Lin, Yi

CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). We describe overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety, with a median study follow-up of 61.3 months. For the 97 treated patients, median OS was 60.7 months (95% CI, 41.9 to not estimable). One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment. Twelve of these patients treated at a single center underwent serial minimal residual disease (MRD) and positron emission tomography-computed tomography assessments, and all (100%) were MRD-negative (at least 10 −5 threshold) and imaging-negative at year 5 or later after cilta-cel. Baseline characteristics, including the presence of high-risk cytogenetics and extramedullary disease, were generally comparable for the 32 patients who were progression-free for ≥5 years versus patients who had progressive disease by year 5. A trend of lower baseline tumor burden, higher fraction of naïve T-cells in the cilta-cel drug product, higher T cell-to-neutrophil ratio, higher hemoglobin and platelets at baseline, and higher effector-to-target ratio were associated with ≥5-year progression-free status. The safety profile of cilta-cel remained consistent with previous reports. To our knowledge, our data provide the first evidence that cilta-cel is potentially curative in patients with RRMM.

1652 Background: Tarlatamab is a bispecific T-cell engager targeting DLL3 that has shown promise as a therapy in small cell lung cancer. Administering tarlatamab requires careful consideration of immune-related adverse events (AE), including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Prescribing information recommends patients to be monitored for 22-24 hours in an appropriate healthcare setting for cycle 1 (C1), days 1 and 8. At Mayo Clinic in Rochester MN (MCR), tarlatamab is initially administered in a hospital-based outpatient (HBO) setting utilizing an innovative remote patient monitoring system (RPM). In this study, we describe our RPM process and patient outcomes thus far. Methods: We retrospectively reviewed records of patients treated with tarlatamab from August through December 2024. All patients received tarlatamab in the HBO setting and were enrolled into RPM for C1, days 1–10. Patients attended daily HBO visits on days 1–3 and 8–10 of C1 and were required to stay within 30 minutes of the hospital with a 24-hour caregiver for 48 hours following infusion days in C1-2. Data on patient characteristics, frequency of RPM alerts, escalations, rate of CRS & ICANS, and need for hospitalizations were reported using descriptive metrics. Results: As part of RPM, patients are provided with a kit containing preconnected Bluetooth-enabled devices to measure vital signs (VS), including blood pressure (BP), heart rate (HR), temperature (T), and pulse oximetry (SpO2). The kit also includes a cellular-enabled tablet for electronic ICANS questionnaires, which upload directly into our electronic medical record system. Patients are required to log VS four times daily, monitored in real-time by a centralized virtual RPM nursing (RN) team. Embedded decision trees trigger alerts, prompting the RN team to contact patients and follow care pathways for escalations as needed. Among the 16 patients treated, the median age was 68 years, and the median ECOG PS was 1. During the 10-day RPM period, a total of 2,233 VS entries were recorded. Of these, 88% (14/16) of patients had alerts triggered, with a median of 2 alerts per patient. Alerts were mostly for out-of-range systolic BP (56%), HR (56%), and T (25%), with none for SpO2. The RN team escalated alerts in 50% (8/16) of the patients. Overall, 38% (6/16) of patients were managed entirely in the HBO setting. Among the 63% hospitalized, 56% had CRS limited to grade (G) 2, and 31% had ICANS limited to G3. Two patients were hospitalized for other indications. The mean length of stay was 2.6 days, with no ICU admissions. Conclusions: Our experience shows that frequent monitoring required with tarlatamab can be safely and effectively executed in an outpatient setting with the utilization of an RPM system. It can potentially minimize the burden of hospitalizations for patients and the healthcare system.

