Received Growth Factor Research Articles

Abstract PS08-04: Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC)

Abstract PS08-04: Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC)

Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience

AbstractBendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose of bendamustine with/without rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details, and grade 3 to 5 adverse events (AEs) were analyzed and correlated. In total, 323 patients were enrolled from 9 National Health Service hospitals. Most patients (96%) received bendamustine-R, and 46%, R maintenance. Overall, 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%) and the relative risk highest during maintenance (54%), induction (34%), and follow-up (28%). Toxicity led to permanent treatment discontinuation for 13% of patients, and 2.8% died of bendamustine-related infections (n = 5), myelodysplastic syndrome (n = 3), and cardiac disease (n = 1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor preinduction performance status (PS), poor premaintenance PS, and abnormal preinduction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3 of 10 opportunistic infections occurred despite prophylaxis. In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to those of trial populations of younger, fitter patients. Poor PS, mantle cell histology, and maintenance R were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death, warranting extended antimicrobial prophylaxis and infectious surveillance, especially for maintenance-treated patients.

Second Vs Third Line Treatment with Axicabtagene Ciloleucel for Large B Cell Lymphoma - a Real-Life National Multicenter Retrospective Cohort Study with Propensity Score Matching

Background: Superiority of Axicabtagene Ciloleucel (Axi-Cel) in relapsed/refractory (R/R) large B cell lymphomas (LBCL) compared with standard of care was shown in both the 3 rd and 2 nd line setting. However, optimal timing for incorporation of CAR-T is not well established. We aimed to compare efficacy, toxicity profile, and product kinetics of Axi-Cel as 2 nd vs 3 rd line of treatment. Methods: we performed a national real world retrospective study of consecutive patients treated with Axi-Cel as 2 nd line with propensity score-matched patients treated with 3 rd line treatment. Patients were matched for age (±2 years), Eastern Cooperative Oncology Group (ECOG) performance status, and disease status at lymphodepletion. Disease status and response were defined by the Lugano criteria, cytokine release syndrome (CRS) and immune effector cells-associated neurotoxicity syndrome (ICANS) were defined by ASTCT Consensus (2019) and progression-free survival (PFS) was calculated from infusion to index event. Immunophenotyping from peripheral blood at day 7+ was used to analyze expansion of CAR-T cells. Results: Between 01/2019and 06/2023, 44 patients treated with Axi-Cel fulfilled the inclusion criteria, 22 in each cohort. Groups were well matched in the propensity score domains (mean difference 2, p=.65 for age, mean square .32, p=.57 for ECOG, and mean square .26, p=.61 for disease status at lymphodepletion). Median follow up was 2.2 (range, 1-28.8) months in 2 nd line group and 10.8 (range, 1-39) months in the 3 rd group. Median age was 68 (range, 39 - 84) and 66 (range, 32 - 80) years in the 2 nd and 3 rd line groups, respectively. There were no differences between gender (p=.76), LBCL subtypes (p=.16), % of patients receiving bridging therapy (p=.55), % of patients with elevated LDH levels prior to lymphodepletion (p=.98), and n days from collection to treatment (p=.29) between the 2 groups. There was a lower % of patients with primary refractory disease in the 2 nd, compared to 3 rd line therapy group (63% vs. 36%, respectively, p=.09) and a higher % of patients with transformed disease (42% vs. 14%, respectively, p=.04). Both overall and grade 3-4 incidences of CRS were similar between the 2 nd line and the 3 rd line groups (86% vs. 95%, p=.16 and 18% in both groups, p=1, respectively). Median days to CRS onset was also similar (1, range 0 - 5 and 2, range 0 - 7, p=.1, respectively). Both overall and grade 3-4 incidences of ICANS) were similar between the 2 nd line and the 3 rd line groups (41% vs. 64%, p=.48 and 14% vs. 18%, p=.73, respectively. Median days to ICANS onset was lower in the 2 nd line compared to the 3 rd line group (4, range 0 - 8 and 6, range 0 - 7, p=.06, respectively). There were no differences between the groups in the median tocilizumab doses (p=.21), % of patients receiving steroids (p=.12), cumulative steroids dose (p=.17), % of patients receiving growth factors (p=1), and duration of admission (p=.51). Median day +7 CAR-T blood levels were higher in the 2 nd line compared to the 3 rd line group (126 (range,1-791) vs. 18.1 (range, 0-988) cells/microL, p=.05, respectively). 1-month overall response rate (ORR) was 86% (CR=77%) in the 2nd line group vs 64% (CR=45%), in the 3rd line group, p=.081 Figure 1a. Three-months progression-free survival was 88% (95%, CI 64%-100%) vs. 59% (45%-73%), respectively, Figure 1b. Cox regression identified 2 nd line treatment associated with better progression-free survival (HR=.15, p=.007) and progressive disease at lymphodepletion associated with worse progression-free (HR=8.5, p=.007), while age, gender, and ECOG performance status did not impact progression. Conclusions: This matched comparison showed favorable ORR and PFS rates when Axi-Cel is utilized as a 2nd line treatment vs 3rd line. Toxicity profile is similar. Higher CAR-T expansion in the 2nd line might provide insight regarding product quality and exhaustion phenotype when manufactured earlier in the LBCL treatment course. A longer follow-up is needed to test whether these findings translate to durable remission and cure.

