have been transplanted between 2000 and 2010 (p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Allogeneic stem cell transplantation (alloSCT) was the only curative option for younger patients (pts) with relapsed/ refractory (r/ r) LBCL (DLBCL, tFL, PMBCL). Anti-CD19 CAR T-cells (CART) entered the clinical arena around 5 years ago now being considered standard of care for such patients. As >50% of LBCL pts progress or relapse after CART treatment we were interested in identifying prognostic factors for both modalities and their relative role in the treatment of advanced r/r LBCL. Methods: Pts registered with the EBMT database from 1/2016 to 5/2021 having received either a first alloSCT or commercially available CART therapy (Yescarta® or Kymriah ®) as ≥3rd therapy of LBCL were analyzed. To correct for imbalances in patient characteristics we did propensity score analyses considering only pts with complete information on IPI including LDH at the time of cell therapy. We performed multivariate analyses in patients with either low- or high-risk r/r LBCL according to LDH level at cell therapy in pts treated with alloSCT or CART. Results: We identified 515 pts with full information on IPI at cell therapy (212 alloSCT and 303 CART). Patient groups differed significantly in median age, IPI score, and disease status at cell therapy. Median follow up was 46.3 months after alloSCT and 22.1 months after CART treatment. In univariate analysis, type of cell therapy, disease status, and IPI at cell therapy had a significant impact on OS. Amongst IPI risk factors LDH, performance status, and number of extranodal sites had a significant impact on OS, PFS an RI. At 24 months, OS was 41% after allo SCT and 49% after CART. In a propensity score analysis using all IPI factors as covariates, CART was superior to alloSCT in terms of OS (HR 0.62, 95% CI: 45–0.84, p = 0.0193) but not PFS, RI or NRM. In multivariate analysis patients with IPI (o-2) low risk at cell therapy show better OS (HR 0.81, 95% CI 0.59–1.1, p < 0.0001) and PFS (HR 0.62, CI: 0.46–0.83, p = 0.00145), comparable RI and lower NRM (HR 0.21 CI: 0.11–0.42, p = 0.00001) with CART compared to allo SCT. In IPI (3–5) high-risk patients, CART showed significantly higher RI (HR 1.45, CI: 1.03–2.04, p = 0.03549) but lower NRM (HR 0.21, CI: 0.11–0.42), p = 0.00001) compared to allo SCT. OS and PFS did not significantly differ. Refractory disease was an independent adverse prognostic factor for OS (HR 1.74, CI: 1.3–2.33, p = 0.0002), PFS (HR 1.61 CI: 1.23–2.1, p = 0.0006) and RI (HR 1.79 CI: 1.29–2.49, p = 0.0006) but not for NRM. Results at 2 years are given in Table 1. Conclusion: IPI assessed at cell therapy is of prognostic impact for both CART and allo SCT. Overall, pts given CART for ≥3rd line treatment of DLBCL showed better OS than pts treated with alloSCT. In patients with high intermediate/high IPI results of CART must be improved and allogeneic SCT remains a valuable treatment strategy due to its high anti-lymphoma activity. Keyword: Cellular therapies Conflicts of interests pertinent to the abstract. B. Glass Consultant or advisory role: Kite, BMS, Novartis, Milteneyi, Roche, Janssen, Jazz, Abbvie Honoraria: Kite, BMS, Novartis, Milteneyi, Roche, Janssen, Jazz, Abbvie Research funding: Roche, Riemser A. Sureda Consultant or advisory role: Takeda, MSD, BMS, Novartis, Janssen, Roche, Sanofi, Gilead P. Dreger Consultant or advisory role: Kite, Novartis P. Corradini Honoraria: Abbvie, Amgen, Celgene, Giled, Incyte, Janssen, Takeda, R. Ram Honoraria: Novartis, Gilead, Takeda, BMS G. Wulf Consultant or advisory role: Gilead, Novartis A. M. García-Sancho Consultant or advisory role: Roche, BMS, Kyowa Kirin, Clinigen, Eusa Pharma, Novartis, Kite Gilead, Servier, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Kern M. Stelljes Consultant or advisory role: Medac, Pfizer, Jazz, Novartis, MSD, Amgen, BMS, Kite D. Blaise Consultant or advisory role: Jazz E. Forcade Consultant or advisory role: Gilead, Jazz, Novartis, GSK, Sanofi, MSD I. Hilgendorf Consultant or advisory role: Novartis, Abbvie J. A. Perez-Simon Consultant or advisory role: Novartis, Janssen, Gilead, Jazz, Alexion, Abbvie, Pfizer W. Bethge Consultant or advisory role: Gilead, Novartis, Miltenyi, Janssen, Celgene N. Schmitz Consultant or advisory role: Allogene Stock ownership: BMS Honoraria: Allogene Research funding: Janssen, Roche Educational grants: Allogene, Milteneyi