e13622 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized treatment of hematologic malignancies; however, severe toxicities like cytokine release syndrome (CRS) remain a limitation to broader utilization. Using a large dataset of patients treated with CAR-T, we developed a machine learning (ML) model leveraging multi-model patient characteristics to predict the risk of CRS onset with clinically meaningful lead times. Methods: A prospectively maintained dataset of CAR-T patients treated at Mayo Clinic was used. Baseline disease/patients characteristics, labs, ECG, echocardiogram, and vital signs (including data from remote patient monitoring program) were collected. A 24-hour rolling window was used to generate daily averages, maximum, minimum, and deltas for each parameter. ECG and echocardiogram data were forward-imputed; vital signs and labs were not imputed. Each day-post-infusion served as a potential event (CRS onset vs. no CRS). A gradient boosting classifier was trained and tested on a subset of patients (n = 351) using 1,000 bootstrap iterations, evaluating 24-, 48-, and 72-hour lead times. Shapley-based feature importance guided simplification to an 11-feature model, externally validated on an independent cohort (n = 51). Models’ performance assessed using the area under the receiver operating characteristic curve (AUC). Results: A total of 402 patients treated with CAR-T were examined. Median age was 64 years and 36% were female. Primary diagnosis was B-cell lymphoma (n = 240) or multiple myeloma (n = 162). A total of 226,332 vital sign measurements and 372,871 lab values, as well as ECG and echocardiogram data, were collected for 30 days post-infusion. Overall, 79.8% of patients experienced CRS within 30 days. The full ML model demonstrated AUCs of 0.90 (95% CI 0.86–0.93), 0.83 (95% CI 0.77–0.88), and 0.82 (95% CI 0.77–0.87) for 24-, 48-, and 72-hour predictions of CRS, respectively. Including “day of CRS onset post CAR-T” as a feature improved the 72-hour AUC to 0.87 (95% CI 0.83–0.90). A model restricted to vital signs alone showed AUCs of 0.88, 0.75, and 0.71 for 24-, 48-, and 72-hour horizons. An 11-feature model—focusing on temperature, blood pressure, fibrinogen, CRP, serum sodium level, QRS interval, and lymphocyte counts—maintained high accuracy at 24 hours (AUC 0.90, 95% CI 0.86–0.93) and was validated externally using an independent dataset with an AUC of 0.92. Conclusions: Our ML model provides a reliable approach for predicting if/when CRS will occur, with up to three days of lead time before clinical manifestation, offering an opportunity for proactive management. The robust performance of a parsimonious 11-feature model supports practical adoption across clinical settings and real-time risk stratification to enhance patient safety. Prospective validation and integration into clinical workflows will be critical to translating these findings into practice.

7522 Background: Movement and neurocognitive treatment emergent adverse events (MNTs), cranial nerve palsies (CNPs) and immune-effector cell enterocolitis (IEC-EC) are late onset toxicities associated with cilta-cel and are associated with significant morbidity and mortality. We aimed to identify predisposing risk factors to allow for formulating risk-reduction strategies. Methods: Retrospective study of MM pts who received FDA approved cilta-cel at Mayo Clinic between Feb 2022-Dec 2024. Interrogated factors included demographics, disease and treatment characteristics, and selected lab values at different time points. In odds ratio (OR) analyses, pts were divided by toxicity type (1) No delayed toxicity (2) MNT (3) IEC-EC without MNT (4) isolated CNP. Differences between pts in the MNT, IEC-EC and CNP groups were compared separately in a pairwise manner vs. those with no delayed toxicity. Results: Of 235 pts, 26 (11%) had delayed toxicity [MNT = 8 (3%), IEC-EC = 9 (4%), CNP = 14 (6%)]; 3 pts had both MNT/IEC-EC and 2 had both CNP/IEC-EC. Median onset from CAR-T infusion for MNT, IEC-EC and CNP was 19 (range 8-96), 106 (35-169) and 21 (7-43) days respectively. Of 164 evaluable pts, those who had ICANS had increased odds for any delayed toxicity (OR 4.7; 95% CI 1.6-13.8). Pts who had ICANS (OR 7.7; 1.6-36.9), HLH/MAS (OR 6.2; 1.1-6.7) and Ferritin >400mcg/L at time of lymphodepletion (OR 6.3; 1.5-32) had increased odds for MNTs. Pts who received alkylator-based bridging therapy had increased odds (OR 6.1; 1.1-35) for IEC-EC. Analysis of serial post-CAR infusion lab values showed that peak ALC was the most significant variable with differences between groups shown in table. Median time to peak ALC was 12 days (IQR 11-13). ROC analysis determined peak ALC >3 x 10 9 /L as a meaningful cut point. Pts with peak ALC >3.0 x 10 9 /L had increased odds of developing any delayed toxicity (OR 9.3; 3.5-29.3), MNT and CNP (table). Absolute risk of any delayed toxicity was 33% in pts with peak ALC >3 x 10 9 /L vs 5% without. At this threshold, number needed to treat was 3.6. Conclusions: Real-world data shows that cilta-cel associated delayed toxicity is seen in ~10% of patients, with specific toxicity rates between 4-8%. Factors associated with these toxicities predominantly occur in the post CAR-T infusion period. Given that ALC expansion in the first 2 weeks correlate with CAR-T expansion, peak ALC is potentially predictive of toxicity and 3 x 10 9 /L may be an interventional threshold for primary prophylaxis. Peak ALC by toxicity groups. No ToxN=138 MNTN=8 CNPN=12 IEC-ECN=6 p value Peak ALC (10 9 /L), median (IQR) 1.8 (1.0-4.1) 6.2 (4.8-14.4) 4.3 (3.2-6.7) 3.6 (1.9-5.2) <0.001 1 ALC >3 x 10 9 /L, n (%) 43 (31%) 7 (88%) 10 (83%) 4 (67%) <0.001 2 Odd Ratios vs no Tox 3 , 95% CI 15.5 (2.6-293.7) 11.0 (2.8-73.9) 4.4 (0.8-25.0) 1 Wilcoxon/Kruskal-Wallis Tests, 2 Chi square test, 3 Logistic regression analysis.