Abstract P4-07-56: Mayo Clinic Enterprise patterns of growth-factor utilization for sacituzumab govitecan (SG)-induced neutropenia among patients with metastatic triple negative breast cancer

Abstract Background: SG was approved in 2020 for the treatment of metastatic triple negative breast cancer (TNBC). The most common grade 3/4 adverse event in the ASCENT trial was neutropenia (51.2%) with a 6% incidence of febrile neutropenia. 1 Package insert recommendations do not endorse primary prophylactic growth factor support, rather only initiating if severe neutropenia occurs on treatment.2 Objective: This study retrospectively reviewed the utilization of growth factor support in patients (pts) with metastatic TNBC initiated on SG at each Mayo Clinic Enterprise site. Methods: We performed a multi-center, retrospective review of all pts with TNBC who received SG from January 2021 to December 2021 at Mayo Clinic sites in Minnesota, Florida, Arizona, and its community-based health system network. Data collected included history of neutropenia with previous cycles of SG resulting in a treatment delay, number of cycles, grade of neutropenia and cycle/day of treatment plan when growth factor added. Pts who received only one dose of SG were excluded. The Fisher’s exact test was utilized to compare the difference in the use of primary prophylaxis between sites. Results: 67 pts received at least two doses of SG. Within this cohort, 42 pts (63%) received growth factor support during treatment with SG. Growth factor support was most often added during the first two cycles (59.5%). A total of 12 patients initiated growth factor with no history of delays related to neutropenia and without neutropenia at the time of administration. Eleven of these pts had growth factor support added on Cycle 1 as primary prophylaxis. Primary prophylaxis was most common at Mayo Clinic – Rochester compared to the other sites (Table 1), however there was not a statistically significant difference (p=0.27). There were 26 pts (39%) with a treatment delay due to neutropenia while receiving SG, of which 21 (81%) were managed with the addition of growth factor (13 pegfilgrastim, 8 filgrastim). The median number of cycles for all pts was 5 (range: 1-25). Pts who received growth factor were treated with a median of 5 cycles (range: 1-25) and pts who did not receive growth factor were treated with a median of 4 cycles (range: 1-19) (p=0.10). Conclusions: We observed wide variability in the use of prophylactic growth factor between Mayo Clinic sites with SG. The optimal practice of growth factor use with SG warrants further exploration.

Adjuvant modified FOLFIRINOX (mFFX) for resected pancreatic cancer (PDAC): Real world outcomes (RWO).

685 Background: Adjuvant mFFX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) is a standard-of-care for fit patients (pts) with resected PDAC, owing to the immediate practice-changing PRODIGE 24/CCTG PA6 trial (2018). Five-year follow-up: median overall survival (mOS) 53.3 months (m) and median disease-free survival (mDFS) 21.4 m for mFFX vs 35.5 m and 12.8 m for gemcitabine (Conroy, JAMA Onc, 2022). RWO for pts outside a clinical trial are lacking. Herein, we report RWO for pts with resected PDAC and intent for adjuvant mFFX at Memorial Sloan Kettering (MSK). Methods: Institutional databases were queried to identify pts with resected PDAC who received any dose of adjuvant mFFX. Demographic, clinicopathologic, genomic, dosing details, and survival data were abstracted from medical and pharmacy records. Primary endpoint was to determine recurrence-free survival (RFS) calculated from start date mFFX to disease recurrence or death and OS calculated from start date mFFX to death. Secondary endpoints included dose reductions, significant treatment delay, toxicity profile, patterns of failure, genomic associations with outcome. RFS and OS are estimated using the Kaplan-Meier method. Study approved by MSK IRB. Results: N = 114 pts with resected PDAC treated with mFFX (> 1 dose) identified between 01/2015- 01/2022. Median age: 67 years (range 35 to 82); N = 43 (38%) > 70 years, N = 18 (16%) > 75 years, N = 2 (2%) > 80 years. Baseline Performance Status recorded in N = 104: N = 31 (30%) ECOG 0, N = 64 (62%) ECOG 1, N = 9 (9%) ECOG 2. Disease stage: N = 36 (32%) stage III, N = 61 (54%) stage II, and N = 17 (15%) pts stage I. Resection status: N = 91 (80%) R0, N = 23 (20%) R1. Presence of lymphovascular invasion: N = 92 (81%), perineural invasion N = 106 (93%). Median baseline CA 19-9: 20 U/mL (IQR; 9, 38). Median follow up: 22.4 m (range 6.2, 50.4). Median time from surgery to start mFFX: 7.4 weeks (IQR; 6.1, 9.3). Median # of mFFX doses received: 12 (IQR; 12, 12), N = 90 (79%) pts completed 12 doses. Dosing details available N = 112. N = 55 (49%) prescribed less than full dose of > one drug at baseline. Dose reductions: N = 57 (51%). N = 69 (62%) received < 12 doses oxaliplatin. N = 97 (87%) received growth factor support. mRFS: 31 m (95% CI; 23, Not Reached). N = 18 (16%) were hospitalized for treatment related adverse events, no therapy related mortality. N = 24 (21%) received adjuvant radiation therapy. One-year OS rate: 93% (95% CI; 89%, 98%) and 2-year OS rate: 78% (95%CI: 70%, 88%). Among patients with recurrence (N = 44), most common sites of first recurrence were: liver (N = 18, 41%), local (N = 14, 32%), and lung (N = 9, 20%). Conclusions: These data endorse mFFX as standard therapy for resected PDAC. The survival signals are encouraging in a prognostically unfavorable albeit select patient population (relative to PRODIGE 24). Dose adjustments to facilitate optimizing tolerability is key. Additional genomic and subtype analyses are underway.