Effects of socio-economic status and gender on non-relapse mortality after allogeneic stem cell transplant.

e18600 Background: Allogeneic stem cell transplant (allo SCT) is a potentially curative therapy for hematological malignancies but is associated with high treatment related non-relapse mortality (NRM). Post-transplant care requires large amount of healthcare and patient resources, imposing higher burden on patients with lower socio-economic status (SES). Adverse health outcomes have been noted in males from lower SES background. We analyzed the effects of social factors on post-transplant survival and NRM in the diverse patient population treated at our institution. Methods: We retrospectively reviewed patients who underwent allo SCT at our program in 2015-2021. We collected baseline patient (demographics, KPS, HCT-CI), disease (diagnosis, risk index) and transplant characteristics (donor type, conditioning intensity). We extracted neighborhood level income data from US Census. Primary outcomes were survival and NRM. We used Fisher’s Exact, Wilcoxon Ranksum tests and logistic regressions. Results: 210 patients (116 males and 94 females) were included in the analysis. Neighborhood level estimated household income range was $26,041-163,074. Both 1 year OS and NRM, but not 100 days OS, significantly correlated with income. Patients who were alive at 1 year follow up (74.8% pts) had median income of $72K, compared to $62K for patients who died before 1 year (25.2% pts) and 60.5K for patients who died before 1 year without disease progression (13.3% pts) (p 0.032). The effect of income on NRM remained significant on multivariable analysis, adjusted for year of transplant, age, race, ethnicity, donor type, KPS, comorbidity index, regimen intensity, and disease risk. Increased conditioning intensity and haplo donor were also associated with increased 1 year NRM, while race and ethnicity did not have significant effect on 1 year NRM on multivariable analysis. The effect of income on NRM was dramatically different in male vs female patients. In men, a $10K increase in neighborhood income reduced the odds of NRM substantially (OR = 0.46, 95% CI 0.28-0.75), while in women there was no effect (OR 1.02, 95% CI 0.71-1.45). 1 year NRM in men was 9% vs 24% for higher vs lower neighborhood income (p 0.036), and in women 8% vs 13% (p 0.52). Conclusions: Our study identifies male patients residing in lower income neighborhoods as a subgroup at increased risk for NRM after allo SCT, after adjustment for the biological variables. The negative effects of lower neighborhood income and male gender become apparent with 1 year but not 100 days follow up, reflecting increasing difficulties with high resourses utilization over prolonged time period. Careful evaluation of controllable risk factors and optimizing social support may reduce the rate of complications. Further research into the factors mediating the relationship of neighborhood income with gender on survival and treatment-related mortality post allo SCT seems necessary.

Time-Sequential Change of the Predictive Power of Peripheral Blood WT1mRNA Levels after Allogeneic Stem Cell Transplantation for Myeloid Neoplasm Relapse and Development of a Dynamic Relapse Prediction Model

