Pasquini, Marcelo C.

Abstract Introduction: Liso-cel, an autologous, CD19-directed CAR T cell product, has demonstrated consistent efficacy in a broad population of pts with B-cell malignancies, including R/R LBCL. Its well-established safety profile has made OP delivery commonplace. This, combined with recent changes to postinfusion monitoring requirements, offers pts the potential for greater access to care. Here, we describe real-world safety and effectiveness outcomes for pts with R/R LBCL who received liso-cel as standard of care (SOC) therapy in the inpatient (IP) or OP setting. Methods: This was an observational study of pts in the US with R/R LBCL who received commercial liso-cel as second-line (2L) or later treatment (tx) in the IP or OP setting between 02/2021 and 02/2025 and had ≥1 postinfusion assessment reported in the Center for International Blood & Marrow Transplant Research (CIBMTR). Safety outcomes included rates of AEs of special interest and nonrelapse mortality (NRM). Postinfusion hospitalizations in the OP group were also assessed. Effectiveness outcomes included ORR, CR rate, duration of response (DOR), PFS, and OS. All results are reported descriptively. Results: Of 1116 eligible pts, 34% (n=375) were intended for OP tx, as reported to the CIBMTR, including 82 of 195 (42%) pts who received liso-cel as 2L tx. Among pts treated in the IP vs OP setting, median (range) age was 71.5 y (21.5–91.2) and 69.8 y (25.0–86.1), respectively, and most pts were male (59% and 61%). Proportions of pts with high-grade B-cell lymphoma (16% and 12%), ≥2 extranodal involvement sites (26% and 26%), and secondary CNS involvement (5% and 4%) were similar for the IP and OP groups, respectively. In contrast, 48% vs 37% of pts in the IP vs OP groups, respectively, had elevated LDH before infusion and 10% vs 3% had ECOG PS ≥2. One or more comorbidities were reported for 72% and 65% (including cardiac, 36% and 32%; pulmonary, 30% and 26%; active infections requiring ongoing tx, 6% and 3%) of pts in the IP and OP groups, respectively. Median (range) number of prior lines of therapy was 3 (1–13) in the IP group and 3 (1–16) in the OP group. Use of bridging therapy was reported in 65% of the IP group and 62% of the OP group. Median (95% CI) follow-up for this study was 12.7 mo (12.5–13) in the IP group and 12.6 mo (12.4–12.8) in the OP group. Safety was similar in both settings; any-grade CRS was reported in 52% of IP vs 49% of OP setting pts, with low rates of grade 2 CRS (15% vs 11%) and grade ≥3 CRS (3% vs 2%) in both groups. Any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) rates were also similar in pts in the IP vs OP setting (28% vs 23%), with low rates of grade 2 ICANS (5% vs 4%) and grade ≥3 ICANS (10% vs 8%). Prolonged cytopenia (grade 4 thrombocytopenia and/or neutropenia at 30 d after infusion) was reported in 12% and 14% in the IP and OP groups; clinically significant infections at any time after infusion occurred in 48% of IP and 42% of OP setting pts. In the IP and OP groups, 37% and 30% of pts died, most commonly due to PD (25% and 21%) and the NRM rates at 12 mo were 7.1 (95% CI, 5.2–9.4) and 4.1 (95% CI, 2.2–6.8). Among OP setting pts, 46% were not hospitalized after infusion; of those hospitalized after OP infusion, median (IQR) time to hospitalization was 5 d (3-8) and duration of stay was 5 d (3-9). Response rates were high in both the IP (ORR, 80% [95% CI, 77–83]; CR rate, 70% [95% CI, 66–73]) and OP setting (ORR, 83% [95% CI, 79–87]; CR rate, 74% [95% CI, 69–79]). At ~12 mo follow-up, median (95% CI) DOR was not reached (NR; NR–NR) in either group with 12-mo DOR rates of 59% (95% CI, 54–63) and 63% (95% CI, 56–69), respectively. Median (95% CI) PFS was 11.8 mo (8.8–NR) in the IP group vs NR (NR–NR) in the OP group, with 12-mo PFS rates of 49% (95% CI, 45–53) and 56% (95% CI, 50–61), respectively. Median (95% CI) OS was NR (NR–NR) in both groups with 12-mo OS rates of 65% (95% CI, 61–68) in the IP group and 74% (95% CI, 68–78) in the OP group. Conclusions: These results continue to demonstrate that one-time tx with liso-cel results in deep, clinically meaningful efficacy in the SOC setting across a broad population of pts with R/R LBCL. Despite the few differences reported in baseline characteristics, outcomes were consistent among pts treated in the IP and OP care settings. The well-established safety profile of liso-cel is conducive to OP tx, allowing ~50% of pts to remain out of the hospital postinfusion.