Proteomic Profiles of Cytokine Release Syndromes Following Lisocabtagene Maraleucel and Idecabtagene Vicleucel

Introduction: Adoptive cell therapy with chimeric antigen receptor (CAR) T-cells has improved responses in refractory diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Most CAR-T recipients experience cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) - similar yet clinically distinct inflammatory syndromes related to T-cell activation and expansion of multiple cytokines. Differences in tumor biology between MM and DLBCL and how they contribute to differences in cytokine expression is not well understood. Given different CAR T-cell constructs have varying levels of activation and toxicity, cytokine profiles between products and between different disease entities may inform management. In this study, we used multiplex proteomic profiling to evaluate differences in plasma cytokine signatures between two CAR T-cell products and diseases. Methods: Between September 2021 and March 2022, 20 patients received CAR T-cell therapy and consented to the Yale School of Medicine hematologic disease tissue bank (HIC#1401013259). Two longitudinal cohorts were prospectively enrolled: (1) patients who received lisocabtagene maraleucel (liso-cel) for DLBCL refractory after two lines of therapy, and (2) those who received idecabtagene vicleucel (ide-cel) for MM refractory after 4 lines of therapy. For each patient, the first sample was collected prior to lymphodepleting chemotherapy on day -5 with subsequent samples collected on days 0 (prior to CAR T-cell infusion) and 1, 2, 3, and 7 (after CAR T-cell infusion). Plasma samples were processed and frozen within 1 hour of collection. Proteomic profiling was performed at Eve Technologies (Calgary, Alberta, Canada). The Human 71-Plex Discovery Assay measuring 71 total cytokines and chemokines was used to interrogate each sample time point. Statistical analysis was performed in GraphPad Prism (GraphPad Software, San Diego, CA) and R (R Core Team). Levels of individual proteins were compared using Wilcoxon tests. P-values <0.05 were considered statistically significant. Results: Among 13 patients who received liso-cel for DLBCL (including 2 with transformed follicular lymphoma and 3 with double/triple hit pathology), the median age was 66 years (44-82), 7 (54%) were males, 8 (62%) had KPS ≥ 90, 8 (62%) had bulky disease, median lines of therapy were 4 (2-10), and 11 (85%) received systemic bridging therapy. Seven patients (54%) had any grade CRS, with one patient having grade 3 CRS; 2 (15%) had grade 1 and 2 ICANS. Four patients (31%) received an IL-6 inhibitor. At 3 months of follow-up, the objective response rate was 77% (10/13), of whom two patients had a complete response and 60% (6/10) had any grade CRS. Among 7 patients who received ide-cel for MM, with R-ISS score of 1, 2, and 3 in 4 (57%), 1 (14%), and 2 (29%) patients, respectively, the median age was 61 years (54-79), 5 (71%) were males, 4 (57%) had KPS ≥ 90, 3 (43%) had extramedullary disease, median lines of therapy were 7 (4-13), and 5 patients (71%) received systemic bridging therapy. Six patients (86%) had any grade CRS with no patients having grade ≥ 3 CRS; 3 (43%) had grade 1 ICANS. Four patients (57%) received an IL-6 inhibitor. Five patients (63%) received growth factor support on day 7. At 3 months of follow-up, the objective response rate was 86% (6/7) of whom two patients had a complete response and 83% (5/6) had any grade CRS. In a longitudinal analysis, significantly higher levels of IL-3, IL-5, IL-6, IL-10, IL-15, IL-309, and TNFα were noted during CRS (panel 1). In a comparison between CAR constructs, ide-cel was characterized by significantly higher levels of Eotaxin-2, FLT-3L, IL-5, IL-6, IL-15, I-309, MCP-1, and MCP-4 compared to liso-cel (panel 2). Many of these elevated cytokine proteins are implicated as chemoattractants for other leukocyte subtypes including but not limited to neutrophils, monocytes, eosinophils which may contribute to inflammation and may modulate response, toxicity, or relapse. Conclusions: Ide-cel is associated with a distinct cytokine and chemokine signature compared to liso-cel. This study provides pre-clinical evidence for the role of IL-5 inhibitors to treat or prevent CRS following MM-directed CAR T-cell therapy. Further studies with larger cohorts of patients are needed to validate these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract CT113: A phase II study of prexasertib, a cell cycle checkpoint kinase 1 (CHK1) inhibitor, in platinum-resistant recurrent high-grade serous ovarian cancer (HGSOC) with BRCA wild-type (BRCAwt)