Introduction:Wilms tumor 1 messenger RNA (WT1mRNA) is detected in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), and is reportedly a useful minimal residual disease (MRD) marker. Allogeneic stem cell transplantation (allo-SCT) is the established cellular immunotherapy with a graft-versus-leukemia (GVL) effect and eliminates residual leukemia cells via the alloimmune response. The GVL effect is generally considered to occur after immune reconstruction. Therefore, the predictive power of WT1mRNA as an MRD marker for relapse may differ between the early and late periods after allo-SCT because the GVL effect is not expected in the early period without enough immune reconstruction. However, no studies have reported whether the predictive power of WT1mRNA for relapse changes in a time-sequential manner after allo-SCT. Hence, we investigated the relationship between WT1mRNA as a time-dependent variable and days after allo-SCT for AML/MDS relapse using a dynamic landmarking approach, and developed a dynamic relapse prediction model using the WT1mRNA level and measurement timepoint after allo-SCT. Methods: We retrospectively analyzed AML and MDS patients who received allo-SCT at Osaka Metropolitan University Hospital, and whose WT1mRNA levels were measured at least once from January 2008 to April 2021. WT1mRNA levels in peripheral blood were measured using an "Otsuka" WT1mRNA assay kit (Otsuka Pharmaceutical Co., Ltd.). Relapse was defined as hematological relapse or salvage chemotherapy intervention and/or donor lymphocyte infusion. To evaluate time-sequential changes in the predictive power of WT1mRNA for relapse and to develop a dynamic relapse prediction model, dynamic landmarking analysis was performed, which was reported by Hans C. van Houwelingen et al. The probabilities of the 1 year cumulative incidence of relapse (CIR) post-landmark timepoint were estimated with the Kaplan-Meier method. The Cox proportional hazard regression model was used to calculate the time-sequential hazard ratio for 1 year CIR not only post-landmark but also post-any timepoints after allo-SCT, and to develop a dynamic relapse prediction model. p < 0.05 was considered significant. Results: We analyzed 265 patients (AML: 197 and MDS: 68) and 2,539 WT1mRNA tests. Median patient age was 46 years, 55% of patients achieved complete remission at the time of allo-SCT, and the 2 year relapse-free survival rate was 46%. First, patients were divided into two groups, namely, those with WT1mRNA levels higher and lower than 200 copies/μg RNA, which is a previously reported cutoff value. Figure 1 shows a summary plot of the 1 year CIR of the two groups post-landmark timepoint. The 1 year CIR decreased over time after allo-SCT in the lower WT1mRNA group but not in the higher WT1mRNA group. The difference in 1 year CIR between the two groups increased over time after allo-SCT. Moreover, the hazard ratio of log WT1mRNA levels for 1 year CIR post landmark timepoints after allo SCT increased over time, and there was a significant interaction between WT1mRNA levels and landmark time (p < 0.001). These findings indicate that the predictive power of WT1mRNA levels for relapse increases over time after allo-SCT. Second, we developed a dynamic relapse prediction model that can predict the 1 year CIR post-any timepoint after allo-SCT based on individual post-transplant WT1mRNA levels and measurement timepoints. Figure 2 shows a time series of predictive values for 1 year relapse post-any timepoints derived from this prediction model, which assumed that WT1mRNA levels remain constant over time after allo-SCT. Conclusions: We demonstrated that the predictive power of peripheral blood WT1mRNA for relapse increases after allo-SCT over time. This finding implies that MRD in the early phase after allo-SCT is more likely to disappear owing to the GVL effect after immune reconstruction compared to one in the late phase. Transplant clinicians should pay attention to the difference in predictive power for relapse depending on the period when they observe elevated WT1mRNA levels. Dynamic landmark analysis also enabled prediction of continuous 1 year CIR post-any timepoint after allo-SCT by inputting the individual WT1mRNA level and measurement timepoint. Dynamic relapse prediction will offer useful information for clinical decision making. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

CART Therapy or Allogeneic Stem Cell Transplantation in ≥ Third Line Treatment of Large B Cell Lymphoma (LBCL)

Introduction: Allogeneic stem cell transplantation (alloSCT) was the only curative option for younger patients with LBCL (DLBCL, tFL, PMBCL) relapsing or being refractory to second-line therapy including high-dose chemotherapy and autologous SCT. After two commercially available CART products became available many pts are receiving CART third line. We sought to compare data from the EBMT registry focussing on the relative role of both treatment modalities in > third-line treatment of LBCL. Methods: Patients registered with the EBMT database from month 1/2016 to 5/2021 having received either a first alloSCT or commercially available CART therapy (Yescarta® or Kymriah ®) as ≥ third-line therapy of LBCL were analysed. To correct for imbalances in patient characteristics we did multivariate analyses considering only patient with complete information on IPI including LDH. Overall results in these patients and the population at large are identical. Results: We identified 1591 pts fulfilling the inclusion criteria (658 alloSCT, 933 CART); in 453 pts information on IPI and LDH at cell therapy was available (172 alloSCT and 281 CART). Patient groups differed significantly in clinical parameters as median age (50 yrs for alloSCT vs 62 yrs CART), median IPI score at cell therapy (1 in alloSCT and 3 in CART) and elevated LDH at cell therapy. The 1-year estimates for the major endpoints overall survival (OS), progression free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM) by the strongest prognostic factor LDH are given in the table below. In multivariate analysis, the type of cellular therapy (CART vs alloSCT) (HR 0.71 (95% CI.53-0.96, p=0.0237)) and LDH normal vs elevated (HR 0.58 (95%CI 0.44-077, p=0.00018)) significantly influenced OS, whilst age was not significant. Regarding RI, CART do significantly worse than allo SCT (HR 1.74 (95% 1.26-2.38, P=0.00067)); NRM was significantly lower after CART (HR 0.23 (95%CI 0,12-0.45, p< 0.0001)). Conclusion: Correcting for important confounding factors, pts given CART for ≥ 3rd line treatment of DLBCL still have better OS and PFS than pts treated with alloSCT. While CART therapy causes significantly less TRM, RI is generally higher than after alloSCT. Pts with active lymphoma (LDH >N, high IPI) prior to CART show high RI and a significant decrease in OS. This effect is less strong in allografted pts., Therefore, alloSCT remains a valuable option especially in patients with high-risk disease characterized by elevated LDH and high IPI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ALL-180 A Case of Refractory Philadelphia-Like Acute Lymphoblastic Leukemia Treated With Ruxolitinib/Blinatumomab and Ruxolitinib/Inotuzumab Ozogamicin Prior to Allogeneic Marrow Transplant

