Introduction
B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment landscape of multiple myeloma [ 1 – 3 ]. In February 2022, the United States (US) Food and Drug Administration (FDA) approved ciltacabtagene autoleucel (cilta-cel), an anti-BCMA CAR-T with 2 identical camelid-derived heavy-chain antibodies on each chimeric receptor, for patients who have received ≥4 prior lines of therapy with subsequent updated earlier line approval in April 2024 [ 4 – 8 ]. Cilta-cel approval was based on the Phase Ib/II CARTITUDE-1 clinical trial demonstrating an overall response rate (ORR) of 98% and complete response or better (≥CR) of 83%. Median progression-free survival (PFS) was 34.9 months, and overall survival (OS) was 60.7 months [ 6 , 8 ]. In terms of safety, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 95% and 17% of patients, respectively. Non-ICANS neurotoxicity (NINT), including Parkinsonism and cranial nerve palsies, occurred in 12% of patients [ 4 – 8 ].
Clinical trials have stringent eligibility criteria, which lead to the inclusion of patients with limited comorbidities and may not be reflective of routine clinical practice [ 9 – 14 ]. Utilizing the Center for International Blood and Marrow Transplant Research (CIBMTR) infrastructure and registry, we aimed to investigate the safety and efficacy of cilta-cel in a real-world patient population overall and in high-risk patient subgroups. We hypothesized that in standard-of-care (SOC), cilta-cel would demonstrate safety and efficacy profile similar to that of CARTITUDE-1.
Methods
Data source
CIBMTR is a research collaboration between the National Marrow Donor Program (NMDP) and the Medical College of Wisconsin. More than 375 medical centers worldwide submit clinical data to CIBMTR about hematopoietic cell transplant, CAR T-cell therapy, and other cellular therapies for treatment of malignancies. CIBMTR data undergoes a series of automated and manual quality checks to maximize its validity. In addition, CIBMTR audits each contributing center periodically. CIBMTR protects the privacy and human rights of participants and obeys international laws and ethical guidelines. The NMDP Institutional Board reviews CIBMTR research. Patients or guardians give informed consent to share data for research.
Patients
All patients with relapsed/refractory multiple myeloma (RRMM) who received SOC cilta-cel after ≥4 prior lines of therapy from March 2022 to December 2023, and with at least a 100-day post CAR-T evaluation, were eligible for study inclusion. Patients receiving CAR-T who did not meet FDA release criteria for an in-specification product were excluded. High-risk cytogenetics was defined by the presence of t (4;14), t (14;16), t (14:20) and/or deletion 17p at any time before CAR-T infusion. Extramedullary disease (EMD) was reported as present if noted organ involvement as assessed by imaging (computed tomography, magnetic resonance or positron emission tomography) before CAR-T infusion as defined by each center, and may include both true extramedullary and paramedullary disease due to limitations in registry-level classification [ 15 ]. As part of the study was conducted during a U.S. fludarabine shortage, alternative lymphodepletion (LD) regimens were given at each center’s discretion to include bendamustine and cyclophosphamide.
Outcomes
The primary outcomes were efficacy, defined as ORR and PFS from CAR-T infusion. Secondary endpoints included OS and other safety measures such as CRS, ICANS, non-ICANS NT, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), cytopenias, infections, second primary malignancies (SPM), and treatment-related mortality (TRM). CRS and ICANS were assessed per the American Society of Transplantation and Cellular Therapy consensus criteria [ 16 ], whereas myeloma responses were assessed per International Myeloma Working Group criteria [ 17 ]. Non-ICANS NT was defined based on the reporting of specific neurologic symptom patterns consistent with delayed or atypical neurotoxicity in the CIBMTR registry. Detailed longitudinal neurologic characterization and precise adjudication of onset timing were limited by the structure of the CIBMTR forms. Neutrophil recovery was defined as achieving a neutrophil count of >500/µL for 3 consecutive days with the first day counted as the day of recovery, while platelet recovery was defined as a platelet count of >20,000/µL without platelet transfusion within the last 7 days of the follow-up visit. Prolonged cytopenias were defined as absence of neutrophil and/or platelet recovery by 30 days following cilta-cel infusion. In line with CIBMTR definitions, infections were considered clinically significant if they required treatment. Episodes of neutropenic fever without an identifiable source and upper respiratory tract infections presumed viral but lacking pathogen confirmation were excluded. TRM was defined as death in the absence of disease progression.
Statistical analysis
Distribution of patient characteristics were examined using chi-square or Fisher’s exact tests for categorical variables or Wilcoxon rank-sum test/Kruskal–Wallis test for continuous variables. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Multivariable regression models were performed for the following outcomes: ≥grade 2 CRS, any grade ICANS, best ORR, ≥CR, PFS, and OS. A stepwise variable selection approach with a significance threshold of P < 0.05 was used to identify covariates for inclusion in the final models. Logistic regression was used for binary outcomes (≥grade 2 CRS, any grade ICANS, best ORR, ≥CR), whereas Cox proportional hazard models were applied for time-to-event endpoints (PFS, OS). The proportional hazards assumption and potential cross-variable interactions were tested on all models. Hazard ratios (HR) or odds ratios (OR) with 95% CI were estimated and reported for all models. Variables included in the models were (1) age category (<60, 60–69, and ≥70); (2) sex; (3) race (White, Black or African-American, others, not reported); (4) Eastern Cooperative Oncology Group performance score at infusion (ECOG 0-1, ECOG ≥ 2, missing); (5) number of prior lines of therapy (4–6, 7–10, >10); (6) International Staging System (ISS) stage at diagnosis (I, II, III, and unknown); (7) marrow plasma cell burden before infusion (<50%, ≥50%, unknown); (8) lactate dehydrogenase (LDH) before infusion (normal, elevated, unknown); (9) baseline ferritin (≥150 ng/mL vs <150 ng/mL); (10) presence of EMD; (11) prior BCMA-directed therapy; (12) disease status at infusion (≥very good partial response [VGPR], PR, stable disease, progressive disease, and unknown status); (13) type of lymphodepleting chemotherapy (fludarabine and cyclophosphamide vs bendamustine); (14) absolute neutrophil count before cilta-cel infusion (≥750/µL vs. <750/µL); (15) hemoglobin before cilta-cel infusion (≥8 g/dL vs <8 g/dL); (16) platelet count before cilta-cel infusion (>50,000 vs. <50,000/µL); and (17) cilta-cel dosing (≥0.7 million cells vs. < 0.7 million cells) and (17) hematopoietic cell transplantation-specific comorbidity index.
PFS was defined as the time from cilta-cel infusion until disease progression, death from any cause, or last follow-up. OS was defined as the time from cilta-cel infusion until death from any cause or last follow-up. The Kaplan–Meier method was used to estimate overall PFS and OS, and log-rank tests were used to compare PFS and OS by selected patient characteristics. All P values were 2-sided, and the difference between 2 variables was considered significant at P < 0.05.
Ethical approval
All Center for International Blood and Marrow Transplant Research studies are reviewed and approved by the National Marrow Donor Program Institutional Review Board, and all patients (or their legal guardians) provided informed consent for data collection and research.