Abstract Introduction: Axi-cel, an autologous anti-CD19 CAR T-cell therapy has shown high and durable response rates and a manageable safety profile among R/R FL pts in the ZUMA-5 trial (Jacobson et al. 2022; Neelapu et al. 2024). Evidence from real-world data showed favorable early outcomes in a broader population using CIBMTR data, with comparable outcomes by ZUMA-5 eligibility, age, lines of therapy (LOT), and prior bendamustine (benda) use (Jacobson et al. 2023). This study investigated long-term outcomes and the association between age, performance status, comorbidities, and therapies given prior to infusion among R/R FL pts treated with axi-cel. Methods: Pts with R/R FL who received commercial axi-cel between 03/2021–10/2023 in the US were identified from the CIBMTR® registry; pts without consent, with prior non-transplant cellular therapy, and FL grade 3B or 3A/3B unspecified or unknown were excluded. Descriptive analyses were done among all pts and by age at infusion (<65 vs ≥65 y), Karnofsky performance score (KPS), presence of hepatic, cardiovascular (CV), or moderate to severe pulmonary comorbidities, prior treatments (benda pre-leukapheresis, autologous hematopoietic stem cell transplant [autoHSCT]), and lymphodepletion (LD) therapy. Multivariable (MV) Cox and logistic regression were used to adjust for confounders. Results: In total, 238 pts from 68 centers were included (data cut-off October 2024). Median age at infusion was 61 yr (range, 29-83; ≥65 yr, 38%), and 79% were non-Hispanic White. KPS of pts was ≤70% (11%), 80% (35%), or 90-100% (54%); 2% had ECOG ≥2. Most (75%) had ≥1 clinically significant comorbidity (hepatic, 6%; CV, 15%; pulmonary, 18%). Median (min, max) prior LOT was 4 (1,13); 74% received benda pre-leukapheresis, and 6% had benda LD therapy. At a median follow-up of 24.1 months, objective response rate (ORR) was 96% (complete response [CR] rate, 91%). The 2-yr (95% CI) DOR, PFS, and OS were 70% (63-77), 64% (57-71), and 84% (78-89) respectively. Grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 4% and 18% of pts (any grade, 74% and 42%), respectively. Prolonged cytopenias by day 30 occurred in 14% of pts (neutropenia [10%] and thrombocytopenia [8%]) while 29% had clinically significant infections at 6 months. Second primary malignancies occurred in 16 pts (7%), with 7 (2%) being therapy-related myeloid neoplasm. The leading primary causes of death (n=34) were relapse/progression (10; 29%), organ failure (7; 21%), and infection 5 (15%). Cumulative incidence of non-relapse mortality at 2-yr was 9%. Outcomes were generally comparable among age, autoHSCT, and comorbidity subgroups. However, effectiveness outcomes differed by prior benda use (Yes vs No): ORR (95% vs 98%); CR (88% vs 98%); DOR (65% vs 89%), PFS (58% vs 84%), and OS (82% vs 91%) at 2 years. By LD therapy (single agent benda vs cyclophosphamide + fludarabine [Cy + Flu]): the ORR was 93% vs 96%; CR rate was 57% vs 93%. On MV analysis, prior benda use was associated with (OR/HR [95% CI]): worse CR (0.02 [<0.01-0.43]), DOR (3.69 [1.51-9.02], and PFS (2.21 [1.12-4.38]). Pts given benda LD therapy had (OR/HR [95% CI]): worse CR rate (0.02 [<0.01-0.16]), DOR (7.59 [2.33-24.72]), and PFS (4.89 [1.79-13.39]) compared to those who received Cy + Flu. CRS and ICANS were lower among those with prior benda use (Yes vs No): any-grade CRS (70% vs 87%); Grade ≥3 CRS (3% vs 8%); any-grade ICANS (36% vs 61%); and grade ≥3 ICANS (17% vs 25%). By LD therapy (single agent benda vs Cy + Flu): the Grade ≥3 CRS and ≥3 ICANS were 0% vs 5% and 7% vs 19% respectively. Any-grade ICANS was higher among those aged ≥ 65 yr vs <65 yr (53% vs 35%). On MV analysis, pts who had prior benda use were less likely to have any-grade CRS (0.30 [0.12-0.75]), and any-grade ICANS (0.23 [0.11-0.50]. Pts ≥ 65 yr had higher any-grade ICANS (2.31 [1.18 – 4.50]). Summary/Conclusion: This long-term follow up of axi-cel in R/R FL shows durable responses and manageable safety similar to ZUMA-5. Outcomes among the elderly and those with comorbidities were generally comparable to the overall R/R FL population. Although benda use pre-leukapheresis was associated with less durable responses, we were unable to determine whether this association is limited to use close to axi-cel infusion, as data on timing of use was unavailable. The associations for benda LD should be interpreted with caution given the small sample size.