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subset associated with genomic alterations. These alterations can be grouped into major subclasses that either phenocopy BCR-ABL1 or activate JAK/STAT signaling. Ongoing trials suggest that patients harboring ABL-class fusions are candidates for ABL1 inhibitors, whereas alterations activating the JAK-STAT pathway may be amenable to treatment with JAK inhibitors. We hereby describe the first case of the use of ruxolitinib in combination with blinatumomab and inotuzumab in relapsed Ph-like ALL. Case report. Tertiary referral hospital. Ph-like ALL patient harboring a CRLF2 mutation. Our patient received three cycles of first-line Hyper-CVAD: 1A/1B and 2A. BMBx after the third cycle revealed persistent disease. He then received two cycles of second-line ruxolitinib/blinatumomab prior to disease progression. He was then treated with three cycles of third-line ruxolitinib/inotuzumab followed by allogeneic transplant. Reports encouraging the use of JAK inhibitors in CRLF2 Ph-like ALL exist for children, and trials are currently ongoing for adolescents and young adults [NCT03571321]. Ruxolitinib was used at a starting dose of 15 mg BID, as determined by initial dose escalation phase trials testing the safety of ruxolitinib in myelofibrosis. Dose titration (maximum 25 mg BID/100 mg QD) was implemented according to response and platelet and neutrophil counts. Complete response (CR) and measurable residual disease (MRD). After progressing on Hyper-CVAD, our patient switched to ruxolitinib/blinatumomab and achieved CR with negative MRD after only one cycle of treatment. He progressed on this regimen after cycle 2 and moved to third-line ruxolitinib/inotuzumab. After three cycles, he achieved CR and negative MRD and underwent allogeneic transplant from a matched unrelated donor. Today, our patient is 10 months post transplant and remains in clinical and molecular remission. The combination of ruxolitinib plus blinatumomab or inotuzumab is a promising chemotherapy-free salvage regimen given outpatient for relapsed Ph-like ALL. It achieved CR in our patient prior to allo SCT with a limited side effect profile. Further clinical trials adding ruxolitinib to front-line and next-line therapies are needed.

AML-122 Midostaurin Maintenance versus Allo SCT versus W&amp;W in FLT3-Mutated AML: A “Real-Life” Multicenter Study

FLT3-ITD mutation is associated with adverse prognosis (ELN2017, Dohner et al., Blood 2017) and SCT has been the standard of treatment for FLT3-mutated AML for decades. Midostaurin (Midos) has been approved in combination with intensive chemotherapy (IC) for FLT3-mutated AML; Midos maintenance was part of the treatment schedule in the RATIFY trial but not randomly explored (Stone et al., N Engl J Med 2017). The aims of this study are to analyze the safety and effectiveness of Midos maintenance in FLT3 AML in a real-world setting and evaluate maintenance versus allogeneic stem cell transplantation (alloSCT) versus watch and wait (W&W) and the impact of risk factors. We carried out a retrospective multicenter study (MDA-AML-2018-06) in 27 Spanish centers. age >18 years, FLT3-mutated AML diagnosis according to WHO criteria, and start of treatment with Midos in combination with IC between June 2016 and December 2020. We evaluated the response according to 2017 ELN criteria, toxicity according to CTCAE v4.0, and overall survival (OS) by Kaplan-Meier. Statistical analysis was performed using SPSS version 20.0. A total of 175 (93 female) patients with a median age of 53 years (18-76 years) were included. The median OS for the whole population was not reached; 24-month OS was 68%. Of those who achieved CR after Induction 1 or 2 (144 patients, 81.4%), 24 received maintenance, 76 were consolidated with alloSCT, and 41 proceeded to W&W. The only AE during maintenance was one case of QT prolongation, which required Midos discontinuation. There were no cases of febrile neutropenia nor deaths related to Midos. Regarding OS, the ELN2017 classification resulted in a trend of differences in all groups: maintenance, alloSCT, and W&W. We observed significant differences for maintenance versus W&W (P=0.001) in low- and intermediate-risk patients. Comparing maintenance and alloSCT, we observe no differences in the Int ELN2017 group. Our experience confirms the safety of maintenance therapy in AML FLT3 patients after IC. We also observed a benefit for maintenance versus W&W in the low- and intermediate-risk population.