e15003 Background: Antibody-drug conjugates (ADCs) have shown substantial promise as therapies for metastatic breast cancer (mBC). However, direct comparisons of different ADC-based regimens are limited. We assessed survival outcomes in mBC patients treated with ADCs. Methods: Randomized controlled trials (RCTs) published before October 2024 were searched in Medline, Embase, ClinicalTrials.gov, and Cochrane Library. Progression-free survival (PFS) and overall surcvival (OS) outcomes were extracted from the most updated publications. Participants were stratified based on molecular subtypes, hormone receptor (HR) status, duration of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) treatment, and sensitivity to endocrine therapy (ET). Bayesian frameworks were deployed, presenting the synthesized outcomes of indirect comparisons using the surface under the cumulative ranking curve (SUCRA), hazard ratio (HR), and 95% credible interval (Crl). This study was prospectively registered on the International Platform of Registered Systemic Reviews and Meta-analysis Protocols (INPLASY) (INPLASY2024110021). Results: A total of 6449 patients from 12 RCTs of ADCs ado-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), and datopotamab deruxtecan (Dato-DXd) were included in the analysis. Compared to chemotherapy, T-DXd significantly improved PFS (HR 0.35, 95% Crl 0.15-0.84) and OS (HR 0.56, 95% Crl 0.32-1.0). SG also significantly extended OS (HR 0.65, 95% Crl 0.43-0.97) but not PFS. In HER2+ mBC, pooled analyses revealed T-DXd was the most effective treatment in terms of PFS, with a SUCRA of 94.2%, followed by T-DM1 (58.9%), and chemotherapy with HER2-directed therapy (34.2%). Synthesized outcomes of OS mirrored the PFS outcomes. In HR+/HER2- mBC (some of which was HER2-low), Dato-DXd (76.1%) showed slightly superior efficacy over SG (67.4%) for PFS, while SG (85.1%) was advantageous over Dato-DXd (49.1%) in terms of OS. Among patients with HR+/HER2+ mBC, T-DXd (80.0%), SG (55.5%), and chemotherapy with HER2-directed therapy (53.1%) were the most effective therapies for prolonging PFS. Regarding OS, SG (70.3%) and T-DM1 (60.3%) were the most effective, with comparable efficacy observed between chemotherapy with HER2-directed therapy (52.1%) and T-DXd (52.0%). In HR-/HER2+ mBC, T-DXd (78.1%), SG (56.1%), and T-DM1 (51.5%) significantly prolonged PFS, while SG (69.4%) had the most substantial benefit for OS, followed by T-DXd (62.8%) and chemotherapy with HER2-directed therapy (57.6%). Dato-DXd showed an advantage over SG in mBC patients received CDK4/6i for > 12 months. Conclusions: This network meta-analysis showed prominent survival benefits with ADC-containing regimens for mBC. Our results provide valuable insights into personalized treatment strategies for mBC patients.

7032 Background: The impact of immune cell counts pre LD and during immune reconstitution on CAR T therapy outcomes is poorly understood. We investigated the association between CD4, CD8 and NK cell counts and CAR T therapy outcomes in patients with LBCL. Methods: Retrospective study of R/R LBCL patients who received CAR T cells between 2016-24 at Mayo Clinic, Rochester, were included in this analysis. Peripheral blood CD4, CD8 and NK counts were measured pre LD and at M1 post CAR T infusion. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff for pre LD and M1 immune cells to predict patients who were alive and in remission at 6 months (M6) post CAR T infusion. Patients who progressed or were lost to follow up prior to day 30 were excluded from M1 ROC analysis. Results: Of 140 patients, 81 were alive and in remission at M6 (Group A), while 59 had relapse or death (Group B). Axicabtagene ciloleucel was the CAR T product given in 81% of patients (114/140). Median pre LD CD4 counts were significantly lower in Group B compared to group A (143 vs 280 cells/µL, p = 0.001). No significant difference was observed in median pre LD CD8 counts (205 vs 221 cells/µL, p = 0.8). ROC analysis identified an optimal pre LD CD4 count of 124.5 cells/µL for M6 alive+remission. Lower pre LD CD4 counts (<124.5) predicted worse progression free survival (PFS) in univariate (HR = 3.02, 95% confidence interval [CI]: 1.73–5.27, p< 0.01) and multivariable analysis (MVA) adjusted for IPI and the number of prior lines (aHR = 2.54, 95% CI: 1.39–4.62, p< 0.01).Lower pre LD CD4 counts also predicted inferior overall survival (OS) in MVA (aHR = 2.27, 95% CI: 1.08–4.77, p = 0.03). (Table 1) On day 30 landmark analysis, ROC identified M1 optimal CD4 count of ≥ 99.5 cells/µL to be associated with a trend toward superior PFS (P=0.09), but not OS (p=0.90) in MVA. Median pre LD NK cell counts were significantly lower in Group B (73 vs 98 cells/µL, p = 0.04). ROC analysis identified an optimal pre LD NK count of 151 cells/µL for M6 alive + remission. Lower pre LD NK counts (<151) predicted worse PFS, both on univariate (HR = 4.17, 95% CI: 1.29–13.47, p = 0.02) and MVA (aHR = 4.64, p< 0.01). The lower pre LD NK cell count group had worse OS in MVA (aHR = 5.69, 95% CI: 1.16–28.1, p = 0.01). (Table 1) On D30 landmark analysis, M1 NK cell count of ≥ 128.5 cells/µL was associated with a trend toward superior PFS (P=0.08), but not OS (p=0.30) in MVA. Conclusions: Pre LD CD4 and NK cell counts are significantly associated with PFS and OS post CAR T therapy in patients with R/R LBCL. Pre-treatment immune subset levels may identify patients at higher risk of relapse or death after CAR-T therapy. Groups Median PFS 2 Year PFS Median OS 2 Year OS CD4 ≥124.5 cells/µL (N=75) NR 58% 3.31 years 67% CD4 <124.5 cells/µL (N=30) 2.2 months 22% 1.59 years 45% NK ≥151 cells/µL (N=17) NR 77% NR 84% NK <151 cells/µL (N=82) 10.6 months 44% 3.31 years 62%

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.

e19008 Background: Cytokine release syndrome (CRS) is typically reversible in CAR-T therapy, while hyperinflammatory syndromes like macrophage activation-like syndrome (MAS-L) and high-grade immune effector cell-associated hemophagocytic syndrome (IEC-HS) are associated with significant morbidity and mortality. Early interventions are critical for improving outcomes. We aim to analyze clinical cytokine assays and cellular phenotypes early in hyperinflammatory syndromes to identify profiles for severe cases to inform management decisions. Methods: This study included 113 CAR-T patients (pt) (September 2019-March 2024) with cytokine profiles (CP) performed at the second tocilizumab dose or with suspected hyperinflammatory states (CP1), followed by assessments at 24 hours (CP24) and 48 hours (CP48). 52 pts consented to blood (PB) and bone marrow (BM) cell immune phenotyping at pre-treatment (pre-LD) and day 1 for PB. Results: Among the 113 pts, CRS pts (N=74), when compared to MAS-L(N=19) & IEC-HS (N=20) at CP1, had lower levels of TNF (median in pg/mL; 31, 62.9, 47.7) , IL-18 (794, 1353, 2011), and MCP-1 (689, 2722, 2485.5). While MAS-L and IEC-HS had similar CP1 profiles, CP24 and CP48 differed between them: TNF & MCP-1 levels decreased in MAS-L but remained elevated or increased in IEC-HS. IL-18 was stable in MAS-L but increased steadily daily in IEC-HS. Infections were more frequent in IEC-HS (CRS: 43%; MAS-L: 58%; IEC-HS: 85%; p=0.002). Notably, patients who died with persistent E. faecium bacteremia had higher IL-18 in CP48. In the 52 pts with cell phenotypes available by flow, 33 had CRS, 18 MAS-L and 8 IEC-HS. The correlation between cell phenotypes and cytokine levels showed that elevated TNF at CP1 correlated with increased non-classical monocytes in pre-LD BM and higher NK and NK-T cells in pre-LD PB. Similarly, elevated IL-18 CP48 levels correlated with increased CD8 T-cells, NK-T cells, and intermediate monocytes in pre-LD PB, as well as increased NK cells at both pre-LD and day 1 (Table). Conclusions: We report distinct cytokine profiles in IEC-HS early in the inflammatory course post-CAR-T therapy. These elevated cytokines correlate with specific immune cell subsets, including BM-resident monocytes, intermediate monocytes with heightened cytokine trafficking and inflammatory capacity. This study demonstrates the feasibility for identifying potential biomarkers for early risk stratification and targeted interventions. Cytokine Sample source Immune cells R P value TNF CP1 BM pre-LD Non-classical monocytes (CD14loCD16+) 0.38 0.025 PB pre-LD Monocytes (All) 0.47 0.022 NK cells (CD56+CD16+) 0.34 0.024 NK-T cells (CD3+CD56+CD16-) 0.29 0.04 IL-18 CP48 PB pre-LD CD8+ T-cells 0.59 0.0093 NK-T cells (CD3+CD56+CD16-) 0.53 0.023 Intermediate monocytes (CD14+CD16+) 0.58 0.012 PB pre-LD NK cells (CD56+CD16+) 0.56 0.49 0.015 0.024

PURPOSE Cytokine release syndrome (CRS) of any grade occurs in 56%-80% of bispecific antibodies (BsAbs) used in multiple myeloma (MM). Risk mitigation strategies are required to expedite escalation of care if toxicities develop. The rarity of grade 3 or 4 CRS compels protocolized outpatient management of BsAbs as outpatient practice may avoid hospital admissions and costly resource utilization without compromising safety. MATERIALS AND METHODS Patients with MM who received BsAb step-up dosing (SUD) from August 23, 2023, to March 29, 2024, were enrolled. Baseline demographics, patient outcomes, and CRS management were reviewed to assess the safety of outpatient practice. Resource utilization was also analyzed. RESULTS In this study, 34 patients received outpatient SUD of BsAbs (teclistamab n = 17, talequetamab n = 17) with 16 remaining outpatient throughout the entire SUD period. CRS occurred in seven patients who did not require hospitalization, demonstrating the safety of outpatient management of BsAb toxicity, regardless of low-grade CRS. CRS was observed in 24 patients (maximum grade 2) and immune effector cell–associated neurotoxicity syndrome in four patients (maximum grade 3). All patients with CRS received steroids, including 12 patients at home when instructed. Tocilizumab was given to 13 patients, accounting for 18 doses. If all doses of BsAbs and tocilizumab were given outpatient, the medication margin would be $115,004 in US dollars (USD). CONCLUSION An outpatient-based practice for BsAb administration demonstrated safety and cost savings. The description of our practice and results of this study provide valuable insights into the safety, feasibility, and resource stewardship of outpatient management of BsAbs. Future research should attempt to predict and stratify CRS risk to deliver a tailored supportive strategy and continued increase of outpatient management.

PURPOSE Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), two B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). We compare safety, efficacy, and survival among patients with RRMM treated with standard-of-care (SOC) ide-cel or cilta-cel. METHODS Data were from a retrospective chart review of patients with RRMM leukapheresed by December 31, 2022, with the intent to receive SOC ide-cel or cilta-cel at 19 institutions. An inverse probability of treatment weighting (IPTW) approach was used to compare outcomes by therapy type. RESULTS A total of 641 patients were leukapheresed by December 31, 2022, with ide-cel (n = 386) and cilta-cel (n = 255). Five hundred eighty-six patients were infused (n = 350 for ide-cel; n = 236 for cilta-cel) with a median follow-up of 12.6 and 13.0 months for ide-cel and cilta-cel, respectively. After IPTW, patient characteristics were well balanced. Cilta-cel was associated with higher likelihood of grade ≥3 cytokine release syndrome (CRS; odds ratio [OR], 6.80 [95% CI, 2.28 to 20.33]), infections (OR, 2.03 [95% CI, 1.41 to 2.92]), second primary malignancies (OR, 1.77 [95% CI, 0.89 to 3.56]), and delayed neurotoxicity (OR, 20.07 [95% CI, 4.46 to 90.20]). Cilta-cel was also associated with better treatment responses (≥complete response: OR, 2.42 [95% CI, 1.63 to 3.60]), longer progression-free survival (hazard ratio [HR], 0.48 [95% CI, 0.36 to 0.63]), and longer overall survival (HR, 0.67 [95% CI, 0.46 to 0.97]). No associations were observed between therapy type and immune effector cell–associated neurotoxicity syndrome, any CRS, severe cytopenia at days 30 and 90, or nonrelapse mortality. We observed consistent findings when repeating the analyses restricting the ide-cel cohort to patients infused during the same time period as Food and Drug Administration approval for cilta-cel (≥March 2022). CONCLUSION Cilta-cel demonstrated superior efficacy and survival, with higher incidence of certain toxicities, compared with ide-cel.