Abstract Background: Platinum-resistance is associated with a poor prognosis in HGSOC and has limited treatment options. Inhibition of CHK1 has shown activity in BRCAwt HGSOC. Here, we report the clinical activity and tolerability of the second generation CHK1 inhibitor, prexasertib, in platinum-resistant BRCAwt HGSOC (NCT02203513). Methods: Eligibility included platinum-resistant recurrent HGSOC women without germline or somatic BRCA mutation, ECOG PS 0-2, good end organ function, and measurable disease. The primary endpoint was response rate (RR). Secondary endpoints were progression-free survival (PFS) and safety. Prexasertib was given at 105 mg/m2 IV every 14 days in a 28-day cycle. CT scans were performed every 2 cycles for RECIST v1.1 evaluation, and safety evaluation using CTCAE v4.0 every cycle. CBC was performed on day 8 of cycle 1 for ANC nadir. Pretreatment clinical samples were collected for biomarker analysis including HR deficiency and circulating tumor cells (CTC). Results: Between January 2017 and November 2020, 49 patients (median age 64.1 years [IQR 56.8 - 69.9]) received at least one dose. 12 (24.5%) patients were primary platinum-resistant, and 37 (75.5%) were secondary platinum-resistant. All were heavily pretreated (median 4 prior systemic therapies [IQR 3 - 7]), including bevacizumab (79%), PARP inhibitors (44%), and both (2%). 39 patients were evaluable by RECIST and RR was 30.7%. The median PFS was 5.8 months (range 1.7-26.4 months). The median duration of response among PRs was 5.5 months (range 1-19.8 months). The clinical benefit rate (PR+CR+SD &amp;gt;4 months) was 84.6%. 10 patients were inevaluable due to: withdrawal of consent (n=2), intercurrent illness related to disease (tumor invasion of mainstem bronchus (n=1) or vaginal wall (n=1), small bowel obstruction (n=2), infection (n=2), failure to thrive (n=1), and pneumothorax secondary to thoracentesis (n=1) during cycle 1. The common (&amp;gt;10%) grade 3 or 4 adverse events (AEs) included neutropenia (85%, 42/49) based on the cycle 1 day 8 CBC at the time of ANC nadir, lymphocytopenia (46%, 23/49), thrombocytopenia (40%, 20/49), anemia (30%, 15/49), and febrile neutropenia (12%, 5/49). 83% (41/49) of patients received growth factors support to avoid subsequent treatment delays. There were no deaths on the study. No significant difference of RECIST response or PFS was observed in patients with high (≥2) vs low (&amp;lt;2) CTC at baseline. Conclusions: Prexasertib monotherapy resulted in clinical benefit in subgroups of heavily pretreated BRCAwt platinum-resistant HGSOC. Prexasertib was well tolerated with manageable grade 3/4 AEs. Further studies on predictive biomarkers are ongoing. Citation Format: Grant Zurcher, Ann McCoy, Brooke Solarz, Jay Nair, Min-Jung Lee, Jane B. Trepel, Christina M. Annunziata, Jung-Min Lee. A phase II study of prexasertib, a cell cycle checkpoint kinase 1 (CHK1) inhibitor, in platinum-resistant recurrent high-grade serous ovarian cancer (HGSOC) with BRCA wild-type (BRCAwt) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT113.

Effectiveness, Safety, and Cost Implications of Outpatient Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma.