Impact of second primary malignancy post-autologous hematopoietic stem cell transplantation on outcomes of multiple myeloma: A CIBMTR analysis.

8057 Background: Following autologous hematopoietic stem cell transplant (auto HCT), maintenance therapies improve survival, reduce relapse risk in multiple myeloma (MM), and are the de facto standard-of-care. However, clinical trials have shown an increased risk of second primary malignancies (SPM) with maintenance therapy, including second hematological malignancies (SHM). We examined data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to evaluate the impact of SPM on progression-free (PFS) and overall survival (OS) and the utilization of allogeneic HCT in patients with therapy-related myeloid neoplasms (t-MN). Methods: Adult patients (pts) with MM who underwent first auto HCT in the United States with a melphalan conditioning regimen from 2011-2018 and subsequently received maintenance therapy were included (N=3948). The primary endpoint of interest was the impact of SPM and SHM on OS. Multivariate analytic (MVA) modelling was applied, accounting for competing risks while integrating significant covariates to determine the impact of SPM on PFS and OS. Finally, we studied the utilization and survival following allogeneic HCT for SHM. Results: Baseline characteristics were similar between the two groups. Maintenance regimens used were lenalidomide (2836, 72%), bortezomib (370,9 %) or lenalidomide + bortezomib (372, 9%) based combinations. At a median follow up of 37 months, 175 (5%) pts developed SPM, including 112 (64%) solid 36 (21%) myeloid, and 27 (15%) lymphoid cancers. In MVA, the development of SPM and SHM was associated with an inferior PFS (HR 2.62, P&lt;0.001 and HR 5.01, P&lt;0.001, respectively) and OS (HR 3.85, P&lt;0.001 and 8.13, P&lt;0.001, respectively). The two commonest causes of death were MM (42%) and SPM (30%) for those developing SPM. Similarly, MM (53%) and SHM (18%) were the two commonest causes of death for those developing SHM. Nine (14%,5 t-MDS and 4 t-AML) of 63 patients with SHM underwent an allogeneic HCT. Patients undergoing allogeneic HCT were more likely to have Karnofsky score ≥90 (100% vs. 50%, P=0.02) compared to those who did not. One year survival from allo SCT was 66.7% (CI 34.6-92%). Conclusions: The three-year cumulative incidence of SPM was 3.3 (2.6-4)% in this large contemporaneous CIBMTR cohort. Disease relapse remains the primary cause of death in MM patients who develop SPM or SHM. Given the median OS for MM is now &gt; 10 years, longer follow-up is needed to assess the SPM and SHM risks with maintenance therapy post-auto HCT.

Granulocytic sarcoma with unusual localizations (breast and stomach) without bone marrow involvement after the allogeneic transplantation

Granulocytic sarcoma (GS) is a rare extramedullary solid tumor composed of immature myeloid cell that is associated with acute myeloid leukemia or myelodysplastic syndrome. Espe­cially, the involvement of the breast as a pattern of relapse after allogeneic bone marrow transplantation ( allo SCT) is extremely rare. We report the case of a 57-year-old woman who palpated a painless lump in the superior quadrant of her right breast. Her past medical history was a myelodysplastic syndrome ( MDS) treated with bone marrow transplantation. Imaging work-up by mammogram and ultrasonography ( US ) showed solitary mass suspect of malignancy in breast. Tru-cut biopsy was performed from the suspect palpable mass of the right breast. Histologic findings were compatible with a granulocytic sarcoma in breast. While she was also evaluated for mass in the breast, also investigated by endoscopy for the symptoms of gastrointestinal system. The endoscopic biopsy showed diffuse neoplastic infiltration similar the pathology of the breast. GS of the breast is a rare extramedullary involvement of hematologic diseases. There are no the specific radyologic features in the presentation with GS of the breast. Our case also showed that careful histopathological review along with all panel of immunohistochemistry is extremely important for diagnose.