Abstract The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T-cell (CAR-T) therapy is not well established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017 to 2020 were selected from the Center for International Blood and Marrow Transplant Research registry. Patients were randomly assigned to training or validation cohorts. Comorbidities given weighted scores comprised the CT-CI, which was then validated for overall survival (OS) prognostication. A total of 1916 patients from 97 medical centers were included, with a median age of 64 years (19-91 years). About 70% of patients had comorbidities, such as cardiac disease (12%); diabetes (14%); hepatic dysfunction (mild, 8%; moderate to severe, 2%); psychiatric disturbance (18%); and pulmonary dysfunction (moderate, 15%; severe, 12%). The CT-CI was calculated, stratified patients in 3 categories, and was associated with increased mortality. Patients with higher CT-CI scores had worse OS (CT-CI 1: hazard ratio [HR], 1.37 [95% confidence interval [CI], 1.16-1.62; P< .001]; CT-CI 2: HR, 1.49 [95% CI, 1.17-1.89; P = .001]; CT-CI ≥ 3: HR, 2.55 [95% CI, 1.90-3.42; P< .001]). Higher CT-CI scores predicted treatment-related mortality and relapse. There was no correlation between the CT-CI score and CAR-T–related toxicities. The novel CT-CI score stratifies the effect of patient comorbidities on survival after CAR-T therapy and can be used for clinical decision-making and treatment selection in high-risk populations. However, comorbidities and fear of increased toxicity should not preclude patients from this effective therapy.

Abstract Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T-cell therapy approved for relapsed/refractory mantle cell lymphoma (R/R MCL). Here, we report real-world effectiveness and safety outcomes of brexu-cel in a prospective study of patients with R/R MCL, including subgroups based on prior treatment with Bruton's tyrosine kinase inhibitor, bendamustine, or autologous hematopoietic cell transplant (auto-HCT) and number of prior therapy lines, using Center for International Blood and Marrow Transplant Research registry data. A total of 476 patients with R/R MCL who received brexu-cel between July 2020 and December 2022 were included in the analysis. With a median follow-up of 13.5 months, the overall response rate was 91% and complete response rate was 82%. One-year overall survival and progression-free survival rates were 76% and 63%, respectively. One-year cumulative incidence of nonrelapse mortality was 8%. Prior auto-HCT was associated with better duration of response within 6 months after infusion (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.28-0.85) but greater risk of immune effector cell–associated neurotoxicity syndrome (odds ratio [OR], 1.66; 95% CI, 1.06-2.60). Prior bendamustine was associated with increased risk of prolonged thrombocytopenia (OR, 1.90; 95% CI, 1.13-3.21). In patients with 1 to 2 prior therapy lines, relapse or progression was less frequent compared with those with ≥3 prior lines (HR, 0.64; 95% CI, 0.42-1.00). Collectively, our results suggest that real-world outcomes with brexu-cel were consistent with those of the ZUMA-2 trial, regardless of prior therapy type or number of prior therapy lines.

