Impact of therapy delays on outcomes in adults with BCR::ABL1 negative b-lineage acute lymphoblastic leukemia (ALL) in the ECOG-ACRIN E1910 trial randomized to conventional chemotherapy +/- blinatumomab

Blood · 2025-11-03

Abstract Background: The addition of the CD19/CD3 bispecific T-cell engager, blinatumomab, to standard consolidation chemotherapy in adults with ALL who achieved a measurable residual disease negative (MRDneg) remission (CR), demonstrated an improvement in 3-year overall survival (OS, 85% vs 68%, HR 0.41, P=0.002) and 3-year relapse-free survival (RFS, 80% vs 64%, HR 0.53) compared to conventional chemotherapy in the ECOG-ACRIN E1910 study (Litzow et al, NEJM 2024). Given the complex therapy in this study, treatment delays and modifications are expected. We herein explored the impact of such delays on patient outcomes. Methods: In the phase 3 ECOG-ACRIN E1910 trial (NCT02003222), adults aged 30-70 years with newly diagnosedALL who had achieved MRDneg CR following induction and intensification were randomized to consolidation chemotherapy with blinatumomab (blina arm) or chemotherapy alone (chemo arm). We examined the association between the timing of the initiation of maintenance therapy and OS and RFS. The expected duration of consolidation was 252 days vs 126 days for patients on the blina and chemo arms, respectively. For this analysis, participants were classified into two groups (no/short delay or long delay) depending on whether they started on time/before or after the median time between the beginning of consolidation and start of maintenance therapy for their treatment group (medians: 335 days, range, 181-457 days vs 176 days, range, 139-265 days for blina and chemo arms, respectively). Multivariate analyses of OS and RFS were performed to examine the effect of no/short delay vs. long delay in starting maintenance. Patients were stratified according to their assigned consolidation treatment arm, and the models were further adjusted for age, sex, white blood cell count, platelets, hemoglobin, peripheral blood blasts, bone marrow blasts, performance status and genetic-genomic risk at diagnosis. Results: Of the 488 patients enrolled, 224 MRDneg patients were randomized to consolidation chemotherapy with or without blinatumomab and 135 of the 224 went on to maintenance therapy on study (N= 66 on blina arm and 69 on chemo arm, respectively). The median follow-up from the time of maintenance registration was 43.4 months. There were no significant differences in baseline characteristics between patients in either arm who experienced no/short delay or long delay. In the blina group, 60 of 66 patients (90.9%) received all 8 cycles of consolidation therapy of which 31 (45.6%) had long delays. Sixty-eight of 69 patients on the chemo arm (98.5%) received all cycles of consolidation therapy, of which 34 (50%) had a long delay. Strikingly, patients who had a long delay before initiation of maintenance had a significant improvement in OS in multivariate analysis compared to patients who had no/short delay (HR 0.31, 95% CI: 0.11-0.91; P =0.03). However, within each treatment group, OS benefit did not reach statistical significance (blina arm: HR 0.04, 95% CI: 0.001-1.64; P =0.09; chemo arm: HR 0.32, 95% CI: 0.08-1.38; P =0.13). Similar results were observed for RFS in multivariate analysis (HR 0.40, 95% CI: 0.16-1.01; P =0.05), though this impact on improved RFS was noted in the chemo arm but not in blinatumomab treated patients (blina arm: HR 0.56, 95% CI: 0.10-3.24; P =0.52; chemo arm: HR 0.19, 95% CI: 0.04-0.83; P=0.03). Additionally, patients who had no/short delay before starting maintenance experienced a longer median duration of maintenance treatment (blina arm, 548 days; chemo arm, 708 days) compared to patients who had a long delay (blina arm 488 days; chemo arm 598 days) before initiation of maintenance (P=0.0008). Conclusion: In the phase 3 randomized ECOG-ACRIN E1910 clinical trial, long delays between initiation of consolidation therapy and start of maintenance therapy were associated with improved OS compared to no/short delays. However, within each treatment group (blina or chemo), no significant difference of OS was observed. We postulate that these longer delays allowed more patients to receive all of the recommended protocol-assigned therapy thereby resulting in improved survival. Furthermore, patients who had no/short delays had a significantly longer duration of maintenance therapy. These data indicate that treatment delays during consolidation do not worsen survival. Further studies are being done to better understand why patients with long delays had better overall survival.