Granulocytic sarcoma with unusual localizations (breast and stomach) without bone marrow involvement after the allogeneic transplantation

Granulocytic sarcoma (GS) is a rare extramedullary solid tumor composed of immature myeloid cell that is associated with acute myeloid leukemia or myelodysplastic syndrome. Especially, the involvement of the breast as a pattern of relapse after allogeneic bone marrow transplantation (allo SCT) is extremely rare. We report the case of a 57-year-old woman who palpated a painless lump in the superior quadrant of her right breast. Her past medical history was a myelodysplastic syndrome (MDS) treated with bone marrow transplantation. Imaging work-up by mammogram and ultrasonography (US) showed solitary mass suspect of malignancy in breast. Trucut biopsy was performed from the suspect palpable mass of the right breast. Histologic findings were compatible with a granulocytic sarcoma in breast. While she was also evaluated for mass in the breast, also investigated by endoscopy for the symptoms of gastrointestinal system. The endoscopic biopsy showed diffuse neoplastic infiltration similar the pathology of the breast. GS of the breast is a rare extramedullary involvement of hematologic diseases. There are no the specific radyologic features in the presentation with GS of the breast. Our case also showed that careful histopathological review along with all panel of immunohistochemistry is extremely important for diagnose. Keywords: myelodysplastic syndrome; granulocytic sarcoma; allogeneic bone marrow transplantation.

Survival of Patients with Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation: An Experience in Developing Country.

Background: Allogeneic stem cell transplantation (allo-SCT) is the highest potential treatment for long-term survival as post-remission therapy for acute myeloid leukemia (AML). The aim of this study was to estimate the overall survival (OS) of patients with AML after allo-SCT and to identify the factors affecting them as a prognostic factor for the survival of patients. Material and Methods: In this retrospective cohort study, data of patients with AML who underwent allo-SCT at Taleghani bone marrow transplantation and cell therapy center in Tehran, Iran, from May 2009 to September 2016 were used. A total of 101 patients were enrolled and death time was considered as a failure event for them. Kaplan-Meier method, log-Rank tests, and Cox proportional hazard model were used to evaluate OS and to identify the risk factors of patient’s survival. The SPSS software version 21 was used for the analysis of data and P<0.05 was considered as a significant level. Results: Of 101 patients with AML, 49 (48.5%) were males. The median age at allo-SCT was 32.76 years and 42 patients (41.6%) died. The 5-year OS and disease-free survival (DFS) was 56% (95%CI: 51-61%) and 52% (95%CI: 57-47%), respectively. Multivariate analysis by Cox regression indicated that OS has a significant relationship with primary WBC count and relapse (P=0.001). Conclusion: Our results showed that allo–SCT has nearly the same outcome in developing countries and the WBC count and relapse are effective factors on the chance of survival in AML patients after allo-SCT.

Granulocytic Sarcoma with unusual localizations (breast and stomach) without Bone Marrow involvement after the Allogeneic Transplantation

Granulocytic sarcoma (GS) is a rare extramedullary solid tumor composed of immature myeloid cell that is associated with acute myeloid leukemia or myelodysplastic syndrome. Espe­cially, the involvement of the breast as a pattern of relapse after allogeneic bone marrow transplantation ( allo SCT) is extremely rare. We report the case of a 57-year-old woman who palpated a painless lump in the superior quadrant of her right breast. Her past medical history was a myelodysplastic syndrome ( MDS) treated with bone marrow transplantation. Imaging work-up by mammogram and ultrasonography ( US ) showed solitary mass suspect of malignancy in breast. Tru-cut biopsy was performed from the suspect palpable mass of the right breast. Histologic findings were compatible with a granulocytic sarcoma in breast. While she was also evaluated for mass in the breast, also investigated by endoscopy for the symptoms of gastrointestinal system. The endoscopic biopsy showed diffuse neoplastic infiltration similar the pathology of the breast. GS of the breast is a rare extramedullary involvement of hematologic diseases. There are no the specific radyologic features in the presentation with GS of the breast. Our case also showed that careful histopathological review along with all panel of immunohistochemistry is extremely important for diagnose.