7023 Background: Axi-cel is an autologous chimeric antigen receptor (CAR) T-cell therapy approved for adults with R/R LBCL after ≥ 1 prior line of therapy (LoT). Adverse events, such as cytokine release syndrome (CRS) and neurologic events (NEs), may deter centers from using axi-cel in an outpatient (OPT) setting, though individual centers have observed comparable safety and effectiveness in OPT and inpatient (IPT) care (Furqan et al. Blood Adv . 2024). Here, we present safety and effectiveness outcomes of axi-cel by intention to treat in OPT and IPT settings in a multicenter real-world dataset. Methods: Pts receiving axi-cel for R/R LBCL in the US from 01/2021-07/2023 with data in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry were eligible for analysis. Pts with prior allogeneic transplant or unknown intended care setting were excluded. Of potential pts, 119 OPT pts were identified from 29 centers where an increasing trend was seen (9.6% of pts in 2021 were OPT, 13.5% in 2022, 22.8% in 2023). Pts were matched to 119 IPT pts by propensity score matching on age, sex, comorbidities, lactate dehydrogenase (LDH), bulky disease, prior LoT, chemosensitivity, and infusion year (see table). Results: OPT pts had median age of 63 y (25% ≥ 70), 66% were male, and 67% had ≥ 1 comorbidity. Half (50%) had elevated LDH and 73% had 1 prior LoT. Bulky disease was reported in 3%, and 60% had chemo-resistant disease. Outcomes were analyzed at median follow-up of 12 mo. Safety and effectiveness outcomes were similar between OPT and IPT pts (see table). In multivariate analyses, no differences were found between intended care setting and CRS (odds ratio [OR] 1.09 [95% CI 0.51-2.35]), CRS Gr ≥ 3 (OR 0.57 [0.12-2.60]), NEs (OR 1.14 [0.65-2.00]), or NEs Gr ≥ 3 (OR 0.98 [0.48-2.00]). Among OPT pts, 24% and 50% did not require hospital admission within 30 d and 3 d, respectively. In pts aged ≥ 70 y, only any Gr NEs were higher in the OPT group. Conclusions: After matching on key factors that may be used to select pts for OPT infusion, outcomes were comparable between intended care settings. These findings corroborate prior results and support the consideration of axi-cel in appropriate OPT care settings. Outcomes between matched pts with R/R LBCL receiving axi-cel intended for OPT or IPT. OPT (n=119) a IPT (n=119) a CRS any Gr / Gr ≥ 3 83 (75−89) / 3 (<1−7) 83 (74−89) / 4 (1−10) NE any Gr / Gr ≥ 3 47 (38−57) / 19 (12−27) 46 (37−56) / 21 (14−30) Overall / complete response rates 78 (69−85) / 68 (59−76) 76 (67−83) / 62 (52-70) Duration of response @ 12 mo 64 (52−74) 69 (58−78) Progression-free survival @ 12 mo 53 (43−62) 53 (43−61) Overall survival @ 12 mo 71 (61−78) 72 (62−79) Non-relapse mortality @ 12 mo 6 (2−11) 4 (1−8) Hospital admission within 30 days of infusion / median duration (range), d 76 (67−83) / 9 (2−53) Not Applicable a Percent (95% CI) unless otherwise specified.

Abstract Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel. The impact of V2Vt (&lt;28 days vs ≥28 to &lt;40 days vs ≥40 days) on effectiveness and safety outcomes was evaluated in patients treated with axi-cel enrolled in a post-authorization safety study using the Center for International Blood and Marrow Transplant Research data. SLR and meta-analysis showed that patients treated with axi-cel had the shortest median V2Vt (30.6 days) compared with tisa-cel (48.4 days) or liso-cel (35.9 days). Real-world analysis of patients treated with axi-cel demonstrated that V2Vt ≥40 days was associated with significantly lower complete response rate than V2Vt &lt;28 days (odds ratio [OR], 0.61) or ≥28 to &lt;40 days (OR, 0.66) and significantly worse overall survival than V2Vt &lt;28 days (hazard ratio [HR], 1.33) or ≥28 to &lt;40 days (HR, 1.36). Higher prolonged thrombocytopenia rates were observed in patients with axi-cel V2Vt ≥28 to &lt;40 days or ≥40 days compared with &lt;28 days (OR, 1.44 or 1.95, respectively). Together, these results show the impact of V2Vt on patient outcomes with axi-cel therapy and that earlier infusion with CD19-CAR therapies may be beneficial.