Autologous hematopoietic stem cell transplant (aHCT) has become standard care for patients with multiple myeloma (MM). Outpatient aHCT with high-dose melphalan conditioning has reduced costs and length of hospital stay. This study aimed to highlight the effectiveness, safety, and cost implications of outpatient vs inpatient aHCT at a tertiary academic medical center, as well as the utility of growth factor use in these patients. Using an institutional HCT database, a total of 100 patients undergoing aHCT for MM were identified; 50 patients who underwent aHCT in the outpatient setting (chemotherapy and stem cell infusion followed by inpatient admission if needed) were compared with 50 patients in the inpatient setting (chemotherapy and stem cell infusion followed by discharge to outpatient setting). Patients were excluded if the melphalan dose was less than 200 mg/m2. Outcomes assessed through retrospective chart review included time to engraftment, incidence of infection, febrile neutropenia, growth factor use, and total length of inpatient stay through day +100. Time to neutrophil and platelet engraftment was shorter in the outpatient group than in the inpatient group (14 vs 16 days and 19 vs 21 days, respectively; P < 0.001). Median length of hospital stay was also shorter in the outpatient group (8.5 vs 15.5 days, respectively; P < 0.001). Ninety percent of the outpatient group required admission for neutropenic fever, and 60% of these patients received growth factor support starting at a median of 9 days after stem cell infusion, for a median duration of 4 days. Compared to 16 patients who did not receive growth factor support, these patients had a significantly shorter time to neutrophil recovery (13 days with vs 15 days without growth factor, P = 0.02) and no difference in the total length of hospital stay (8 days with vs 10 days without growth factor, P = 0.43). For adult patients with MM undergoing aHCT, the outpatient setting is safe and reduces the total length of hospital stay and thus overall transplant costs. Growth factor support for patients with febrile neutropenia may not reduce length of stay for subsequent hospitalizations.

High Dose Fractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone (mHyperCVAD) Is an Active Regimen in Heavily Pretreated Relapsed/Refractory Multiple Myeloma, Enabling Access to Experimental Therapies

BackgroundTherapeutic advancements and deeper understanding of disease biology have helped improve the outcomes of multiple myeloma (MM). However, there is no consensus regarding the optimal management of patients whose disease becomes refractory to the three main class of drugs [proteasome inhibitors (PI), immunomodulatory drug (IMiD), and monoclonal antibodies (mab)] or among those presenting with complications secondary to rapidly progressive disease. While chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engagers have yielded high rates of durable responses, access to these therapies in clinical trials is often hindered by high disease burden compromising eligibility. We evaluated the use of a combination of cytotoxic agents (cyclophosphamide, doxorubicin, vincristine, and dexamethasone; mHyperCVAD) in this challenging population.MethodsThis is a retrospective, single center study evaluating the safety/tolerability and efficacy of mHyperCVAD in relapsed and refractory MM (RRMM). The regimen consists of cyclophosphamide 300 mg/m2 IV every 12 hours on D1-4 (total 2400 mg/m2), vincristine 0.4 mg/day IV continuous infusion D1-4 (total 1.6 mg), doxorubicin 9 mg/m2/day IV continuous infusion D1-4 hours (total 36 mg/m2) and dexamethasone 40 mg PO daily D1-4. Adult patients with RRMM were included if they received ≥1 cycle of mHyperCVAD between 2019-2021. Patients with primary plasma cell leukemia were excluded. Response was assessed by International Myeloma Working Group Uniform Criteria. Overall response rate (ORR) and disease control rate (DCR) were defined as ≥ partial response and ≥ stable disease, respectively. Patients were censored for progression free survival (PFS) at the last follow-up date if neither progression nor death occurred. All patients received growth factors, and infectious disease prophylaxis per institutional standard. Toxicities were graded using CTCAE v5.0 up to 30 days post therapy.ResultsBetween 1/2019 and 7/2021, 39 patients met the inclusion criteria and received 44 courses of mHyperCVAD (four patients received mHyperCVAD at more than one timepoint). The median age was 54 years (range 32-71), 56% male. 36% patient had ISS stage III disease and 56% had high risk disease [t(4;14), t(14;16), del17p, +1q]. The median lines of therapy prior to mHyperCVAD were 3 (range 1-12) with 93% triple class refractory (refractory to PI, IMID and mab) and 64% penta-refractory (refractory to 2 PI, 2 IMiDs and mab) and 76% had received a prior autologous transplant. The median number of mHyperCVAD cycles per course was 1 (range 1-8). Baseline characteristics are summarized in Table. Eleven courses (25%) were administered as bridge after lymphocyte collection for the manufacture of CAR-T cells and prior to lymphodepletion chemotherapy (100% triple class refractory and 91% penta-refractory) with ORR 18% and DCR 72%. Thirty-three courses (75%) were used as salvage for rapid disease control. The most common toxicities with mHyperCVAD were hematologic (65% grade 3/4 toxicities) with 20% incidence of febrile neutropenia. Four patients died during mHyperCVAD therapy due to rapidly progressive disease and one patient died due to sepsis.For the entire cohort, the ORR is 50% (≥VGPR 30%) with a DCR 82%. Additionally, 39% could proceed with experimental CAR-T cells and/or bispecific T cell engagers. The median progression free survival is 3.6 months, and the median overall survival is 8 months from start of mHyperCVAD with 10.5 months median follow up. The most common cause of death was progressive disease (39%).ConclusionmHyperCVAD is an efficacious cytotoxic chemotherapy regimen which can achieve rapid disease control allowing patients an opportunity to proceed with additional therapies, including investigational agents on clinical trials. It can also be used as an effective bridging strategy among heavily treated, triple class and penta-refractory MM awaiting manufacturing of CAR-T cells with manageable and expected toxicities. [Display omitted] DisclosuresGiri: PackHealth: Research Funding; CareVive: Honoraria, Research Funding. Costa: Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau.

Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.

Hyperfractionated Cyclophosphamide-Dexamethasone (HyperCy-Dex) with or without Carfilzomib (Car) in Patients (pts) with Multiple Myeloma (MM)

Hyperfractionated Cyclophosphamide-Dexamethasone (HyperCy-Dex) with or without Carfilzomib (Car) in Patients (pts) with Multiple Myeloma (MM)

Efficacy, Safety and Cost Implications of Outpatient Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma: A Single Center Experience

Introduction: Autologous hematopoietic stem cell transplant (aHCT) has become a standard of care for patients with multiple myeloma (MM). Outpatient aHCT with high dose melphalan conditioning has been shown to reduce costs and length of hospital stay. This study highlights the efficacy, safety and cost implications of outpatient versus (vs) inpatient aHCT with the initiation of an outpatient aHCT program at a tertiary academic medical center, as well as the utility of growth factor use in these patients. Methods: Using the institutional HCT database, a total of 100 patients undergoing aHCT for MM were identified to compare 50 patients that underwent aHCT in the outpatient setting since May 2018 to 50 patients that underwent aHCT in the inpatient setting prior to May 2018. Patients in the inpatient group were admitted on day -2 with a planned discharge on day +1 for an anticipated length of stay of 4 days, whereas patients in the outpatient group received chemotherapy and stem cells in the outpatient setting. Patients were then hospitalized as needed for febrile neutropenia or other complications requiring supportive care. Patients were excluded if the melphalan dose was less than 200 mg/m2. Data collection was conducted via retrospective chart review. Outcomes assessed included time to absolute neutrophil count (ANC) and platelet engraftment, incidence of infection and febrile neutropenia, growth factor use, and total length of inpatient stay through day +100. Results: Time to neutrophil and platelet engraftment was shorter for the outpatient group as compared to the inpatient group (14 vs 16 days and 19 vs 21 days, P &amp;lt;0.001, respectively). The incidence of infection (~30%) and hospitalization following stem cell infusion (~90%) were similar between the two groups. However, the median length of stay and incidence of more than one hospitalization following transplant were significantly lower in the outpatient group compared to the inpatient group (8.5 vs 15.5 days and 4% vs 26%; P &amp;lt;0.001, respectively). The total number of hospital days were 889 days for the inpatient population and 437 days for the outpatient population for a total reduction of 452 hospital days. The median dose of melphalan was similar between m the two groups (352 mg for the outpatient group vs 348mg for the inpatient group). Based on the institutional costs from August 2020, purchase and administration of melphalan for the outpatient utilization results in an estimated cost savings of $216,000 for every 50 patients. Of the 44/50 (88%) patients in the outpatient group that required hospital admission, 40/44 (90%) had neutropenic fever. A total of 24/40 (60%) of these patients were given growth factor support starting at a median of 9 days (range 4 - 16) after stem cell infusion for a median duration of 4 days (range 1 - 8). When compared to the group of 16 patients that did not receive growth factor, there was a difference in time to neutrophil engraftment (13 days with vs 15 days without growth factor, P = 0.02) There were no significant differences in the time platelet engraftment (20 days with vs 19 days without growth factor, P = 0.20) or length of hospital stay (8 days with vs 10 days without growth factor, P = 0.43). Conclusion: For adult patients with multiple myeloma undergoing aHCT, the outpatient setting is not only safe and effective, but also reduces total length of hospital stay and overall cost of transplant. Growth factor support for patients with febrile neutropenia may not reduce length of hospital stay. Disclosures Neppalli: Sanofi: Membership on an entity's Board of Directors or advisory committees. Edwards:Genzyme: Membership on an entity's Board of Directors or advisory committees.

Reduced-Intensity Induction with Dasatinib Vs. Hypercvad + 2nd Generation TKIs with MRD-Guided Follow-up Therapy Leads to Comparable Rates of MRD-Negative Remission While Reducing Transfusions and Neutropenia in Ph+ ALL

Reduced-Intensity Induction with Dasatinib Vs. Hypercvad + 2nd Generation TKIs with MRD-Guided Follow-up Therapy Leads to Comparable Rates of MRD-Negative Remission While Reducing Transfusions and Neutropenia in Ph+ ALL

Daratumumab (Dara) and hyperfractionated cyclophosphamide (HyperCy)/dexamethasone (Dex) with and without carfilzomib (Car) for the treatment of relapsed/refractory multiple myeloma (RRMM).