CPX 351 As First Line Treatment in Higher Risk MDS. a Phase II Trial By the GFM

▪Background and aims: intensive chemotherapy (IC) has been used since the early 90's in the treatment of higher risk MDS, yielding 40 to 50% complete response (CR) but prolonged myelosuppression and 10 to 30% early deaths. IC is also recommended before allogeneic (allo) SCT when marrow blasts are increased (De Witte et al, Blood, 2017). CPX-351, a liposomal combination of cytarabine and daunorubicin, proved greater efficacy than classical IC with 3+7 in secondary-AML, including in patients with 20-30% marrow blasts and those who subsequently received allo SCT (Lancet et al, Lancet Haematol, 2021). We evaluated response to CPX-351 in a group of untreated higher risk MDS patients, most of whom were candidates for allo SCT.Methods: This prospective study, involving 12 GFM centers, included int-2 or high IPSS MDS, previously untreated with HMA or chemotherapy, and aged <70 years. CPX-351 induction treatment was given at 44mg/m 2 (DNR)/ 100mg/m 2 (CYT)/ day on days 1, 3 and 5. A second induction cycle (same daily dose, days 1 and 3 only) was allowed in patients who failed to achieve at least partial response (PR) according to IWG 2006. Consolidation cycles (same daily dose for one day) were planned (4 cycles) in responders. Allo SCT could follow after 1 to 4 consolidation cycles. Response to induction treatment, evaluated per protocol between day 28 and day 42, often had to be delayed due to prolonged cytopenia. For response evaluation, ELN 2017 criteria for AML were used in addition to IWG 2006 criteria for MDS, as the latter often proved difficult to interpret in the presence of persisting moderate cytopenia (especially the requirement of a Hb level ≥ 11 g/dl for CR definition).Results: 31 patients were included between July 2020 and January 2021. Median age was 62 years (range 31-69); WHO classification: 26 MDS-EB2, 5 CMML-2; IPSS: int-2: 84%, high: 16%; R-IPSS: intermediate: 29%, high: 55%, very high: 16%; karyotype: 2 very good, 22 good, 3 intermediate, 2 poor, 2 very poor. 27 patients received one induction cycle and 4 (in stable disease (SD) after the first cycle), a second induction cycle. Response rates, eventually evaluated a median of 53 days (range 28-112) from onset of induction, were with ELN 2017 criteria: CR: 52%, CRi: 13%, MLFS: 23%, SD: 13% and with IWG 2006 criteria : CR: 23%, mCR: 45%, mCR + HI-P: 6%, mCR + HI-P + HI-N: 6%, mCR + HI-N: 3%, PR: 3%, SD: 13%. Minimal residual disease assessment by NGS and flow cytometry will be presented at the meeting. 24/27 patients with baseline marrow blasts >10%, reached <5% blasts after induction treatment (figure 1). Median time to platelets >20G/L and >50G/L were: 16 (range 0-55) days and 28 (range 8-51), respectively and to ANC >1G/L: 26 (range 2-60) days. Only one patient had grade ≥ 3 mucositis and 4 had grade ≥ 2 alopecia during induction treatment. No patient died during induction treatment or required management in the intensive care unit.With a median follow-up of 201 days (range 102-350), 22 of the 30 patients initially considered for allo SCT received transplant after no (10 pts), 1 (9 pts), 2 or 3 (3 pts) consolidation cycles and 5 are planned for allo SCT. Reasons for not being transplanted were, investigators' choice (n=1), relapse (1), no donor (1) and invasive fungal infection (n=1). None of the 4 non transplanted patients received consolidation cycles. Reasons for not receiving consolidation cycles were persistent cytopenia (n=5), cardiac toxicity (n=2), failure to achieve CR or PR (n=2). At the time of analysis (June 2021), 4 patients had relapsed, after 3 to 6 months of response.Conclusions : CPX-351 is effective in higher risk MDS/CMML, especially to achieve blast clearance, and as a bridge to allo SCT.Figure 1: waterfall plot according to IWG 2006 and ELN 2017 criteria [Display omitted] DisclosuresFenaux: Novartis: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria; Takeda: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. OffLabel Disclosure:CPX-351 use off-label for myelodysplastic syndroms in a prospective trial

Outcomes for Myelofibrosis Patients Following Myeloablative Allogeneic Stem Cell Transplantation Using the Orca-T Graft from HLA-Matched Related and Unrelated Donors