Background: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are known safety concerns following chimeric antigen receptor (CAR) T-cell therapy. Axi-cel, a CAR T-cell therapy approved in the US for adults with R/R LBCL after ≥ 1 line of prior therapy (2L+), has been administered in the outpatient setting, where a common cause for post-infusion hospital admissions were CAR T-cell-related toxicities (Furqan et al., 2024). Due to reimbursement policies in the US, patients at higher risk for safety events requiring inpatient care within 3 days of infusion may not be ideal candidates for outpatient care. We sought to identify what pre-infusion characteristics may put patients more at risk for developing early CRS and ICANS after axi-cel. Methods : Patients receiving axi-cel for R/R LBCL 2L+ between 01/2021−10/2023 registered in the Center for International Blood and Marrow Transplant Research (CIBMTR) observational database were potentially eligible for analysis. Patients with prior non-transplant cellular therapy or missing data for analysis were excluded. Primary endpoints were onset of early CRS and early ICANS, defined as an any grade event within 3 calendar days of axi-cel infusion (date of infusion is defined as Day 0 and onset of CRS/ICANS before the end of Day 3 is an early event). Early Grade ≥ 2 and early Grade ≥ 3 CRS and ICANS (onset of CRS/ICANS before the end of Day 3 and maximum Grade ≥ 2 and ≥ 3 per ASTCT Criteria) were also evaluated. Patient demographics, ECOG PS, comorbidities, disease characteristics at diagnosis and prior to infusion, line of therapy (LoT), lab assessments prior to infusion, and infusion-related attributes were evaluated by univariate screening and multivariable regression for development of early CRS or early ICANS. Results: A total of888 patients from 105 centers were included in the analysis. Median age was 63 years (45% ≥ 65 years) and 66% were male. At LBCL diagnosis, 22% of patients had a histological transformation. Prior to infusion, 5% of patients had ECOG PS ≥ 2 and 70% had at least 1 clinically significant comorbidity. Half (50%) of patients received axi-cel with 1 prior LoT (2L) and 10% of patients underwent a prior autologous hematopoietic cell transplant. Median time from leukapheresis to infusion was 30 days (interquartile range [IQR] 27−34). Bridging therapy of any type was administered in 59%, and systemic bridging therapy in 48%, of patients and 14% of patients were intended to be treated in the outpatient setting. Thirty percent of patients had chemo-sensitive disease prior to infusion. Median follow-up post-infusion was 12.3 months (range 3−38). Median time to onset of CRS was 4 days (IQR 2−6) and 84% of patients experienced CRS at any time. Early any grade (Grade ≥ 3) CRS was observed in 47% (3%) of patients. In the multivariate analysis of early any grade CRS, only prior LoT (≥ 2 vs 1) was associated with lower risk (OR 0.71; 95% CI 0.55−0.94), but this association was not seen in the analyses of early Grade ≥ 2 nor early Grade ≥ 3 CRS. Notably, 47% and 52% of patients with ≥ 2 vs 1 prior LoT, respectively, only experienced early Grade 1 CRS (defined as fever only). In the analysis of early Grade ≥ 3 CRS, only ECOG PS 0−1 was associated with lower risk vs patients with ECOG PS ≥ 2 (OR 0.17; 95% CI 0.06−0.48). Median time to onset of ICANS was 7 days (IQR 5−9) and 47% of patients experienced ICANS at any time. Early any grade (Grade ≥ 3) ICANS occurred in 9% (5%) of patients. After multivariate adjustment, age &lt; 65 vs ≥ 65 (OR 0.38 [95% CI 0.23−0.62]) and 1 vs ≥ 2 prior LoT (OR 0.58 [95% CI 0.36−0.95]) were associated with lower risk of early any grade ICANS. Age &lt; 65 vs ≥ 65 was also associated with lower risk of early Grade ≥ 3 ICANS (OR 0.31 [95% CI 0.15−0.61]), as was ECOG PS 0−1 vs ECOG PS ≥ 2 (OR 0.30 [95% CI 0.11−0.83]). Comorbidities were evaluated and no significant associations with early CRS nor early ICANS were found. Conclusions: This analysis of readily available clinical variables in a real-world contemporary cohort of patients treated with axi-cel demonstrates that younger patients and patients with better ECOG PS have lower risk of early CRS and early ICANS. Axi-cel in 2L setting, vs 3L+, is associated with lower risk of early any grade ICANS and comparable early Grade ≥ 2 CRS, but a higher risk of early fever. These results further enable a more informed decision of patient selection for physicians, which is critical for the success of outpatient administration.