e20528 Background: RRMM can be associated with high disease burden and/or end organ damage requiring rapid disease control. Our group has previously published data with hyperCy-bortezomib (bor)-doxorubicin-dex (Tabchi et al. 2019) for such patients (pts). Dara, a monoclonal antibody targeting CD38, has limited overlapping toxicities with cytotoxic chemotherapy, making it an attractive partner for hyperCy-dex. We report our retrospective experience of pts treated with dara-hyperCy-dex ± car. Methods: Between 5/2016-8/2019, 53 pts were treated with dara (16 mg/kg IV d1,8,15,22)-hyperCy (300-350 mg/m2 IV q12h x 6-8 doses d1-3/4)-dex (20-40 mg IV/PO d1-4, 8-11, 15-18, 22-23) alone (27 records), or with car (20 mg/m2 IV d1-2, 27-36 mg/m2 IV d8-9, 15-16) (32 records) on 28 day cycles. Pts received growth factor, anti-fungal, anti-bacterial, anti-viral, and peptic ulcer prophylaxis. High-risk MM (HRMM) was defined by t(4;14), t(14;16), and/or del 17p. Response was assessed by International Myeloma Working Group Uniform Criteria. Overall response rate (ORR) and disease control rate (DCR) were defined as ≥ partial response and ≥ stable disease, respectively. Each instance of treatment (tx) started &gt; 60 days from the previous cycle start date was counted as a separate record. Patient characteristics, progression-free survival (PFS) and overall survival (OS) were assessed per pt, based on earliest administration date. Results: Median age of pts was 61 (26-77) years. Median number of prior therapies was 4 (1-18). Previous exposure to both lenalidomide and pomalidomide (93%), both bor and car (83%), and dara (64%) was frequent. HRMM was present in 20/42 evaluable pts. After a median of 1 cycle (1-5), ORR was 63%, with ≥ very good partial response in 24%. DCR was 86%. Median PFS was 4.3 months. Median OS was 9.7 months. Grade 3-4 hematologic toxicities included 66% neutropenia, 66% anemia, and 68% thrombocytopenia. Grade 3-4 non-hematologic toxicities included 42% febrile neutropenia, 19% bacteremia, and 15% pneumonia. Within 60 days of tx, 7 pts underwent autologous stem cell transplant (ASCT), and 7 pts died. Conclusions: Dara-hyperCy-dex ± car demonstrates a high ORR and DCR in heavily treated and HRMM, allowing bridging of some pts to ASCT. High rates of hematologic toxicity and risk of infection are manageable with twice weekly monitoring for transfusion support, as well as early detection and intervention for infections. Rates of end organ damage reversal will be presented.

Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged &gt; 65 years with advanced pancreatic cancer (APC).

705 Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in APC. However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients &gt; 65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged &gt; 65 years with chemo-naive APC and ECOG PS &lt; 2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using Kaplan-Meier method. Adverse events were recorded on the day of chemotherapy. CA19-9 was measured every cycle and restaging scans were performed every two cycles. Results: Seventy-three patients (median age: 73; range: 66 - 93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months respectively. 66% of patients received growth factor support based on ASCO guidelines and no patients developed neutropenic fever. The incidence of grade &gt; 3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5% respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients respectively. Conclusions: In patients &gt; 65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with historical control from the MPACT study. This regimen allowed for less dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as favorable side effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with APC and poor performance status. Better tolerability may allow for combination with a third agent, such as a targeted or immunotherapy.

Hematologic Toxicities of CAR T-Cell Therapy in Non-Hodgkin Lymphoma

Chimeric Antigen Receptor T-Cell (CART) therapy remains a novel approach for the treatment of relapsed, refractory B-cell Lymphoma. Complications of CAR T-cell therapy including cytopenias, infections, cytokine release syndrome (CRS) and neurotoxicity require aggressive supportive care. The objective of this study was to characterize the incidence of cytopenias and the utilization of growth factor and transfusion support following CAR T-cell therapy. This retrospective, single center study included 38 patients with relapsed, refractory non-Hodgkin lymphoma (NHL), who received CD19 directed CAR T-cell therapy, axicabtagene ciloleucel, as standard of care for the treatment relapsed NHL between January, 2018 and October, 2019. Cytopenias included 34% grade 4 thrombocytopenia (13/38), 76% grade ≥3 anemia (29/38), and 92% grade 4 neutropenia (35/38). Thirty-four percent (13/38) of patients required platelet transfusion support, 76% of patients (29/38) required RBC transfusions, 92% (35/38) of patients became neutropenic and 81.6% (31/38) received growth factor support. Twenty-nine percent of patients were found to have recurrent neutropenia status post recovery of their initial onset. The median initial onset occurred on day +8 (0-+14) and lasted a median of 5 days (0-85 days) with a median ANC nadir of too few cells to count (0-490). The median onset for a 2nd occurrence of neutropenia occurred on day +21 (D+12- D+28) which lasted 1 day (1-11 days) with a nadir of 430 cells/mm³ (0-480). Sixteen percent of patients experienced a 3rd occurrence on day +35 (D+25-+52), lasting a median of 3.5 days (1-19 days) with a median nadir of 335 cells/mm³ (270-440). One patient had a 4th occurrence on day +28 with a nadir of 220 cells/mm³. The etiology of recurrent neutropenia described is unclear. Multiple factors may contribute including bridging therapy, infection, steroids, CRS, and growth factor support. More is data is needed to identify risk factors for recurrent neutropenia.