Background: Allogeneic stem cell transplantation (allo SCT) is the only potentially curative therapy for patients with intermediate-2 and high-risk myelofibrosis (MF). Allo SCT for MF has historically been challenging as many patients are transplanted with active or advanced disease and immune reconstitution in MF patients is often hindered by inflammation and bone marrow fibrosis. When compared to non-SCT therapies, MF patients who receive allo SCT achieve long-term survival benefits. However, it comes with an upfront cost of an increased risk of non-relapse mortality in the first year after allo SCT (Gowin K et al, Blood Av 2020). Therefore, there is an unmet need to improve on the early outcomes of transplantation for MF.Methods: We reviewed MF patients who underwent myeloablative allo SCT with Orca-T derived from HLA matched donors on NCT01660607 and NCT04013685. Orca-T is an investigational cellular product comprising stem and immune cells that leverages highly purified donor regulatory T cells to control alloreactive immune responses. Single agent GVHD prophylaxis was administered as tacrolimus or sirolimus.Results: We present outcomes for 7 MF patients with DIPSS risk of int-1 (n=1), int-2 or higher risk MF (n=6) treated with the Orca-T graft and compared this to 6 MF patients who underwent standard of care (SOC) allo SCT at Stanford, between 2017 - 2021 (Table 1). All patients were high or very high-risk based on MIPSS70 plus score v, 2.0. All patients had 10/10 HLA-matched donors, except 1 of 7 Orca-T patients who had 9/10 HLA-matched donor. All but 1 patient in both, Orca-T and SOC, recipients had prior Jakafi exposure.All Orca-T recipients had splenomegaly with spleen size of 16.3 - 23 cm. Engraftment occurred at median of D+13 (range 10-29) and 6 of 7 patients had 100% CD3 donor chimerism at D+100. 1 patient was 90% CD3 donor chimerism at D+100 but achieved 100% CD3 donor chimerism at D+180. All patients had significant marrow fibrosis, MF grade 2 or 3, before allo SCT. Regression of marrow fibrosis to MF grade 0 or 1 was noted by D+ 100 in 7 of 7 Orca-T recipients but only in 1 of 6 SOC patients. Orca-T recipients did not have grade 2-4 acute GVHD and 1 of 7 recipients had extensive chronic GVHD. Tacrolimus was tapered off in 3 of 7 patients at D+180. SOC recipients had 2 of 6 recipients with grade 2-4 acute GVHD, 3 of 6 recipients with extensive chronic GVHD and only 1 recipient was taken off tacrolimus at D+180. There were no deaths in Orca-T recipients and 2 deaths in SOC recipients before D+180, cause of death was acute GVHD and relapse. Finally, when compared to standard allo SCT, Orca-T recipients may have a reduced frequency and severity of infections without significant consequences while the SOC patients had severe and often multiple infections.Conclusion: Our data indicates that Orca-T graft was well tolerated and potentially efficacious in MF patients undergoing allo SCT. We observed early regression of marrow fibrosis at D+100 in all Orca-T recipients. This limited data suggests that Orca-T may afford an early resolution of an inflammatory microenvironment that allows for robust immune reconstitution and potentially lower incidence of serious infections. Orca-T is under continued investigation to reduce early non-relapse mortality for MF. [Display omitted] DisclosuresGandhi: CareDx Inc: Honoraria; Gamida Cell: Consultancy, Membership on an entity's Board of Directors or advisory committees. Muffly: Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy; Astellas, Jasper, Adaptive, Baxalta: Research Funding; Adaptive: Honoraria, Other: fees for non-CME/CE services: , Research Funding. Shiraz: Kite Pharma-Gilead: Research Funding. Fernhoff: Orca Bio: Current Employment. McClellan: Orca Bio: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Gotlib: Allakos: Consultancy; Cogent Biosciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Chair for the Eligibility and Central Response Review Committee, Research Funding; PharmaEssentia: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kartos: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Deciphera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Meyer: Triursus Therapeutics: Current holder of stock options in a privately-held company; GigaImmune: Current holder of stock options in a privately-held company; Orca Biosystems: Research Funding; Indee, Jura: Consultancy.

Outcomes of Chronic Lymphocytic Leukemia and Richter Transformation Following Discontinuation of Non-Covalent Bruton's Tyrosine Kinase Inhibitors

Outcomes of Chronic Lymphocytic Leukemia and Richter Transformation Following Discontinuation of Non-Covalent Bruton's Tyrosine Kinase Inhibitors