Background: 24-hour urine (24HRU) assessments are a key component of International Myeloma Working Group (IMWG) response criteria for multiple myeloma (MM) and are requested longitudinally in clinical trials even if not routinely used in real-world practice. Several analyses have suggested a limited role for 24HRU if serum immunofixation or free light chain (LC) testing is abnormal (Dejoie Blood 2016, Lahuerta Blood 2023). Adopting urine-free response criteria (with 24HRU removal from every level of IMWG response) may change responses in &lt;5% of patients (Natsuhara et al, Leuk Lymph 2023) but not have been studied in terms of progression-free survival (PFS) in a larger population. Methods: This was a secondary analysis of data from the Phase 3 BMT CTN 0702 (STaMINA) trial (Stadtmauer et al, JCO 2019) studying post-autologous stem cell transplantation (ASCT) strategies. Only patients evaluable for Day +56 response following ASCT were included, and patients with progressive disease (PD, n=8) at this timepoint were excluded. Post-ASCT responses relative to diagnosis were calculated by two sets of criteria. First, traditional responses were calculated per IMWG criteria (Kumar et al, Lancet Onc 2016) as stable disease (SD), partial response (PR), very good PR (VGPR), or complete response (CR, including stringent CR). Second, urine-free response assessments were calculated as follows: negative 24HRU immunofixation no longer required for CR, 24HRU M-protein &lt; 100 milligrams (mg) per day no longer required for VGPR, and no 24HRU M-protein thresholds (e.g., &lt; 200 mg per day or &gt; 90% reduction) required for PR. PFS was estimated (using PD by traditional IMWG criteria or death as events) using proportional hazard models. Results: Of 636 evaluable patients (84% of all BMT CTN 0702 participants), LC-only disease was noted in 18.9% (n=120). Pre-enrollment 24HRU testing at diagnosis was done in 28.9% of patients (n=184). IMWG responses were as follows: CR, 29.4% (n=187) traditional vs 29.7% (n=189) urine-free; VGPR, 37.0% (n=235) traditional vs 36.6% (n=233) urine-free; PR, 30.7% (n=195) for both; SD, 3.0% (n=19) for both. A total of 4 responses (0.6%) changed with urine-free criteria. Three patients were ‘upgraded’ (VGPR to CR, n=2, PR to VGPR, n=1) because 24HRU requirements for CR/VGPR were no longer required. One patient without a measurable serum paraprotein was ‘downgraded’ from a traditional VGPR (with negative 24HRU immunofixation) to a urine-free PR based on LC-only criteria. Among the subset of 184 patients with 24HRU electrophoresis results at diagnosis, there were no differences between traditional and urine-free IMWG responses. Median PFS and 95% confidence intervals (CI) were the same at each depth of both traditional and urine-free criteria: 63.0 months (50.8 - 71.4 months) for CR, 49.6 months (42.6 - 55.1 months) for VGPR, 44.9 months (37.2-54.8 months) for PR, and 34.4 months (14.0-51.5 months) for SD. Urine-free IMWG criteria were highly prognostic for PFS (p = 0.006, 95% CI 1.05-1.36). The achievement of urine-free CR vs urine-free ≤CR was also prognostic (p = 0.005, 95% CI 0.54 - 0.89). Urine-free VGPR vs urine-free ≤VGPR was of borderline significance (p = 0.102, 95% CI 0.66 - 1.04), with median PFS 53.8 months (48.0 - 57.6 months) vs 44.6 months (36.3 - 54.7 months) respectively. Discussion: In this secondary analysis of a Phase 3 trial, omitting 24HRU assessments from IMWG criteria changed &lt;1% of responses and had no impact on PFS prediction at any response depth. 24HRU assessments had been performed for less than a third of patients as standard of care prior to study entry, underscoring its infrequent use outside of trials. Urine-free IMWG assessments would reduce time toxicity and discomfort for patients, particularly for those with limited dexterity. If implemented in trials, they would also simplify study logistics and lower operational costs. Outside of situations such as AL amyloidosis where 24HRU assessments remain critical or for patients with urine as their only measurable MM biomarker, our results support the removal of 24HRU assessments from future iterations of IMWG response criteria. Funding: Grants #U10HL069294 and #U24HL138660 to the BMT CTN from the NHLBI and the NCI; contributions by Celgene Corporation and Millennium Pharmaceuticals, Inc.; funding by The Alliance for Clinical Trials in Oncology, the ECOG-ACRIN Cancer Research Group and SWOG.

Abstract Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell–associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov.