Citations

207 Background: CAR-T & bispecific antibodies (BsAb) for large B-cell lymphoma offer deep responses, but have unique toxicities requiring close monitoring. Different practice settings have varied strategies for managing these toxicities, leading to increased costs, healthcare resource use, & reduced quality of life. With no direct comparison, rationale for therapy selection may vary. This study explores provider choices, sequencing strategies & access barriers. Methods: A survey of US-based Hematologists was conducted on practice demographics, therapy availability, preferences, & barriers in LBCL. Responses were analyzed across clinical scenarios. Results: Responses were received from 45 physicians. Availability of CAR-T & BsAb varied with 75% prescribing both, & only BsAb being available at 9% of providers’ centers. There was a strong preference for CAR-T over BsAb—higher among academic vs. nonacademic providers (96% vs. 78%; p = 0.03) & at CAR-T vs. non-CAR-T centers (100% vs. 72%; p = 0.001). Even at BsAb-only centers, preference leaned toward CAR-T, though notably lower compared to CAR-T centers. Among centers without either, 86% preferred CAR-T. Practice volume had no impact. Reasons for favoring CAR-T included perceived better outcomes (55%), shorter treatment (26%), center choice (19%), more experience (48%), & curative potential (21%). BsAb selection was driven by CAR-T unavailability & logistical barriers (distance to specialized center, insurance delays, referral complexity, manufacturing time, & hospitalization needs). Axi-cel was preferred by 69% ( p = 0.0001) vs. other CAR-T for third-line or later due to experience with use, response rates, center choice, & logistical ease. Liso-cel (26%) & Tisa-cel (2%) were chosen for perceived favorable toxicity over Axi-cel. Axi-cel was also preferred second-line vs. Liso-cel (73% vs. 24%; p < 0.0001) for similar reasons. Among BsAb, Epcoritamab was favored by 56% for administration ease (subcutaneous), experience, & center preference; Glofitamab by 42% for shorter duration, experience, & center preference. There was no difference by academic vs nonacademic practice & volume for both CAR-T & BsAb. In patients with prior non-CAR-T anti-CD19 therapy, providers chose CD19 CAR-T over CD20 BsAb (80% vs. 18%; p < 0.0001). For relapse after second-line CAR-T, 78% providers preferred BsAb as the next line over other options ( p < 0.0001) due to more favorable response rates, toxicity profile, & experience with use. Providers prioritized response rates, survival, & toxicity profile in their treatment decisions. Logistics, duration, frequency, & cost were less important. There were no differences based on practice setting & CAR-T experience. Conclusions: Despite higher preference for CAR-T due to perceived superior outcomes, access barriers exist. Efforts to streamline referral pathways, logistics, & expand availability are crucial to improve outcomes.

Abstract The treatment patterns and clinical outcomes for patients experiencing progression of disease (POD) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) mantle cell lymphoma (MCL) are undefined. We identified all patients who received CD19-directed CAR T-cell therapy for R/R MCL therapy across 15 international centers, and studied those experiencing POD post–CAR T-cell therapy in detail. We extracted clinical/treatment/pathologic variables, and associated these features with survival outcomes. In total, 384 patients received CAR T-cell therapy, and 135 (35%) experienced POD. POD occurred at a median of 6 months following CAR T-cell therapy infusion, and most (64%) patients with POD had complete response as best response to CAR T-cell therapy. Tumor features at POD included blastoid/pleomorphic morphology in 29 of 78 (37%) patients, and TP53 mutation in 21 of 41 (51%) patients. Following POD, 17 patients received no further therapy, 13 underwent local therapy, and 105 received systemic therapy. The most common first-line systemic therapies were chemo(immuno)therapy (22 patients; overall response rate [ORR], 40%), pirtobrutinib (17 patients; ORR, 36%), and bispecific antibodies (13 patients; ORR, 67%). Among patients experiencing POD, the median progression-free survival and overall survival (OS) were 2.5 months and 5.4 months, respectively, from POD. Lack of response to CAR T-cell therapy and short time from CAR T-cell therapy infusion to POD (&lt;3 vs 3-6 vs &gt;6 months), among other factors, were associated with inferior OS after POD. In conclusion, we confirm the challenging prognosis for patients experiencing POD following CD19 CAR T-cell therapy for R/R MCL, and establish a benchmark for future investigations in this patient population.

ABSTRACT Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19‐directed chimeric antigen receptor T‐cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry. Median age was 64 years (range: 30–86) and median prior lines of therapy was 4 (range: 1–18). Most patients (78%) received axicabtagene ciloleucel, with 67% of patients having resistant disease at the time of CAR T infusion. At a median follow‐up of 25 months (range: 1–72) from CAR T infusion, the 2‐year overall survival (OS) was 57% (95% CI: 53–60) and progression‐free survival (PFS) was 43% (95% CI: 40–47). The 2‐year cumulative incidences of relapse or progression (rel/prog) and non‐relapse mortality (NRM) were 47% (95% CI: 44–51) and 9% (95% CI: 7–11), respectively. The overall response rate to CAR T was 76%, with a complete response rate of 63%. Grade ≥ 3 cytokine release syndrome (CRS) was observed in 7.1% and grade ≥ 3 immune effector cell–associated neurologic syndrome (ICANS) in 21.6% of patients. Multivariable analysis suggested that resistant disease status at the time of CAR T, use of bridging therapy, and high comorbidity index ≥ 3 were associated with inferior PFS and OS. Older age ≥ 60 significantly increased the risk of NRM. Our study suggests that CD19 CAR T is effective and safe for tFL.

Abstract Allogeneic stem cell transplant (ASCT) remains the only curative option in chronic myelomonocytic leukemia (CMML). We retrospectively analyzed 138 CMML patients who underwent ASCT at the Mayo Clinic. Patients who transitioned to ASCT while in chronic phase (Group A) displayed superior post-transplant survival (PTS), compared to those in whom ASCT was performed after blast transformation (BT; Group B) (median 95 vs. 16 months; p=0.01). In Group A, PTS was superior in patients with <5% bone marrow (BM) blasts at time of ASCT (median 164 vs. 13.5 months; p=0.01). Other predictors of superior PTS included day-100 BM blast <5% or normal cytogenetics (median 164 vs 18 months; p=0.01) or presence of chronic graft-versus-host-disease (GVHD; median 164 vs. 26 months; p=0.01). Pre-ASCT hypomethylating agent exposure (HR=2.03; p=0.03), and receiving more than one line of pre-ASCT chemotherapy (p=0.01) predicted inferior PTS. In multivariable analysis, predictors of superior GVHD-free and relapse-free survival (GRFS) included the use myeloablative conditioning and the absence of morphologically or cytogenetically apparent disease at day-100. The use of post-transplant cyclophosphamide (PTCy) was associated with higher cumulative incidence of relapse (p=0.02) and numerically inferior PTS (p=0.1). Group B patients also appeared to benefit from achieving BM blast <5% at time of ASCT (p=0.4) as well as at day-100 (p=0.01), in terms of PTS, while full chimerism and normal cytogenetics at day-100 were associated with superior GRFS. These observations support the value of ASCT in CMML, especially if performed prior to BT and in the presence of <5% BM blasts at time of ASCT. Additionally, the observed detrimental impact of PTCy requires additional studies to confirm and investigate the underlying mechanisms.