Results
Patient characteristics
A total of 595 RRMM patients were infused with SOC cilta-cel (Supplementary Fig. 1 ). Table 1 shows the distribution of patient characteristics. The median age was 64 years (range: 34–84) and 57% were male. Most patients were White (77%) with Black and Hispanic patients representing 15% and 9% of the cohort, respectively. Most patients had an ECOG PS of 0–1 (89%). At least 1 clinically significant comorbidity was present in 70% of patients before cilta-cel. Common comorbidities included moderate to severe cardiac disease (26%), pulmonary disease (24%), renal impairment (5%), cerebrovascular disease (4%), and history of prior malignancies (15%). Table 1 Baseline characteristics of patients who received standard-of-care ciltacabtagene autoleucel. Characteristic N (%) or median (range), N = 595 Age, years 64 years (34–84) Age ≥70 years 134 (23) Sex Male 340 (57) Ethnicity Hispanic (any race) 54 (9) Race White 456 (77) Black or African American 89 (15) Asian/Pacific Islander 20 (3) More than 1 race 4 (1) Unknown 26 ECOG PS 0–1 527 (89) 2–4 19 (3) Unknown 49 Myeloma subtype Oligo/Non-secretory 15 (3) ISS disease stage I 154/260 (59) II 66/260 (25) III 40/260 (15) Unknown 335 Cytogenetic abnormality Any high-risk cytogenetics a 142/530 (27) High-risk cytogenetics including 1q 277/530 (52) Unknown 65 High marrow burden BMPCs ≥ 50% Yes 54/373 (14) Unknown 222 Extramedullary disease Yes 50/382 (13) Unknown 213 Plasma cell leukemia (active or history) 6 (1) Prior therapies Number of prior antimyeloma therapies 7 (4–24) Prior autologous SCT 471 (79) Prior allogeneic SCT 4 (1) Prior anti-BCMA therapy 45 (8) Prior belantamab mafodotin 37 (6) Prior anti-BCMA CAR-T 3 (1) Prior bispecific antibody 7 (1) >1 BCMA targeting therapies b 1 (0.2) Triple-exposed 507 (85) Penta-exposed 328 (55) Clinically significant comorbidity 416 (70) Cardiac disease 81 (14) Arrythmia 61 (10) Heart valve disease 12 (2) Cerebrovascular disease 25 (4) Hepatic 6 (1) Pulmonary 140 (24) Renal 29 (5) Prior malignancy 91 (15) Baseline cytopenia Hemoglobin <8 g/dL 54 (9) Platelets <50,000/μL 51 (9) Absolute neutrophil count <750/μL 21 (4) Baseline inflammatory markers Ferritin ≥150 ng/mL 172/328 (52) CRP ≥ 0.5 mg/dL 158/353 (45) Bridging therapy 339 (57) Disease status prior to infusion PR or better 145 (24) SD/PD 445 (75) Unknown 5 Lymphodepletion chemotherapy Fludarabine + cyclophosphamide 461 (78) Bendamustine 111 (19) Other 22 (4) Unknown 1 CAR T-cell dose ≥ 0.7 million 172 (29) Days from leukapheresis to infusion 63 (56–71) Cytopenias were defined as hemoglobin <8 g/dL, absolute neutrophil count <750/μL and platelets <50,000/μL. Percentage totals may exceed 100% due to rounding. When 10% of more data was missing for a given variable, denominator changed to patients with data available. BCMA B-cell maturation antigen, BMPC bone marrow plasma cells, CAR T-cell therapy chimeric antigen receptor T-cell therapy, CRP C-reactive protein, ECOG PS Eastern Cooperative Oncology Group performance status, ISS international staging system, PD progressive disease, PR partial response, SCT stem cell transplantation, SD stable disease. a High-risk cytogenetics: Includes del(17p), t(4;14) and t(14;16). High marrow burden was defined as > 50% plasma cells before CAR-T infusion; Penta-exposed disease: exposed to lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab or isatuximab. Triple-exposed disease: exposed to an IMiD, PI, and an anti-CD38 monoclonal antibody. b Patient who received bispecific antibody and belantamab.
Table 1
Baseline characteristics of patients who received standard-of-care ciltacabtagene autoleucel.
Cytopenias were defined as hemoglobin <8 g/dL, absolute neutrophil count <750/μL and platelets <50,000/μL. Percentage totals may exceed 100% due to rounding. When 10% of more data was missing for a given variable, denominator changed to patients with data available. BCMA B-cell maturation antigen, BMPC bone marrow plasma cells, CAR T-cell therapy chimeric antigen receptor T-cell therapy, CRP C-reactive protein, ECOG PS Eastern Cooperative Oncology Group performance status, ISS international staging system, PD progressive disease, PR partial response, SCT stem cell transplantation, SD stable disease. a High-risk cytogenetics: Includes del(17p), t(4;14) and t(14;16). High marrow burden was defined as > 50% plasma cells before CAR-T infusion; Penta-exposed disease: exposed to lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab or isatuximab. Triple-exposed disease: exposed to an IMiD, PI, and an anti-CD38 monoclonal antibody. b Patient who received bispecific antibody and belantamab.
| Characteristic | N (%) or median (range), N = 595 |
| Age, years | 64 years (34–84) |
| Age ≥70 years | 134 (23) |
| Sex | |
| Male | 340 (57) |
| Ethnicity | |
| Hispanic (any race) | 54 (9) |
| Race | |
| White | 456 (77) |
| Black or African American | 89 (15) |
| Asian/Pacific Islander | 20 (3) |
| More than 1 race | 4 (1) |
| Unknown | 26 |
| ECOG PS | |
| 0–1 | 527 (89) |
| 2–4 | 19 (3) |
| Unknown | 49 |
| Myeloma subtype | |
| Oligo/Non-secretory | 15 (3) |
| ISS disease stage | |
| I | 154/260 (59) |
| II | 66/260 (25) |
| III | 40/260 (15) |
| Unknown | 335 |
| Cytogenetic abnormality | |
| Any high-risk cytogenetics a | 142/530 (27) |
| High-risk cytogenetics including 1q | 277/530 (52) |
| Unknown | 65 |
| High marrow burden BMPCs ≥ 50% | |
| Yes | 54/373 (14) |
| Unknown | 222 |
| Extramedullary disease | |
| Yes | 50/382 (13) |
| Unknown | 213 |
| Plasma cell leukemia (active or history) | 6 (1) |
| Prior therapies | |
| Number of prior antimyeloma therapies | 7 (4–24) |
| Prior autologous SCT | 471 (79) |
| Prior allogeneic SCT | 4 (1) |
| Prior anti-BCMA therapy | 45 (8) |
| Prior belantamab mafodotin | 37 (6) |
| Prior anti-BCMA CAR-T | 3 (1) |
| Prior bispecific antibody | 7 (1) |
| >1 BCMA targeting therapies b | 1 (0.2) |
| Triple-exposed | 507 (85) |
| Penta-exposed | 328 (55) |
| Clinically significant comorbidity | 416 (70) |
| Cardiac disease | 81 (14) |
| Arrythmia | 61 (10) |
| Heart valve disease | 12 (2) |
| Cerebrovascular disease | 25 (4) |
| Hepatic | 6 (1) |
| Pulmonary | 140 (24) |
| Renal | 29 (5) |
| Prior malignancy | 91 (15) |
| Baseline cytopenia | |
| Hemoglobin <8 g/dL | 54 (9) |
| Platelets <50,000/μL | 51 (9) |
| Absolute neutrophil count <750/μL | 21 (4) |
| Baseline inflammatory markers | |
| Ferritin ≥150 ng/mL | 172/328 (52) |
| CRP ≥ 0.5 mg/dL | 158/353 (45) |
| Bridging therapy | 339 (57) |
| Disease status prior to infusion | |
| PR or better | 145 (24) |
| SD/PD | 445 (75) |
| Unknown | 5 |
| Lymphodepletion chemotherapy | |
| Fludarabine + cyclophosphamide | 461 (78) |
| Bendamustine | 111 (19) |
| Other | 22 (4) |
| Unknown | 1 |
| CAR T-cell dose ≥ 0.7 million | 172 (29) |
| Days from leukapheresis to infusion | 63 (56–71) |
The median number of prior lines of therapy was 7 (range: 4–24), 85% of patients were triple-class exposed, and 55% were penta-drug exposed. High-risk cytogenetics was present in 27%, with advanced stage ISS II–III, EMD, and high tumor burden (≥50% bone marrow plasma cells) observed in 40%, 13%, and 14% of patients, respectively. Notably, 8% of patients had received prior BCMA-directed therapy, consisting of an antibody drug conjugate (ADC), belantamab mafodotin (6%, n = 37), prior CAR-T 0.5%, n = 3), bispecific antibody (teclistamab, 1%, n = 7), and more than 1 prior BCMA therapy in 1 patient who received both teclistamab and belantamab mafodotin (Supplementary Table 1 ).