Long-term follow-up of novel post-transplant cyclophosphamide (PTCy) and abatacept (aba) graft-versus-host disease (GVHD) prophylaxis regimen compared to tacrolimus and methotrexate.

Blood · 2025-11-03

Abstract Introduction: Advances in relapse and GVHD prevention have led to improved effectiveness and safety of allogeneic hematopoietic cell transplantation (HCT) over the decades, thus making allogeneic HCT a potentially curative possibility for more patients. Unfortunately, despite improved long-term survival, both relapse and GVHD impact long-term outcomes, and QoL is reduced in HCT recipients (Beer et al., Bone Marrow Transplant, 2025). Given limitations of current treatment and prophylaxis regimens in terms of efficacy, adverse effects, and need for close laboratory monitoring, there is a need for therapies that promote better long-term outcomes after HCT. We report an updated analysis of long-term outcomes and new QoL data on patients who received novel calcineurin inhibitor-free GVHD prophylaxis with PTCy + aba compared to patients who received methotrexate and tacrolimus (Control) in a prospective randomized controlled clinical trial previously described (Koura et al., Blood Advances, 2025: ID IM101-701; protocol #180383). Methods: In this institutional review board approved follow-up, original study participants were contacted 2-5 years post-HCT to complete the validated QoL assessment, Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) (McQuellon, Bone Marrow Transplantation, 1997). Additional long-term outcomes data were obtained from electronic medical record review, including overall survival (OS), relapse, chronic (c)GVHD, cGVHD-relapse free survival (cGRFS), and systemic treatment for cGVHD. Fisher's exact test was utilized for categorical endpoint analyses. FACT-BMT QoL scores were analyzed with the independent two-sample T-test. In this analysis, patients who experienced a catastrophic event, including death or relapse, and those who did not complete the FACT-BMT for other reasons were excluded from QoL analysis. P < 0.05 was considered significant for analyses. Results: 24 patients were randomized to PTCy + aba and 14 to the Control arm and were included in subsequent analyses. Patient characteristics have been previously published. Notably, disease risk was not evenly balanced in the initial trial, with more patients transplanted in complete remission (CR)2 versus CR1 in the PTCy + aba arm [PTCy + aba in CR2 = 8/24 (33%) vs. Control in CR2 = 2/14 (14%)]. At 2-5-year follow-up, there was no difference in cGRFS (p = 0.294) or OS (p = 0.472) between arms. Moderate-severe cGVHD was significantly different, with higher incidence of cGVHD in the Control arm (PTCy + Aba N = 1; Control N = 9; p = 0.0001*). Freedom from relapse was also significantly different, with increased relapse observed in the PTCy + aba arm (PTCy + Aba N = 13; Control N = 2; p = 0.02*). Of the patients who relapsed in the PTCy + aba arm, the majority went on to receive subsequent therapy, including 9 who received donor lymphocyte infusion (DLI) and 1 who received CAR-T therapy. Two patients developed moderate-severe cGVHD following DLI. 6 patients in the PTCy + Aba arm completed a FACT-BMT assessment and had not experienced a catastrophic event at long-term follow-up (M = 91.18, SD = 24.71) versus 8 patients in the Control arm (M = 111.3, SD = 14.11). Between arms, there was no difference between FACT-BMT QoL scores, p = 0.078. Additionally, there was no difference in FACT-BMT scores between arms for those achieving cGRFS (PTCy + Aba N = 5, M = 98.62, SD = 18.66; Control N = 3, M = 118, SD = 17.78; p = 0.20). Non-response rates were greater among patients on the PTCy + aba arm who achieved cGRFS (5/11) versus the control arm (0/3). In the PTCy + aba arm 4 patients required systemic cGVHD therapy > 1-year post-HCT versus 11 in the control arm. Conclusions: This exploratory analysis found the intervention, PTCy + aba GVHD prophylaxis, at 2-5 year long-term follow-up was associated with sustained decreased cGHVD, with no difference in cGRFS and OS compared to the Control arm. There was a trend for more relapses on the PTCy + aba arm. This was confounded by small sample size and the fact that patients were stratified based on GVHD and not relapse risk, resulting in more patients with high-risk disease on the intervention arm.QoL at long-term follow-up was not different between arms, with results also limited by small sample size and confounded by non-response bias. Long-term outcomes, including QoL, are important endpoints to evaluate GVHD prophylaxis regimens and warrant investigation in future prospective studies.

A Multimodal Analysis of Neurotoxicity Following Chimeric Antigen Receptor T-Cell Therapy Using Deep Learning-Based MRI

International Journal of Radiation Oncology*Biology*Physics · 2025-09-01

796 | SERUM AND DEEP‐LEARNING‐BASED MRI BIOMARKERS OF NEUROTOXICITY AND SURVIVAL IMPLICATIONS AFTER CHIMERIC ANTIGEN RECEPTOR T‐CELL THERAPY IN NON‐HODGKIN LYMPHOMA

Hematological Oncology · 2025-06-01

Introduction: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a complication of chimeric antigen receptor T-cell therapy (CAR-T). Quantitative MRI for characterizing ICANS remains underexplored. We present a novel application of deep learning (DL)-based MRI, integrated with clinical and serum biomarkers, to improve characterization of ICANS following CAR-T in patients with non-Hodgkin lymphoma (NHL). Methods: NHL patients who underwent CAR-T at UCSD with a commercial product from 2018 to 2024 were included. ICANS was graded per American Society for Transplantation and Cellular Therapy. Covariables included prior high-dose methotrexate, intrathecal (IT) chemotherapy, central nervous system (CNS) involvement, and prior radiotherapy (RT). Serum markers were collected pre-, 3 days post-infusion, and during ICANS (or 7 days post-infusion for no ICANS). Post-CAR-T MRIs were processed using a 3D U-Net convolutional neural network to quantify T2 FLAIR hyperintensity volumetrics. Logistic regression modeled factors associated with ICANS. Multivariable linear regression modeled factors associated with DL-derived FLAIR. Kaplan-Meier method modeled progression-free (PFS) and overall survival (OS). Results: Of 145 patients, most (63%) had diffuse large B-cell; 10 had follicular or marginal zone lymphoma. 36 had received IT chemotherapy, 20 had prior CNS disease (9 with active CNS disease), 5 had prior CNS-RT, and 35 had prior extracranial RT. Most received axi-cel (73%; 13 tisa-cel, 7 brexu-cel, 19 liso-cel). CRS occurred in 126 patients, and ICANS occurred in 65 patients at a median of 7 days post-infusion (38 gr 1–2, 27 gr 3–4). Prior IT chemotherapy was associated with ICANS (OR 3.3, p = 0.003); CNS disease and prior RT were not associated (Figure A). Higher baseline LDH was associated with ICANS (p = 0.003). Liso-cel was associated with lower odds of ICANS (OR 0.28, p = 0.03). Post-infusion, elevated LDH (p = 0.04) or CRP (p = 0.02) and cytokine release syndrome were associated with ICANS (p = 0.005). Post-CAR-T, 41 patients had ≥ 1 brain MRI (83 MRIs total). Adjusting for age at CAR-T, ICANS severity was associated with greater DL-derived FLAIR volume (gr 3–4 vs. no ICANS, β = 14,047 mm3 p = 0.05; Figure B). PFS did not differ by ICANS (8.1 vs. 13.8 m for ICANS vs. no ICANS; p = 0.23) nor ICANS severity (p = 0.15; Figure C) but did differ by histology (p = 0.02). However, patients with ICANS had worse OS (21.8 m vs. NR for ICANS vs. no ICANS; p = 0.008) and greater ICANS severity was associated with worse OS even when accounting for histology (gr4 = 2.0 m, gr3 = 8.1 m, gr2 = 35.4 m, and NR for gr 1 or no ICANS p = 0.009; Figure D). Conclusions: We demonstrate a novel application of DL-based MRI as a potential biomarker for ICANS post-CAR-T in NHL. These metrics may provide quantitative insight into neurotoxicity and its impact on survival outcomes. These findings warrant further prospective validation to refine the phenotype of patients at risk for ICANS and its prognostic significance. Research funding declaration: None Keywords: non-Hodgkin; other imaging and early detection; immunotherapy Potential sources of conflict of interest: C. Costello Consultant or advisory role: Pfizer, Takeda Honoraria: Janssen, Pfizer, Regeneron, Karyopharm Therapeutics, AstraZeneca, Bristol-Myers Squibb/Celgene Educational grants: Regeneron T. N. Tanaka Consultant or advisory role: CTI BioPharma Corp Honoraria: Gilead Sciences, Survivornet Other remuneration: Function Oncology D. Koura Consultant or advisory role: Bristol-Myers Squibb A. Goodman Consultant or advisory role: Seagen, EUSA Pharma A. Hamdan Other remuneration: Caribou Biosciences, Kite, a Gilead Company M. Y. Choi Honoraria: Janssen Biologics BV B. M. Heyman Consultant or advisory role: AstraZeneca, BeiGene Beijing Educational grants: Genmab/Seagen Other remuneration: Izyme Inc, Century Therapeutics, AstraZeneca, Regeneron E. G. Reid Employment or leadership position: EpicentRx, recipient: An Immediate Family Member Stock ownership: EpicentRx, recipient: An Immediate Family Member D. Tzachanis Consultant or advisory role: Bristol-Myers Squibb

Genomic determinants of treatment outcome and identification of a new genomic subset of adult acute lymphoblastic leukemia from the ECOG-ACRIN E1910 randomized phase III trial

Blood · 2025-11-03 · 1 citations

Abstract Introduction:A comprehensive integration of significantly mutated genes and pathways with molecular subgroups is lacking in adult B-ALL. Furthermore, the genomic drivers underlying each subgroup remain to be identified.We aimed to perform genomic analysis on a large cohort of patients with adult B-ALL, and to correlate genomic markers with achievement of MRD negativity enabling blinatumomab randomization, and with subsequent response to blinatumomab. Methods:For genomic analysis, we studied 569 adults with newly diagnosed B-ALL registered for initial screening on the ECOG-ACRIN-led E1910 trial (NCT02003222), which evaluated the addition of blinatumomab to standard consolidation chemotherapy. The median age was 52 yrs (range 30 to 71 yrs), with 52% males. Analysis was performed on tumor and matched-normal samples using whole transcriptome sequencing (RNA-seq; tumor only; n=569), whole exome sequencing (n=490), whole genome sequencing (n=131), and single nucleotide polymorphism array (n=445). B-ALL cases were classified into 22 molecular groups. Outcome analysis was limited to patients enrolled and treated on E1910 (n=319). Results: Driver genes (n=268) were identified by the mutation-significance detection tool dNdScv or by the presence of pathogenic variants in known cancer genes, with NUP188 identified as a novel driver gene. Recurrently mutated pathways included: B-cell development (46%), cell cycle (44%), epigenetic regulation (30%), other transcriptional regulation (27%), Ras signaling (25%), RNA machinery (17%) and JAK-STAT signaling (8%). A high frequency of high-risk subtypes was observed including BCR::ABL1 (20%), BCR::ABL1-like (18%), low hypodiploid (14%) and KMT2A (12%). Using tSNE analysis, we identified a new cluster of cases (n=20, 3.5%) lacking a known subgroup driver, with overexpression of CEBPA (n=13) or CEBPB (n=7), distinct from CEBPE/ZEB2, termed “CEBP-altered” ALL (CEBPalt). Five of 13 cases with high CEBPA expression harbored an IGH::CEBPA rearrangement and one harbored a RXRA::CEBPA enhancer hijacking alteration. Of the 7 cases with high CEBPB expression, 5 harbored IGH::CEBPB, and two of these had concomitant clonal BCR::ABL1 fusions. To identify additional mechanisms of CEBP deregulation, in situ Hi-C coupled to H3K27 acetylation immunoprecipitation (HiChIP) was performed on 5 cases. Four cases showed evidence of de novo CEBPA enhancer activity. In two cases, we identified novel insertions (12 and 34nt) ~2kb downstream of CEBPA. A novel translocation and enhancer hijacking event between LINC00426 and the 5' UTR of CEBPB was identified in the remaining case. Overall, we confirmed genomic alterations of CEBPA or CEBPB in 16 of 20 cases with available material. Thus, we have identified a new molecular subgroup of adult B-ALL characterized by genomic alterations that drive enhancer hijacking and oncogenic deregulation of CEBPA/CEBPB. Several subgroups were enriched in patients that failed induction chemotherapy (n=62) or were MRD-positive (n=63) compared to those that achieved MRD-negative status (n=194): BCR::ABL1-like (30 vs 14%, p<0.001), KMT2A (18 vs 9%, p=0.03) and BCL2/MYC (5 vs 1%, p=0.06). Conversely, the following subgroups were enriched in patients that achieved MRD-negativity: PAX5alt (6 vs 18%, p=0.002), TCF3::PBX1 (0 vs 5%, p=0.01) and ZNF384 (2 vs 6%, p=0.08) Within each molecular subgroup we compared the survival of patients who achieved MRD-negative status after induction and were randomized to receive blinatumomab plus chemotherapy (n=93) or chemotherapy only (n=91). Although numbers were low, blinatumomab improved relapse-free survival for patients with hyperdiploid, PAX5alt, BCR::ABL1-like and KMT2A ALL compared to chemotherapy alone. Clonal hematopoiesis of indeterminate potential (CHIP)-related gene mutations were identified in 121 of 417 cases analyzed (29% total: somatic 74%, remission 31%, both 5%). TP53 mutations were most frequent (n=65 patients), with the majority identified in patients with low hypodiploid (n=52). Interestingly, patients with CRLF2 rearrangements collectively harbored the highest number of other CHIP gene mutations (n=13), including DNMT3A (n=4), TET2 (n=3) and ASXL1 (n=3). Conclusions:We provide a comprehensive landscape of genomic alterations in adult B-ALL and identify a new group characterized by deregulation of CEBPA/CEBPB (CEBPalt). We also provide insights into the efficacy of blinatumomab in different molecular subgroups of adult B-ALL.

A phase 1 trial of ibrutinib and azacitidine for higher risk myelodysplastic syndromes (University of California Hematologic Malignancies Consortium Study 1503)

Leukemia Research · 2025-06-02 · 1 citations

Hematopoietic Cell Transplantation, Version 3.2025, NCCN Clinical Practice Guidelines In Oncology

Journal of the National Comprehensive Cancer Network · 2025-10-01 · 7 citations

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Cell Transplantation (HCT) provide expert, multidisciplinary recommendations for autologous and allogeneic HCT based on current evidence. The NCCN Guidelines focus on pretransplant recipient evaluation, hematopoietic cell mobilization, conditioning, and the diagnosis and management of graft-versus-host disease (GVHD), a common complication of allogeneic HCT that is associated with significant morbidity. This selection from the NCCN Guidelines for HCT focuses on the diagnosis, workup, and management of acute and chronic GVHD, as well as important supportive care considerations.

A novel application of deep learning (DL)-based MRI with liquid biomarkers for immune effector cell-associated neurotoxicity syndrome (ICANS) after chimeric antigen receptor (CAR) T-cell therapy.

Journal of Clinical Oncology · 2025-05-28

2516 Background: ICANS is a complication of CAR T-cell therapy, yet risk factors and quantitative diagnostic criteria, particularly neuroimaging criteria, remain incompletely characterized. We implemented a novel application of a deep learning (DL)-based MRI approach alongside clinical and liquid biomarkers to better characterize neurotoxicity after CAR T-cell therapy. Methods: We analyzed all patients with non-Hodgkin lymphoma (NHL) or acute lymphoblastic leukemia (ALL) who underwent CAR T-cell therapy at UCSD with a commercial product from 2018-2024. ICANS was graded as per American Society for Transplantation and Cellular Therapy (gr1-4). Variables included stage, performance status, and prior receipt of high-dose methotrexate (HD MTX), intrathecal (IT) chemotherapy, central nervous system (CNS) involvement, CNS-directed radiotherapy (CNS RT), and extracranial RT. Labs obtained pre-infusion, 3 days post-infusion, and during ICANS (or 7 days post-infusion for those without ICANS) were evaluated. Available post-infusion brain MRIs were processed with a 3D U-Net convolutional neural network to quantify T2 FLAIR hyperintensity volumetrics. Linear mixed regression models accounting for zero inflation assessed longitudinal DL-derived FLAIR. Multivariable regression models assessed factors associated with ICANS. Results: Of 163 patients (89% NHL, 11% ALL), 52 had IT chemotherapy, 27 had HD MTX, 24 had prior CNS disease, and 22 had prior CNS RT. Most (106) received axicabtagene ciloleucel (34 tisagenlecleucel, 23 brexucabtagene autoleucel) and most had CRS (133, 82%). ICANS occurred in 73 (45%) at a median of 7 days post-infusion (39 gr1-2, 34 gr3-4). Post-infusion, 21 patients had ³1 brain MRI (93 MRIs total). Baseline factors associated with ICANS were lactate dehydrogenase (LDH; odds ratio [OR] 1.03 p = 0.002) and prior IT chemotherapy (OR 2.5 p = 0.01). There was a trend toward association of gr3-4 ICANS with HD MTX (OR 2.8 p = 0.07). Post-infusion, CRS grade was associated with ICANS (OR 2.8 p < 0.001). LDH (1.02 p = 0.004) and C-reactive protein (OR 1.2 p < 0.001) were elevated during ICANS. Patients with ICANS had significantly greater FLAIR (intercept 23.8 cm³ p < 0.001) and there was increased FLAIR over time across all patients (b = 3.3 cm³ p = 0.05). There was a trend toward association between higher ICANS grade and DL-derived FLAIR (p = 0.09). Conclusions: Here, we demonstrate a novel application of DL-based MRI quantification of ICANS post-CAR T-cell therapy. This metric, along with clinical features, emerged as potential quantitative biomarkers of ICANS. These findings warrant further investigation and have informed a prospective study, including standardized brain MRI pre- and post-infusion, to develop a comprehensive phenotype of neurotoxicity following CAR T-cell therapy.

Three-year analysis of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3

Leukemia · 2025-03-19 · 23 citations

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the US to treat adults aged ≥18 years (≥26 years in the EU) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Brexu-cel showed an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 73% (CR rate 60%) and median overall survival (OS) of 25.4 months in 78 patients with R/R B-ALL after 2 years in ZUMA-3. Here, we report updated outcomes after >3 years median follow-up. As of July 23, 2022, median follow-up in all patients (N = 78) was 41.6 months. Median OS (95% CI) was 25.6 months (1.2-47.0; N = 78) and was 38.9 months (25.4-not estimable) for responders (n = 58), with 9 patients in ongoing remission without subsequent therapies. Five deaths (none deemed brexu-cel-related) occurred since prior data cut. Benefits from brexu-cel were maintained regardless of age, prior therapies, and subsequent allogeneic stem cell transplantation (alloSCT). Subsequent alloSCT was not associated with survival benefit among responders versus responders without subsequent alloSCT. No secondary T-cell malignancies were reported in ZUMA-3 with long-term follow-up.

Outcomes of CAR T-cell therapies after prior treatment with fixed-duration mosunetuzumab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma

Blood · 2025-11-03

Abstract Background: Mosunetuzumab (Mosun) is a CD20xCD3 bispecific antibody (BsAb) evaluated in patients (pts) with B-cell non-Hodgkin lymphoma (B-NHL) in a Phase I/II clinical trial (NCT02500407). Based on this study, intravenous (IV) Mosun is approved for the treatment of pts with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of systemic therapy. The optimal sequencing of available therapies and whether prior exposure to BsAbs impacts the effectiveness of subsequent CD19-targeted chimeric antigen receptor (CAR) T-cell therapies remain unclear. Limited data suggest that the efficacy of CAR T-cell therapies is preserved in pts with large B-cell lymphoma (LBCL) who received prior BsAbs (Crochet et al. Blood 2024). Here, we present a US multicenter, retrospective, case series to evaluate the outcomes of pts with R/R B-NHL treated with CAR T-cell therapy after Mosun. Methods: Pts from all dose-escalation and expansion cohorts in a Phase I/II clinical trial (NCT02500407) were included in this analysis. Efficacy and safety outcomes were investigated in pts with R/R B-NHL who received CAR T-cell therapy for the first time following Mosun treatment. Eligible pts were treated with autologous CAR T-cell therapy between December 8, 2015 and August 9, 2021. Results: At data cut-off (May 13, 2024), 48 pts with R/R B-NHL had received CAR T-cell therapy following Mosun treatment; available data from 22 pts are presented here. Median age was 67 years (range: 52–81) and 72.7% of pts were male. Thirteen pts had aggressive B-NHL (LBCL, n=6; mantle cell lymphoma [MCL], n=5; transformed FL [trFL], n=2) and 9 pts had indolent B-NHL (all FL). Pts had a median of 4 prior therapies (range: 2–7) before Mosun. Twenty-one pts received Mosun IV and 1 received a subcutaneous formulation. Investigator-assessed best overall response (BOR; complete response [CR] or partial response) to Mosun was 50.0% (4/8 pts; CR, n=0) in pts with LBCL/trFL, 60.0% (3/5 pts; CR, n=2) in pts with MCL, and 66.7% (6/9 pts; CR, n=2) in pts with FL. The median duration of Mosun treatment was 3.0 months (mo; range: 1.4–5.7), 4.8 mo (range: 1.9–7.7), and 5.1 mo (range: 1.4–13.5) in pts with LBCL/trFL, MCL, and FL, respectively. Median time from the initiation of Mosun to the administration of CAR T-cell therapy was 11.8 mo (range: 2.3–30.5). Median number of therapies prior to CAR T-cell therapy was 5 (range: 2–11); Mosun was the last line of treatment before CAR T-cell therapy in 12 (54.5%) pts. Two (9.1%) pts received bendamustine within 12 mo prior to leukapheresis and 3 (13.6%) pts received bridging therapy (radiation [RT], n=2; RT and venetoclax, n=1). The CAR T-cell therapies received were axicabtagene ciloleucel (n=12), brexucabtagene autoleucel (n=3), tisagenlecleucel (n=2), lisocabtagene maraleucel (n=1), and an investigational CD19-targeted CAR T-cell therapy (n=4). Twelve (54.5%) pts received CAR T-cell therapy in a clinical trial. At the site-specific data cut-off (City of Hope: July 12, 2024; MD Anderson: February 11, 2025; Fred Hutchinson: February 26, 2025; and Washington University: May 30, 2025), in pts with LBCL/trFL the BOR rate with CAR T-cell therapy was 87.5% (7/8; CR, n=6); duration of response (DOR) ranged from 1.4 to 52.3 mo, with 2 responses ongoing. In pts with MCL, the BOR rate was 40.0% (2/5; CR, n=2); DOR ranged from 22.8 to 36.3 mo, with 1 response ongoing. In pts with FL, the BOR rate was 100% (9/9; CR, n=6); DOR ranged from 3.4 to 61.1 mo, with 5 responses ongoing. During follow-up, 9 pts in the overall cohort died: 5 due to lymphoma and 1 each due to acute renal failure, infection, pneumonia, and sepsis. Cytokine release syndrome (CRS) after CAR T-cell therapy was observed in 68.2% (15/22) of pts, all cases were low grade (Gr; Gr 1, n=8; Gr 2, n=7). Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 36.4% (8/22) of pts (Gr 1, n=2; Gr 2, n=4; Gr 3, n=1; Gr 4, n=1). By data cut-off, CRS was resolved in all pts and ICANS in 7/8 pts. Conclusions: This real-world multicenter analysis suggests that prior Mosun treatment does not impair the efficacy of subsequent CAR T-cell therapy in pts with R/R B-NHL, with the safety profile consistent with previously published data. These results support CAR T-cell therapy as a viable treatment option following BsAb treatment. Further studies are needed to fully characterize and validate the efficacy and safety of CAR T-cell therapy after BsAbs such as Mosun.