Safety and Efficacy of Brentuximab Vedotin in Combination with AVD in Stage II-IV HIV-Associated Classical Hodgkin Lymphoma: Results of the Phase 2 Study, AMC 085

Safety and Efficacy of Brentuximab Vedotin in Combination with AVD in Stage II-IV HIV-Associated Classical Hodgkin Lymphoma: Results of the Phase 2 Study, AMC 085

Smart Start: Rituximab, Lenalidomide, and Ibrutinib Alone and in Combination with Standard Chemotherapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Final Phase II Results

Smart Start: Rituximab, Lenalidomide, and Ibrutinib Alone and in Combination with Standard Chemotherapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Final Phase II Results

Hematological Count Recovery in Patients Undergoing Treatment with Chimeric Antigen Receptor T Cells (CAR T)

Hematological Count Recovery in Patients Undergoing Treatment with Chimeric Antigen Receptor T Cells (CAR T)

Abstract P1-17-02: Outcomes and safety of paclitaxel and granulocyte-colony stimulating factor (GCSF) in breast cancer in pregnancy (BCP) - A multi-institutional retrospective analysis

Abstract Background BCP is uncommon; however, the frequency is increasing due to trends in delayed childbearing. Studies have suggested that some systemic therapies, including doxorubicin and cyclophosphamide, can be delivered safely during pregnancy after the first trimester, whereas agents such as trastuzumab and endocrine therapy are contraindicated due to risk to the fetus. Data remain limited on the efficacy and safety of administering taxane chemotherapy or growth factor support during pregnancy. We retrospectively evaluated the safety of systemic therapies, including paclitaxel and GCSF, as well as clinical outcomes, in a multi-institutional cohort of patients (pts) with BCP. Methods Pts treated for BCP from 1996-2018 from 3 large academic institutions were included. Demographic, oncologic treatment, and obstetric/neonatal outcomes data were obtained from medical records. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier; Log-rank test were used to compare different groups/outcomes. Associations were calculated by Fisher's exact test. Results A total of 114 pts diagnosed with BCP were included. The median age was 35 years (range 25-44) and median gestational age at diagnosis was 18 weeks (range 2-38). BCP was predominantly early stage at diagnosis (stage I 28.0%, stage II 53.5%) and ER+/HER2- negative (48.2%). Sixty-three (55.2%) women received chemotherapy, 13 (11.4%) received paclitaxel and 11 (9.6%) GCSF (daily or depot injections) while pregnant. A total of 78% of pts with HER-2-positive BCP (28/36) received trastuzumab after delivery (11% were treated before 2005 and 5.5% were T1a). With median follow-up of 67.7 months, median DFS (stage I-III) was 212.8 months (CI 95% 108.4-317.1), and median OS (stage I-IV) was not reached. Subgroup analysis suggested a higher DFS for pts diagnosed in the 1sttrimester compared to the 3rdtrimester among women with stage II-III (HR 0.25 CI 95% 0.09-0.70, p= 0.03). Among women who received paclitaxel, there was no significant increase in adverse obstetrical/neonatal outcomes: preterm delivery (23.1% vs 13.1%, p 0.39), low weight newborn (7.7% vs 9.1 %, p 1.0), congenital malformations (0% vs 6.1%, p 1.0) or acute neonatal adverse outcomes (7.7% vs 4.0%, p 0.51), which include NICU need and Apgar 5'&amp;lt;7, compared to pts who did not receive paclitaxel. Among pts who received GCSF during pregnancy, adverse outcomes were numerically but not statistically higher than women who did not receive growth factor: preterm delivery (36.3% vs 11.0%, p 0.051), low weight newborn (27.3% vs 6.9%, p 0.058), congenital malformations (9.1% vs 1.0%, p 0.18) or acute neonatal adverse outcomes (18.2% vs 3.0%, p 0.07). Conclusion In this multi-institution cohort of BCP pts, despite a small number of pts, exposure to contemporary therapies including paclitaxel was not associated with unfavorable obstetrical/neonatal outcomes and these results suggest it is safe to administer during pregnancy under the care of a multidisciplinary team. Although not statistically significant, GCSF presented numerical worse outcomes and combining data from several cohorts would be helpful to provide confirmation of these findings. Citation Format: Exman P, Freret TS, Economy KE, Chen WY, Parsons HA, Lin NU, Moy B, Tung NM, Partridge AH, Mayer EL. Outcomes and safety of paclitaxel and granulocyte-colony stimulating factor (GCSF) in breast cancer in pregnancy (BCP) - A multi-institutional retrospective analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-02.