Overall, 5 patients had received prior CAR-T, primarily through investigational trials, including bb21217 ( n = 1), a CD28-based anti-BCMA CAR-T ( n = 1), an unknown anti-BCMA CAR-T ( n = 1), a clustered regularly interspaced short palindromic repeats–(CRISPR)-edited allogeneic anti-BCMA CAR-T ( n = 1), and anti–G protein–coupled receptor, class C, group 5, member D (GPRC5D) CAR-T ( n = 1). Bridging therapy was administered in 57% of patients (Supplementary Table 2 ), and 24% achieved a disease status of ≥ partial response (PR) prior to infusion. Lymphodepletion chemotherapy consisted of fludarabine and cyclophosphamide in 78%, bendamustine in 19% during the era of fludarabine shortage in the U.S., and other regimens in 4%. The median follow-up for this cohort was 12 months (range, 1.1–25.4 months).
Safety
Any grade, grade ≥2, and grade ≥3 CRS occurred in 80%, 20%, and 4% of patients, respectively (Table 2 ). Any grade, grade ≥2, and grade ≥3 ICANS occurred in 22%, 8%, and 4% of patients, respectively. Median time to onset of CRS was 8 days with 4 grade 5 events observed. Median time to onset of ICANS was 9 days with 2 grade 5 events observed. On multivariable analysis, high tumor burden (≥50% bone marrow plasma cells) was associated with higher likelihood of developing grade ≥2 CRS (OR 3.80, 95% CI: 2.05–7.03; Supplementary Table 3 ). On multivariable analysis, older age ≥70 years (OR 1.98, 95% CI: 1.17–3.37), high plasma cell burden (OR 2.60, 95% CI: 1.35–5.02), hemoglobin <8 g/dL (OR 2.54, 95% CI: 1.37–4.73), and hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥ 2 (OR 1.81, 95% CI: 1.20–2.74) were associated with higher risk of developing any grade ICANS (Supplementary Table 4 ). Non-ICANS neurotoxicity (NINT) was observed in 5% ( n = 31; Supplementary Table 5 ). Sixteen patients (2.7%) developed Parkinsonism and 15 patients (2.5%) experienced motor neuron disorders, all of which were cranial nerve palsies, most commonly involving cranial nerve VII (12/15). Median time to onset of Parkinsonism was 10 days (range: 8–21) while median time to onset of cranial nerve palsy was 20 days (range: 17–31). Multivariable analysis for NINT was not performed due to small number of events. Table 2 Safety outcomes in patients who received standard-of-care ciltacabtagene autoleucel. Event N (%) or median (range) CRS Any grade; grade ≥3 475 (80); 26 (4) Grade 1 355 (60) Grade 2 91 (15) Grade 3 13 (2) Grade 4 9 (2) Grade 5 4 (1) Unknown 3 Median time to onset from CAR-T therapy, days 8 (6–9) Median duration, days 4 (3–5) ICANS Any grade; grade ≥3 133 (22); 26 (4) Grade 1 60 (10) Grade 2 20 (3) Grade 3 17 (3) Grade 4 7 (1) Grade 5 2 Unknown 47 Median time to onset from CAR-T therapy, days 9 (6–12) Median duration, days 5 (2–10) NINT Any 31 (5) Parkinsonism 16 (2.7) Cranial nerve palsies 15 (2.5) IEC-HS 21 (4) Clinically significant infection 281 (47) Bacterial 116 (20) Viral 194 (33) Fungal 14 (2) Other, more than 1 pathogen type 69 (12) Cytopenias at day 30 145 (24) Prolonged thrombocytopenia 107 (18) Prolonged neutropenia 89 (15) Treatment-related mortality (TRM) 27 (5) Second primary malignancies (SPM) 27 (5) SPM excluding non-melanoma skin cancers 18 (3) Myeloid neoplasms/acute leukemia, myelodysplastic syndrome, T-cell lymphoma 7 (1) Prolonged cytopenias: defined as nonrecovery of counts by day 30 to the following thresholds among alive patients. Neutrophil recovery: defined as achieving a neutrophil count of >500/µL for 3 consecutive days and the first day is the recovery day. Platelet recovery: defined as platelets 20,000/µL without platelet transfusion in the last 7 days. CAR chimeric antigen receptor, CRS cytokine release syndrome, ICANS immune effector cell–associated neurotoxicity, IEC-HS immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome, NINT non-ICANS neurotoxicity, SPM second primary malignancies, TRM treatment-related mortality.
Table 2
Safety outcomes in patients who received standard-of-care ciltacabtagene autoleucel.
Prolonged cytopenias: defined as nonrecovery of counts by day 30 to the following thresholds among alive patients. Neutrophil recovery: defined as achieving a neutrophil count of >500/µL for 3 consecutive days and the first day is the recovery day. Platelet recovery: defined as platelets 20,000/µL without platelet transfusion in the last 7 days. CAR chimeric antigen receptor, CRS cytokine release syndrome, ICANS immune effector cell–associated neurotoxicity, IEC-HS immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome, NINT non-ICANS neurotoxicity, SPM second primary malignancies, TRM treatment-related mortality.
| Event | N (%) or median (range) |
| CRS | |
| Any grade; grade ≥3 | 475 (80); 26 (4) |
| Grade 1 | 355 (60) |
| Grade 2 | 91 (15) |
| Grade 3 | 13 (2) |
| Grade 4 | 9 (2) |
| Grade 5 | 4 (1) |
| Unknown | 3 |
| Median time to onset from CAR-T therapy, days | 8 (6–9) |
| Median duration, days | 4 (3–5) |
| ICANS | |
| Any grade; grade ≥3 | 133 (22); 26 (4) |
| Grade 1 | 60 (10) |
| Grade 2 | 20 (3) |
| Grade 3 | 17 (3) |
| Grade 4 | 7 (1) |
| Grade 5 | 2 |
| Unknown | 47 |
| Median time to onset from CAR-T therapy, days | 9 (6–12) |
| Median duration, days | 5 (2–10) |
| NINT | |
| Any | 31 (5) |
| Parkinsonism | 16 (2.7) |
| Cranial nerve palsies | 15 (2.5) |
| IEC-HS | 21 (4) |
| Clinically significant infection | 281 (47) |
| Bacterial | 116 (20) |
| Viral | 194 (33) |
| Fungal | 14 (2) |
| Other, more than 1 pathogen type | 69 (12) |
| Cytopenias at day 30 | 145 (24) |
| Prolonged thrombocytopenia | 107 (18) |
| Prolonged neutropenia | 89 (15) |
| Treatment-related mortality (TRM) | 27 (5) |
| Second primary malignancies (SPM) | 27 (5) |
| SPM excluding non-melanoma skin cancers | 18 (3) |
| Myeloid neoplasms/acute leukemia, myelodysplastic syndrome, T-cell lymphoma | 7 (1) |
IEC-HS occurred in 4% while clinically significant infections occurred in 47% of patients post CAR-T. Infections were mostly bacterial (20%) or viral (33%), while fungal infections (2%) were less common. Prolonged cytopenias were observed in 24% with neutropenia and thrombocytopenia seen in 15% and 18% of patients at day 30, respectively. SPM occurred in 5%, consisting primarily of nonmelanoma skin cancers. Hematologic malignancies (myelodysplastic syndrome and non-Hodgkin’s lymphoma) occurred in 1%, with no observed malignancies of T-cell origin (Supplementary Table 5 ).