9029 Background: Addressing guideline concordant FP and TPP with cancer is challenging, especially for OT. SIM, a well-known education tool, has not been traditionally used to teach these topics. As part of the hematology/oncology fellowship curriculum, we designed a SIM applying LSP to bridge this educational gap. Methods: Applying LSP of contrasting cases, elaboration, feedback, generation and just-in-time telling, chief OTs and faculty designed a SIM with 3 clinical scenarios (CS) and 3 standardized pts (SP): FP for a female pt hospitalized for acute lymphoblastic leukemia tx, FP for a male pt in clinic for germ cell tumor tx, and breast cancer tx for a pregnant pt in 2 nd trimester. OT received written educational materials (WEM) and attended a lecture 1 week and 1 day pre SIM, respectively. OT were split into 2 groups; 1 started in the FP CS and 1 in the TPP CS, and then they switched. To reduce cognitive overload, each OT participated in 1 of 2 FP CS: half in the female FP CS and half in the male. Faculty and chiefs led debriefing sessions after all CS. The FP debrief ended with a special “learner as a teacher” part, where OT who attended the female CS taught those from the male CS about their topic and vice versa. The SIM concluded with "take-home" points. Pre (after having WEM) and post SIM anonymous surveys and verbal feedback assessed OT comfort, perceptions, and knowledge. Results: A 3 hour SIM with 14 OT and 5 faculty was completed successfully. SIM ended with all OT verbally sharing a learning point and positive feedback. All OT filled pre and post SIM surveys. Pre SIM, 17% reported having prior FP education, and 42% had prior TPP education. However, only 8% and 25% felt adequately prepared for FP and TPP discussions, respectively. Post SIM survey showed major improvement in comfort and knowledge about FP and TPP (see table 1). 75% of OT favored a combination of SIM and learning by teaching over other SIM formats. 83% supported having a TPP lecture before SIM. 100% reported satisfaction with FP and TPP SIM’s quality and wanted similar activities in the future. 92% were satisfied with the learner as a teacher tool. 100% felt education about FP and TPP with cancer should be part of fellowship training. Moral/cultural concerns were discussed as possible challenges in FP education. Conclusions: The application of LSP through SIM significantly increased OTs’ comfort discussing FP and TPP with cancer, and objectively enhanced their knowledge on these topics compared to after reading WEM. The SIM was largely perceived as a successful activity to educate about challenging topics and should become part of fellowship curriculum. Pre SIM % Post SIM % Comfortable addressing FP 17 92 Comfortable addressing TPP 8 100 Correct answers about female FP 63 83 Correct answers about male FP 67 94 Correct answers about TPP with cancer 68 98

Abstract Allogeneic hematopoietic stem cell transplant (alloHCT) is considered for all patients with myeloid neoplasms (MNs) harboring TP53 mutations (TP53mut). The aim of this international study across 7 transplant centers in the United States and Australia was to identify factors associated with improved post-alloHCT survival. Of 134 TP53mut MN cases who underwent alloHCT, 80% harbored complex karyotype; 94% of TP53 variants were localized to the DNA-binding domain (DBD). Most common comutations were ASXL1 (7%), TET2 (7%), and DNMT3A (6%). Median post-HCT survival was 1.03 years, and overall survival (OS) at 1 year, 2 years, and 3 years was 51.4%, 35.1%, and 25.1%, respectively. A total of 103 cases (76.9%) met the International Consensus Classification (ICC) criteria for MN with mutated TP53 (referred to as ICC-defined TP53mut MN hereafter). The 3-year OS of ICC-defined TP53mut was significantly shorter compared with that of other TP53mut MNs (3-year OS, 16.9% vs 54.9%; P = .002). ICC-defined TP53mut MNs was independently associated with inferior OS (hazard ratio [HR], 2.62; P = .019). The presence of non-DBD TP53mut only (HR, 3.40; P = .005), DNMT3A comutation (HR, 2.64; P = .016), and pre-alloHCT bone marrow blasts ≥5% (HR, 2.76; P = .006) was independently associated with inferior relapse-free survival (RFS), whereas melphalan-based conditioning was associated with superior RFS (HR, 0.52; P = .005). Combining these variables, we constructed a hierarchical model that stratified patients into low-, intermediate-, and high-risk categories with 1-year RFS of 81.3%, 31.3%, and 6.7%, respectively (P &lt; .001). In conclusion, a subset of MN harboring TP53mut who have low blasts pre-alloHCT and received melphalan-based conditioning derived long-term benefit from alloHCT.

Introduction Chimeric antigen receptor T-cell therapy (CART) has revolutionized the treatment algorithm of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). However, approximately only 40% of cases achieve long-term durable remissions. Prognostication remains important as it would allow more precise prediction of outcomes and develop a personalized treatment approach. Currently, it is unclear whether prognostic factors that have been predictive of outcomes in the pre-CART era, remain important in the current era. We conducted a single center observational study to assess the prognostic significance of extra nodal involvement (ENI) on long-term outcomes following CART in B-cell NHL. Methods The primary aim was to evaluate the prognostic significance of ENI on long-term outcomes in patients with B-cell NHL treated with CART. The second aim was to specifically evaluate the impact of gastrointestinal (GI) involvement. Continuous variables were summarized as median (range) and categorical variables were reported as frequency (percentage). Kaplan-Meier method was used to estimate freedom from events at different time points and draw corresponding survival curves. Log-rank test was used to compare freedom from events between histology groups. Results 74 patients were included in this analysis, with a median age of 62 (18-85) years. Fifty-three (72%) had evidence of ENI. Twenty-four (47%) had GI involvement as the sole site of ENI or with other sites of ENI. Forty-three (58%) patients were male and diffuse large B-cell lymphoma (DLBCL) was the most common histology (n=50 [54%]) followed by transformed follicular lymphoma (n=20 [27%]). Most patients had advanced stage disease at time of CART (n=71 [96%]) and 3 (4%) had CNS involvement at any time prior to CART. Median number of prior lines of systemic treatment were 2 (1-7) and 64 (87%) had progressive disease at time of CART. Axicabtagene ciloleucel was the most used CART product (n=68 [92%]); Grade 3-4 cytokine release syndrome was reported in 6 (8%) patients and grade 3-4 immune effector cell associated neurotoxicity syndrome was reported in 13 (18%) patients. ICU level of care was needed in 22 (30%) patients and 2 patients (3%) developed hemophagocytic lymphohistiocytosis-like syndrome. Sixty patients (87%) achieved an objective response and 34(49%) achieved a complete response. The 1-year OS was 66% (53-81) in patients who had ENI vs. 72% (54-97) in those without ENI (p=0.82); 1-year relapse rates were at 39% (20-54) vs. 36% (10-54) (p=0.95) for patients with ENI vs. those without ENI. No difference was noted between the two groups regarding progression-free survival and non-relapse mortality (NRM). No difference in outcomes was observed when patients who had GI involvement as the only site of ENI or in combination with other sites of ENI were compared to those who did not have GI involvement as one of the sites of ENI. Elevated LDH at the time of CART (HR 2.27 [95% CI 1.05-4.94], p=0.03), development of any grade ICANS (HR 2.77 [95% CI 1.27-6.04], p=0.01) and requirement for ICU level of care (HR 3.25 [95% CI 1.54-6.86], p=0.002) adversely affected OS; the impact of elevated LDH on OS remained significant in multivariate models (HR 2.34 [95% CI 1.05-5.27], p=0.04). Development of any grade CRS was associated with a decreased risk of relapse (HR 0.25 [95% CI 0.11-0.56], p=&lt;0.001) and the requirement of ICU stay adversely affected NRM (HR 2.27 [95% CI 1.05-4.94], p=0.032). Conclusion These results suggest that ENI does not appear to be predictive of long-term outcomes in the setting of CART therapy. Patients who had ENI appeared to derive equal benefit from CART therapy. GI involvement as a site of ENI has been known to be associated with worse survival when compared to other sites of ENI but we did not observe any difference in this subgroup also. Evolving predictive models and/or biomarkers that take in account the dynamics of the interaction between the malignant and CART cells might help better inform prognostication in the current era.