Ninety-one patients (15%) who received cilta-cel have died by last follow-up: 53 deaths (9%) were attributed to myeloma progression, 27 (5%) were a result of TRM, and death cause was unknown in 11 patients. The cumulative incidence of TRM at 12-months was 5% (95% CI, 3–7). The most common cause of TRM was infection ( n = 11, including COVID-19, n = 1). Other causes of TRM included organ failure ( n = 8), CRS ( n = 4), ICANS ( n = 2), intracranial hemorrhage and other central nervous system pathology ( n = 2), and SPM ( n = 2, myelodysplastic syndrome). Two patients had overlapping attribution to CRS and organ failure. No deaths secondary to NINT were observed.
Response to therapy
The best ORR was 87%, VGPR or better rate was 75%, and CR or better rate was 35% (Fig. 1A ). The ORR and CR rates in clinically relevant patient subgroups were as follows: patient age ≥70 years (85% and 34%), ECOG ≥ 2 (74% and 32%), high-risk cytogenetics (88% and 31%), EMD (77% and 40%), ISS stage III (85% and 26%), prior BCMA-directed therapy (70% and 17%), and bendamustine LD regimen (80% and 22%), respectively (Supplementary Table 6 ). On multivariable analysis, bendamustine LD (OR 0.50, 95% CI: 0.32–0.78, P = 0.0025) and Black or African American race (versus white; OR 0.58, 95% CI: 0.37–0.92, p = 0.0192) were associated with inferior rates of CR (Supplementary Table 7 ). Fig. 1 Efficacy with ciltacabtagene autoleucel. A Overall response rates by time. B Progression-free survival. C Overall survival. ORR overall response rate, VGPR very good partial response, CR/sCR complete or stringent complete response, OS overall survivaL, PFS progression-free survival.
Survival
Median PFS and OS for the entire cohort ( N = 595) were not reached. Twelve-month PFS for the entire cohort was 73% (95% CI: 68–77) and 12-month OS was 85% (95% CI: 81–88; Fig. 1B, C ). On subgroup analyses (Figs. 2A–F and 3A–F ), patients with EMD had a 12-month PFS of 58% compared to 72% in patients without EMD ( P = 0.08) and a 12-month OS of 81% vs 85% ( P = 0.60). Patients with high-risk cytogenetics had a 12-month PFS of 63% compared to 76% in patients with standard-risk cytogenetics ( P = 0.09) and a 12-month OS of 84% vs 84% ( P = 0.91). The 12-month PFS in patients who had received any prior BCMA therapy (n = 45) was 51% compared to 74% in those without prior BCMA exposure ( P < 0.001). The 12-month OS was 81% vs 85%, respectively ( P = 0.09). No significant differences in PFS (12-month PFS: 73% vs 66% vs 83%, P = 0.22) and OS (12-month OS: 84% vs 81% vs 100%, P = 0.13) were observed between patients who received fludarabine and cyclophosphamide versus bendamustine versus other LD chemotherapy during the fludarabine shortage in the U.S. The 12-month PFS in patients with ISS stage III disease was 50% compared to 58% and 79% in those with Stage II and Stage I disease, respectively ( P < 0.001). Similarly, 12-month OS was 74%, 77%, and 90% in these groups, respectively ( P < 0.001). Fig. 2 Progression-free survival outcomes with ciltacabtagene autoleucel in patient subgroups. A PFS in patients <70 years vs ≥70 years old. B PFS in patients with an ECOG PS < 2 vs ≥2. C PFS in patients with high-risk vs standard risk cytogenetics. D PFS in patients with versus without extramedullary disease. E PFS in patients with or without prior BCMA-directed therapy. F PFS in patients based on fludarabine and cyclophosphamide vs alternative lymphodepletion regimens. BCMA B-cell maturation antigen, ECOG PS Eastern Cooperative Oncology Group performance status, EMD extramedullary disease, LD lymphodepletion, PFS progression-free survival. Fig. 3 Overall survival outcomes with ciltacabtagene autoleucel in patient subgroups. A OS in patients <70 years vs ≥70 years old. B OS in patients with an ECOG PS < 2 vs ≥2. C OS in patients with high-risk vs standard risk cytogenetics. D OS in patients with versus without extramedullary disease. E OS in patients with or without prior BCMA-directed therapy. F OS in patients based on fludarabine and cyclophosphamide vs alternative lymphodepletion regimens. BCMA B-cell maturation antigen, ECOG Eastern Cooperative Oncology Group performance status, EMD extramedullary disease, LD lymphodepletion, OS overall survival.
When evaluating each type of prior BCMA-directed therapy, inferior PFS was observed in patients who received prior belantamab mafodotin and teclistamab. Twelve-month PFS in patients with prior belantamab mafodotin and teclistamab were 50% and 54%, respectively, P < 0.001. Twelve-month OS estimates for each of these subgroups were 80% and 86%, respectively, P < 0.0001. We also studied the impact of disease status prior to CAR-T infusion. Twelve-month PFS for patients in ≥VGPR vs PR vs SD/PD prior to infusion was 75%, 76%, and 72%, respectively ( P = 0.39), and the 12-month OS was 91%, 89%, and 83%, respectively ( P = 0.17; Supplementary Fig. 2 ).
Multivariable analysis identified characteristics associated with inferior PFS and these included male sex, high-risk cytogenetics, prior BCMA-directed therapy, high plasma cell burden, ECOG PS ≥ 2, elevated baseline LDH, and elevated baseline ferritin ≥150 ng/mL (Fig. 4A ). Adverse prognostic factors for OS on multivariable analysis included male sex, ECOG PS ≥ 2, elevated baseline LDH, high plasma cell burden, elevated baseline ferritin ≥150 ng/mL, and platelet count <50,000/uL before cilta-cel infusion (Fig. 4B ). Fig. 4 Multivariable Analysis of Progression-Free Survival and Overall Survival in Patients Treated with Ciltacabtagene Autoleucel. Multivariable analyses for A progression-free survival and B overall survival following ciltacabtagene autoleucel. BCMA B-cell maturation antigen, ECOG PS Eastern Cooperative Oncology Group performance status, BM bone marrow, LDH lactate dehydrogenase, OS overall survival, PFS progression-free survival.
Discussion
To our knowledge, this is the largest study to date reporting real-world outcomes of commercial cilta-cel for RRMM, including 595 patients with a median follow-up of 12 months from infusion. We observed favorable efficacy and safety, despite 70% of patients having clinically significant comorbidities that may have excluded them from CARTITUDE-1 trial participation. Our population was heavily pretreated, with a median of 7 prior lines of therapy, and 8% had previously received BCMA-directed therapy. Despite these high-risk features, SOC cilta-cel achieved favorable outcomes, with an ORR of 87% and 12-month PFS and OS rates of 73% and 85%, respectively. These results are somewhat inferior to those of CARTITUDE-1 (ORR 98%, 12-month PFS 77%, OS 89%), most likely reflecting the high prevalence of clinically significant comorbidities and prior treatment exposures in our population that may have rendered them ineligible for the trial [ 4 – 8 ]. Nevertheless, our findings are consistent with previously published real-world data (ORR 89%, CR rate 35%, 12-month PFS 68%, OS 82%) [ 11 ]. It should also be noted that CIBMTR data reporting requires strict adherence to IMWG guidelines and as a result, patients without urine immunofixation confirmation of a complete response would not be classified as such.
Given the large size of our cohort, we were able to conduct robust multivariable analyses to identify predictors of efficacy and survival. Consistent with prior reports, prior BCMA-directed therapy was associated with inferior PFS [ 18 – 22 ]. In our cohort, most patients with prior BCMA exposure had received the ADC belantamab mafodotin, whereas use of bispecific antibodies or CAR-T therapy was uncommon. With the expanding array of BCMA and GPRC5D-directed immunotherapies for RRMM, data to guide treatment selection and sequencing are urgently needed. Prior BCMA exposure has also been associated with lower response rates and PFS following ide-cel [ 10 , 12 , 22 , 23 ]. Moreover, a shorter interval from the most recent BCMA-directed therapy has been linked to inferior outcomes, not only in patients receiving commercial CAR-T therapy but also in those treated with anti-BCMA bispecific antibodies [ 20 , 22 , 24 ]. Sequencing novel immunotherapies therefore, remains an area of ongoing clinical investigation and critical importance. Looking forward, integration of molecular biomarkers and genomic prediction models may enable more personalized sequencing strategies, optimizing the use of multiple BCMA- and GPRC5D-directed agents in RRMM [ 25 , 26 ].
Apart from prior BCMA exposure, poor performance status, high marrow plasma cell burden, and elevated inflammatory markers were independently associated with inferior PFS and OS, consistent with published data on CAR-T therapy and other novel immunotherapies in RRMM [ 11 , 27 – 29 ]. High-risk cytogenetics were also linked to inferior PFS but not OS. Another important finding from our study is the prognostic impact of disease status at the time of cilta-cel infusion. Patients achieving VGPR or better at infusion had numerically superior OS compared with those in PR or SD/PD, consistent with results from the KarMMa-3 trial of ide-cel, the CARTITUDE-4 trial of cilta-cel, and other real-world data [ 7 , 11 , 30 ]. Across studies, lower disease burden at infusion has consistently correlated with improved efficacy and safety outcomes, including incidence of NINT [ 31 – 35 ].
Due to a national shortage of fludarabine, many tertiary centers adopted alternative LD regimens, most commonly bendamustine. In our cohort, bendamustine was independently associated with a lower rate of CR or better, as well as a non-statistically inferior PFS and OS compared to fludarabine and cyclophosphamide LD. Prior reports on bendamustine as LD for BCMA CAR-T have been conflicting [ 36 ]. A real-world analysis of cilta-cel demonstrated inferior PFS with bendamustine LD compared with fludarabine and cyclophosphamide (3.9 vs 9.1 months) [ 11 ]. Collectively, the available data support fludarabine and cyclophosphamide as the preferred LD regimen prior to CAR-T infusion. Residual confounding may partly account for the poorer outcomes observed with bendamustine, along with potential adverse effects on T-cell fitness and the cytokine milieu required for optimal CAR-T expansion and persistence [ 37 ].
Despite a substantial proportion of patients presenting with clinically significant comorbidities, baseline cytopenias, and older age, the safety profile of cilta-cel in our cohort was comparable to that reported in the CARTITUDE-1 trial and in prior real-world studies [ 4 , 11 ]. Grade ≥ 3 CRS and ICANS occurred in 4% of patients, respectively, with these high-grade events more frequently observed in those with high disease burden. The large size of our cohort enabled a multivariable analysis to identify risk factors for grade ≥ 2 CRS and any-grade ICANS with cilta-cel. High marrow plasma cell burden was independently associated with increased risk of both grade ≥ 2 CRS and any-grade ICANS. In addition, older age (≥ 70 years), hemoglobin <8 g/dL, and HCT-CI ≥ 2 were associated with a higher risk of any-grade ICANS. As CAR-T therapy increasingly transitions to outpatient administration, identification of such risk factors may aid in stratifying patients who would benefit from inpatient infusion, intensified bridging chemotherapy, aggressive supportive care management, and prophylactic interventions to mitigate immune-mediated toxicities. Clinically significant infections were observed in 47% of patients, consistent with prior real-world reports (46%) [ 11 ]. Most infections were bacterial or viral, as anticipated. Although antimicrobial use was not systematically captured in this registry, and detailed data on intravenous immunoglobulin use was not available compared with CARTITUDE-1, where grades 3 and 4 infections were reported in 20% of patients [ 4 ], our findings highlight the clinical importance of intensified antimicrobial prophylaxis and intravenous immunoglobulin support to reduce infection-related morbidity and mortality.
Cilta-cel has been associated with a spectrum of NINT, including nerve palsies and Parkinsonism, some of which may be irreversible and contribute to morbidity and mortality [ 4 ]. In our cohort, NINT occurred in 5% of patients, comprising a 2.7% incidence of Parkinsonism and a 2.5% incidence of motor neuron disorders, predominantly seventh cranial nerve palsies. The rates of Parkinsonism and motor neuron disorders were numerically lower in our cohort compared with the CARTITUDE trials (Parkinsonism: 2.7% vs. 5%; motor neuron disorders: 2.5% vs. 10%, including both peripheral neuropathy and cranial nerve palsies) [ 4 , 7 , 38 ]. However, the incidence of Parkinsonism was comparable to that reported in other real-world cilta-cel studies [ 11 ]. The most recent CARTITUDE-4 study [ 7 ], in which cilta-cel was administered in earlier lines of therapy, reported an even lower incidence of Parkinsonism at 1%. Due to the low frequency of these events in our cohort, we were unable to identify predictors of NINT. The biological underpinnings of these toxicities remain poorly understood.
In CARTITUDE trials, patients who developed cranial nerve palsies demonstrated higher CAR T-cell expansion, suggesting that interventions aimed at reducing CAR T-cell burden, such as high-dose corticosteroids or cytotoxic chemotherapy, may be considered [ 39 ]. Most patients with nerve palsies gradually improve and eventually recover with corticosteroids in combination with intravenous immunoglobulin, although recovery often requires several weeks to months [ 40 ]. In contrast, standard therapies for Parkinson’s disease have been ineffective in managing CAR T–related Parkinsonism. Some case reports and case series have described symptomatic improvement or resolution with intrathecal chemotherapy or regimens combining cyclophosphamide and corticosteroids [ 41 – 43 ]. Most recently, early mitigation strategies have been adopted in clinical practice, including prophylactic dexamethasone or cyclophosphamide administered at the time of peak absolute lymphocyte count (ALC) expansion (typically between days 10 and 14 post–CAR-T) in patients with elevated ALC, with the goal of reducing the risk of NINT [ 44 ]. Emerging single-center experiences have suggested limited utility of dexamethasone prophylaxis in reducing lymphocyte expansion or the incidence of NINT, underscoring the need for further prospective, methodologically robust evaluation and exploration of novel mitigation strategies [ 45 , 46 ]. However, evidence remains limited, and the optimal intervention, timing, ALC threshold, and potential impact on CAR-T efficacy are not yet established.
More recently, the risk of SPM following CAR-T in MM has gained increasing attention [ 47 – 51 ]. The first confirmed case of a T-cell lymphoma caused by CAR insertion into the TP53 gene during commercial cilta-cel manufacturing was reported by Perica et al. [ 52 ]. In our cohort, hematologic SPM occurred in 1% of patients, with no T-cell–derived malignancies observed. However, longer follow-up is required to fully characterize the long-term risk of SPM associated with cilta-cel. We observed a TRM rate of 5%, with an additional 2% of deaths due to unknown causes. This is somewhat lower than the 10% nonrelapse mortality (NRM) reported in the U.S. Multiple Myeloma Immunotherapy Consortium experience and comparable to the 6% NRM observed in CARTITUDE-1 [ 4 , 11 ]. Infections were the leading cause of death across cohorts, highlighting the need for vigilant monitoring and potentially intensifying prophylactic strategies [ 53 , 54 ].
The main strengths of our study include, to our knowledge, the largest reported cohort of patients treated with commercial cilta-cel to date. Importantly, we included patients who are typically underrepresented in clinical trials, and the large sample size allowed us to robustly assess and identify predictors of safety and efficacy. These findings not only validate but also extend previously published SOC data. Furthermore, the median follow-up of 1 year allowed us to capture short- and intermediate-term outcomes, although longer follow-up is needed to assess long-term toxicities. The size of our cohort also enabled identification of subgroups with favorable CAR-T outcomes, as well as those with inferior outcomes who may benefit from future consolidative or maintenance therapies after cilta-cel.
Our study has several limitations. Refractoriness to prior therapy after initial response is not captured in CIBMTR forms, limiting our ability to report the proportion of patients who were triple-class refractory or penta-refractory. Information on manufacturing failures and patients who did not receive cilta-cel after apheresis for other reasons is also unavailable. Additionally, measurable residual disease (MRD) status was largely unavailable, preventing MRD-based outcome analyses. Additional limitations include the relatively short follow-up, which may underestimate the incidence of late complications beyond 1 year, particularly SPM and the possibility of under-reporting of NINT. In addition, detailed longitudinal neurologic characterization and progression of neurologic symptoms attributable to NINT could not be reliably assessed within the CIBMTR registry. Other emerging AEs of cilta-cel, most notably immune effector cell-associated enterocolitis (IEC-EC), were not queried of centers in our analysis. Finally, cilta-cel is now available for use in earlier lines of therapy, which may result in better outcomes in future analyses as compared to CARTITUDE-1 or the present study (in which all patients had received at least 4 prior lines of therapy). Despite these limitations, our study provides valuable insights into cilta-cel applicability and outcomes in routine clinical practice.
In conclusion, commercial cilta-cel demonstrated a favorable safety and efficacy profile, leading to deep and durable responses. These outcomes were observed despite most patients having clinically significant comorbidities and extensive prior myeloma therapy, including BCMA-directed treatments. Close monitoring for late complications and intensification of infectious prophylaxis remain critical to minimize NRM. Overall, our findings further support cilta-cel as a highly effective therapeutic option with broad applicability in the SOC management of RRMM patients. As cilta-cel is integrated into earlier lines of treatment, future research should prioritize identifying patients at highest risk for treatment-related toxicities, such as NINT, SPM, and IEC-EC, while advancing preventive and therapeutic strategies to enhance its safety in clinical practice.
Supplementary information
Supplemental Material Reproducibility checklist - NOT FOR PUBLICATION
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Doris K. Hansen, Danai Dima, Hira Mian.
These authors jointly supervised this work: Surbhi Sidana, Krina K. Patel.
Change history
8/11/2026
The original online version of this article was revised: In this article the author name ‘Larry D. Anderson, Jr’ has been published as ‘Larry Anderson’.
Change history
8/31/2026
A Correction to this paper has been published: https://doi.org/10.1038/s41408-026-01605-9
Supplementary information
The online version contains supplementary material available at https://doi.org/10.1038/s41408-026-01496-w .
Acknowledgements
The authors would like to acknowledge the patients who participated in this retrospective study, along with their families and caregivers, the physicians and nurses who provided care, the staff members at the CIBMTR, and the personnel involved in data collection at all participating centers.
Author contributions
DKH, DD, HM, OSA, SS, and KKP conceived and designed the study. DKH, DD, JD, TO, RB, and OSA performed data analysis and interpretation. DKH, DD, HM, SS, KKP, and OSA drafted the manuscript. JD, RB, TO, AA, NA, LA, RBan, JGB, AB, BD, AD, YE, MSF, LG, HH, ASM, MM, RN, AER, MS, TN, HL, SU, and MCP critically revised the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work.
Funding
The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI); the National Heart, Lung, and Blood Institute (NHLBI); and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); N00014-24-1-2057 and N00014-25-1-2146 from the Office of Naval Research; NMDP; and the Medical College of Wisconsin. This study was supported by Janssen Biotech, Ltd.
Data availability
Analysis datasets from the Center for International Blood and Marrow Transplant Research (CIBMTR) are freely accessible for secondary analysis, with strict measures in place to safeguard participant privacy and protect confidential and proprietary data: ( https://cibmtr.org/CIBMTR/Resources/Publicly-Available-Datasets# ).
Competing interests
DKH receives research funding from Bristol Myers Squibb, Janssen, Kite Pharma, Karyopharm, and Adaptive Biotech, and reports consulting or advisory roles with Bristol Myers Squibb, Janssen, Legend Biotech, Pfizer, Kite Pharma/Gilead Sciences, AstraZeneca, and Karyopharm. DD reports consulting for Karyopharm and Caribou Biosciences. HM receives honoraria from Bristol Myers Squibb, Pfizer, Janssen, Amgen, Takeda, GSK, FORUS, and Sanofi, and research funding from Pfizer and Janssen. AA receives research funding from AbbVie, Regeneron Pharmaceuticals, K36-Therapeutics, Janssen, and Adaptive Biotech, and honoraria from Karyopharm, Bristol Myers Squibb, Janssen, Sanofi, and Pfizer. NA receives research funding from Kite/Gilead and Pfizer and has consulting or advisory roles with Bristol Myers Squibb, Kite/Gilead, Invivyd Bio, Legend Bio, Johnson & Johnson, Autolus, and ADC Therapeutics; founder of Cortex (non-profit) and board member of USMIRC. LA receives consulting fees and honoraria from Pfizer, Bristol Myers Squibb, BeiGene, Sanofi, Amgen, Karyopharm, Celgene, Prothena, Cellectar, Johnson & Johnson, GSK, and AbbVie, and research funding from Bristol Myers Squibb, BeiGene, Johnson & Johnson, GSK, and AbbVie. RB reports consulting for AbbVie, Adaptive Biotech, Bristol Myers Squibb, Caribou Biosciences, Genentech, Gilead/Kite, GSK, Janssen, Karyopharm, Legend Biotech, Pfizer, Poseida Therapeutics, Sanofi, and SparkCures, and receives research funding from AbbVie, Bristol Myers Squibb, Janssen, Novartis, Pack Health, Prothena, and Sanofi. MM is supported by the Advancing a Healthier Wisconsin CTSI KL2 award, receives institutional research funding from Sanofi, Bristol Myers Squibb, and Celgene, and reports consulting for Sanofi, Bristol Myers Squibb/Celgene, Pfizer, Janssen Scientific Affairs, Legend Biotech, and Adaptive Biotech. SS reports consulting for Janssen, Bristol Myers Squibb, Legend, Magenta Therapeutics, Sanofi, Pfizer, Takeda, Kite, AbbVie, Regeneron, BiolineRx, and Genentech/Roche, and receives research funding from Janssen, Magenta Therapeutics, Allogene Therapeutics, Novartis, and Bristol Myers Squibb. KKP reports consulting for Bristol Myers Squibb, Janssen, Pfizer, Arcellx, and Karyopharm Therapeutics, research funding from Bristol Myers Squibb, Poseida Therapeutics, Takeda, Janssen, Cellectis, Nektar, AbbVie/Genentech, Precision Biosciences, and Allogene Therapeutics, and travel support from Bristol Myers Squibb. ASM reports consulting for Bristol Myers Squibb. MCP receives honoraria from Gilead and research funding from Kite/Gilead, Janssen, Bristol Myers Squibb, and Novartis. HH reports consulting for Bristol Myers Squibb, Sanofi, and Janssen. YE receives honoraria from Pfizer, GSK, Kite, Janssen, Sanofi, Bristol Myers Squibb, Orca, and Oncopeptides, and research funding via Pharmacyclics (Alliance) and GSK (Alliance). BD receives honoraria from Natera, GlaxoSmithKline, Menarini, Kite, and Janssen, consulting for Genentech, Caribou, Johnson & Johnson, Karyopharm, Bristol Myers Squibb, Janssen, Arcellx, and Pfizer, and research funding from Caribou, Ichnos, Kite, Carsgen, Bristol Myers Squibb, Janssen, Arcellx, and Pfizer. SU reports consulting or advisory roles with GSK, Takeda, SecuraBio, Amgen, Seagen, Johnson & Johnson/Janssen, Genentech, Sanofi, Gilead, Oncopeptides, Bristol Myers Squibb/Celgene, SkylineDX, AbbVie, EdoPharma, Gracell Therapeutics, TeneoBio, and AstraZeneca, and receives research funding from Janssen, Takeda, SecuraBio, Amgen, Seagen, Johnson & Johnson/Janssen, Sanofi, Gilead, Oncopeptides, Bristol Myers Squibb/Celgene, SkylineDX, AbbVie, EdoPharma, Gracell Therapeutics, and TeneoBio. OSA reports advisory board participation for Sanofi and Janssen, and consulting for Immix Biopharma. All remaining authors report no financial relationships relevant to this work.
Ethics approval
All Center for International Blood and Marrow Transplant Research studies are reviewed and approved by the National Marrow Donor Program Institutional Review Board, and all patients (or their legal guardians) provided informed consent for data collection and research.
References
1. van de Donk N Pawlyn C Yong KL Multiple myeloma Lancet 2021 397 410 27 10.1016/S0140-6736(21)00135-5 33516340 van de Donk N, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021;397:410–27. 33516340 10.1016/S0140-6736(21)00135-5
2. Nijhof IS van de Donk N Zweegman S Lokhorst HM Current and new therapeutic strategies for relapsed and refractory multiple myeloma: an update Drugs 2018 78 19 37 10.1007/s40265-017-0841-y 29188449 PMC5756574 Nijhof IS, van de Donk N, Zweegman S, Lokhorst HM. Current and new therapeutic strategies for relapsed and refractory multiple myeloma: an update. Drugs. 2018;78:19–37. 29188449 10.1007/s40265-017-0841-y PMC5756574
3. Sonneveld P Broijl A Treatment of relapsed and refractory multiple myeloma Haematologica 2016 101 396 406 10.3324/haematol.2015.129189 27033237 PMC5004403 Sonneveld P, Broijl A. Treatment of relapsed and refractory multiple myeloma. Haematologica. 2016;101:396–406. 27033237 10.3324/haematol.2015.129189 PMC5004403
4. Berdeja JG Madduri D Usmani SZ Jakubowiak A Agha M Cohen AD Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study Lancet 2021 398 314 24 10.1016/S0140-6736(21)00933-8 34175021 Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398:314–24. 34175021 10.1016/S0140-6736(21)00933-8
5. Martin T Usmani SZ Berdeja JG Agha M Cohen AD Hari P Ciltacabtagene autoleucel, an anti–B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up J Clin Oncol 2023 41 1265 74 10.1200/JCO.22.00842 35658469 PMC9937098 Martin T, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P, et al. Ciltacabtagene autoleucel, an anti–B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol. 2023;41:1265–74. 35658469 10.1200/JCO.22.00842 PMC9937098
6. Lin Y Martin TG Usmani SZ Berdeja JG Jakubowiak AJ Agha ME CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma [Meeting Abstract 2023 ASCO Annual Meeting I] J Clin Oncol 2023 41 8009 10.1200/JCO.2023.41.16_suppl.8009 Lin Y, Martin TG, Usmani SZ, Berdeja JG, Jakubowiak AJ, Agha ME, et al. CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma [Meeting Abstract 2023 ASCO Annual Meeting I]. J Clin Oncol. 2023;41:8009 10.1200/JCO.2023.41.16_suppl.8009 . 2023/06/01.
7. San-Miguel J Dhakal B Yong K Spencer A Anguille S Mateos MV Cilta-cel or standard care in lenalidomide-refractory multiple myeloma N Engl J Med 2023 389 335 47 10.1056/NEJMoa2303379 37272512 San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389:335–47. 37272512 10.1056/NEJMoa2303379
8. Jagannath S Martin TG Lin Y Cohen AD Raje N Htut M Long-term (≥5-year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma J Clin Oncol 2025 43 2766 71 10.1200/JCO-25-00760 40459151 PMC12393059 Jagannath S, Martin TG, Lin Y, Cohen AD, Raje N, Htut M, et al. Long-term (≥5-year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2025;43:2766–71. 40459151 10.1200/JCO-25-00760 PMC12393059
9. Dima D Rashid A Davis JA Shune L Abdallah AO Li H Efficacy and safety of idecabtagene vicleucel in patients with relapsed-refractory multiple myeloma not meeting the KarMMa-1 trial eligibility criteria: A real-world multicentre study Br J Haematol 2024 204 1293 9 10.1111/bjh.19302 38263627 Dima D, Rashid A, Davis JA, Shune L, Abdallah AO, Li H, et al. Efficacy and safety of idecabtagene vicleucel in patients with relapsed-refractory multiple myeloma not meeting the KarMMa-1 trial eligibility criteria: A real-world multicentre study. Br J Haematol. 2024;204:1293–9. 38263627 10.1111/bjh.19302
10. Hansen DK Sidana S Peres LC Colin Leitzinger C Shune L Shrewsbury A Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the Myeloma CAR T Consortium J Clin Oncol 2023 41 2087 97 10.1200/JCO.22.01365 36623248 PMC10082273 Hansen DK, Sidana S, Peres LC, Colin Leitzinger C, Shune L, Shrewsbury A, et al. Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the Myeloma CAR T Consortium. J Clin Oncol. 2023;41:2087–97. 36623248 10.1200/JCO.22.01365 PMC10082273
11. Sidana S Patel KK Peres LC Bansal R Kocoglu MH Shune L Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma Blood 2025 145 85 97 10.1182/blood.2024025945 39365257 PMC11952008 Sidana S, Patel KK, Peres LC, Bansal R, Kocoglu MH, Shune L, et al. Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma. Blood. 2025;145:85–97. 39365257 10.1182/blood.2024025945 PMC11952008
12. Sidana S Ahmed N Akhtar OS Brazauskas R Oloyede T Bye M Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma Blood 2025 146 167 77 10.1182/blood.2024026216 40198886 PMC12964216 Sidana S, Ahmed N, Akhtar OS, Brazauskas R, Oloyede T, Bye M, et al. Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma. Blood. 2025;146:167–77. 40198886 10.1182/blood.2024026216 PMC12964216
13. Hansen DK Peres LC Dima D Richards A Shune L Afrough A Comparison of standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma J Clin Oncol 2025 43 1597 609 10.1200/JCO-24-01730 39965175 PMC12037312 Hansen DK, Peres LC, Dima D, Richards A, Shune L, Afrough A, et al. Comparison of standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma. J Clin Oncol. 2025;43:1597–609. 39965175 10.1200/JCO-24-01730 PMC12037312
14. Sidana S Peres LC Hashmi H Hosoya H Ferreri C Khouri J Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment Haematologica 2024 109 777 86 10.3324/haematol.2023.283940 37731379 PMC10905101 Sidana S, Peres LC, Hashmi H, Hosoya H, Ferreri C, Khouri J, et al. Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment. Haematologica. 2024;109:777–86. 37731379 10.3324/haematol.2023.283940 PMC10905101
15. Zanwar S Sidana S Shune L Puglianini OC Pasvolsky O Gonzalez R Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel J Hematol Oncol 2024 17 42 10.1186/s13045-024-01555-4 38845015 PMC11157748 Zanwar S, Sidana S, Shune L, Puglianini OC, Pasvolsky O, Gonzalez R, et al. Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel. J Hematol Oncol. 2024;17:42. 38845015 10.1186/s13045-024-01555-4 PMC11157748
16. Lee DW Santomasso BD Locke FL Ghobadi A Turtle CJ Brudno JN ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells Biol Blood Marrow Transplant 2019 25 625 38 10.1016/j.bbmt.2018.12.758 30592986 PMC12180426 Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625–38. 30592986 10.1016/j.bbmt.2018.12.758 PMC12180426
17. Kumar S Paiva B Anderson KC Durie B Landgren O Moreau P International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma Lancet Oncol 2016 17 e328 e46 10.1016/S1470-2045(16)30206-6 27511158 Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328–e46. 27511158 10.1016/S1470-2045(16)30206-6
18. Cohen AD Mateos MV Cohen YC Rodriguez-Otero P Paiva B van de Donk N Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents Blood 2023 141 219 30 10.1182/blood.2022015526 36095849 PMC10562529 Cohen AD, Mateos MV, Cohen YC, Rodriguez-Otero P, Paiva B, van de Donk N, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023;141:219–30. 36095849 10.1182/blood.2022015526 PMC10562529
19. Dima D Davis JA Ahmed N Jia X Sannareddy A Shaikh H Safety and efficacy of teclistamab in patients with relapsed/refractory multiple myeloma: A real-world experience Transplant Cell Ther 2024 30 308.e1 .e13 10.1016/j.jtct.2023.12.016 38151105 Dima D, Davis JA, Ahmed N, Jia X, Sannareddy A, Shaikh H, et al. Safety and efficacy of teclistamab in patients with relapsed/refractory multiple myeloma: A real-world experience. Transplant Cell Ther. 2024;30:308.e1–.e13. 38151105 10.1016/j.jtct.2023.12.016
20. Dima D Vazquez-Martinez MA Davis JA Goel U Afrough A Sannareddy A Outcomes of teclistamab in patients with relapsed/refractory multiple myeloma with prior exposure to BCMA-directed therapy: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium Blood Cancer J 2025 15 111 10.1038/s41408-025-01314-9 40562770 PMC12198414 Dima D, Vazquez-Martinez MA, Davis JA, Goel U, Afrough A, Sannareddy A, et al. Outcomes of teclistamab in patients with relapsed/refractory multiple myeloma with prior exposure to BCMA-directed therapy: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium. Blood Cancer J. 2025;15:111. 40562770 10.1038/s41408-025-01314-9 PMC12198414
21. Razzo, BM, Midha, S, Portuguese, AJ, Grajales-Cruz, AF, De Menezes Silva Corraes, A, Costello, P, et al. Real-world experience with teclistamab for relapsed/refractory multiple myeloma from the U.S. Myeloma Immunotherapy Consortium. Blood Cancer Discov. 2025;6:561–71. 10.1158/2643-3230.BCD-24-0354 40629516
22. Ferreri CJ Hildebrandt MAT Hashmi H Shune LO McGuirk JP Sborov DW Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy Blood Cancer J 2023 13 117 10.1038/s41408-023-00886-8 37558706 PMC10412575 Ferreri CJ, Hildebrandt MAT, Hashmi H, Shune LO, McGuirk JP, Sborov DW, et al. Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy. Blood Cancer J. 2023;13:117. 37558706 10.1038/s41408-023-00886-8 PMC10412575
23. Ferment B Lambert J Caillot D Lafon I Karlin L Lazareth A French early nationwide idecabtagene vicleucel chimeric antigen receptor T-cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): A real-world IFM study from the DESCAR-T registry Br J Haematol 2024 205 990 8 10.1111/bjh.19505 38747092 Ferment B, Lambert J, Caillot D, Lafon I, Karlin L, Lazareth A, et al. French early nationwide idecabtagene vicleucel chimeric antigen receptor T-cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): A real-world IFM study from the DESCAR-T registry. Br J Haematol. 2024;205:990–8. 38747092 10.1111/bjh.19505
24. Costa LJ Banerjee R Mian H Weisel K Bal S Derman BA International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma Leukemia 2025 39 543 54 10.1038/s41375-024-02482-6 39870767 PMC11879857 Costa LJ, Banerjee R, Mian H, Weisel K, Bal S, Derman BA, et al. International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma. Leukemia. 2025;39:543–54. 39870767 10.1038/s41375-024-02482-6 PMC11879857
25. Maura F Freeman CL Lee H Maclachlan KH Durante M Ziccheddu B Genomic determinants of resistance to anti-BCMA chimeric antigen receptor T-cell (CART) therapies in patients with relapsed/refractory multiple myeloma Blood 2024 144 247 10.1182/blood-2024-201288 Maura F, Freeman CL, Lee H, Maclachlan KH, Durante M, Ziccheddu B, et al. Genomic determinants of resistance to anti-BCMA chimeric antigen receptor T-cell (CART) therapies in patients with relapsed/refractory multiple myeloma. Blood. 2024;144:247.39023873
26. Lee H Ahn S Maity R Leblay N Ziccheddu B Truger M Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma Nat Med 2023 29 2295 306 10.1038/s41591-023-02491-5 37653344 PMC10504087 Lee H, Ahn S, Maity R, Leblay N, Ziccheddu B, Truger M, et al. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. Nat Med. 2023;29:2295–306. 37653344 10.1038/s41591-023-02491-5 PMC10504087
27. Hashmi H Hansen DK Peres LC Puglianini OC Freeman C De Avila G Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma: US myeloma immunotherapy consortium real world experience Haematologica 2024 109 1514 24 37855036 10.3324/haematol.2023.283888 PMC11063864 Hashmi H, Hansen DK, Peres LC, Puglianini OC, Freeman C, De Avila G, et al. Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma: US myeloma immunotherapy consortium real world experience. Haematologica. 2024;109:1514–24. 37855036 10.3324/haematol.2023.283888 PMC11063864
28. Gagelmann N Dima D Merz M Hashmi H Ahmed N Tovar N Development and validation of a prediction model of outcome after B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in relapsed/refractory multiple myeloma J Clin Oncol 2024 42 1665 75 10.1200/JCO.23.02232 38358946 PMC11095856 Gagelmann N, Dima D, Merz M, Hashmi H, Ahmed N, Tovar N, et al. Development and validation of a prediction model of outcome after B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42:1665–75. 38358946 10.1200/JCO.23.02232 PMC11095856
29. Freeman CL Noble J Menges M Villanueva R Nakashima JY Figura NB Tumor burden quantified by soluble B-cell maturation antigen and metabolic tumor volume determines myeloma CAR-T outcomes Blood 2025 145 1645 57 10.1182/blood.2024024965 39652773 Freeman CL, Noble J, Menges M, Villanueva R, Nakashima JY, Figura NB, et al. Tumor burden quantified by soluble B-cell maturation antigen and metabolic tumor volume determines myeloma CAR-T outcomes. Blood. 2025;145:1645–57. 39652773 10.1182/blood.2024024965
30. Rodriguez-Otero P Ailawadhi S Arnulf B Patel K Cavo M Nooka AK Ide-cel or standard regimens in relapsed and refractory multiple myeloma N Engl J Med 2023 388 1002 14 10.1056/NEJMoa2213614 36762851 Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388:1002–14. 36762851 10.1056/NEJMoa2213614
31. Portuguese AJ Liang EC Huang JJ Jeon Y Dima D Banerjee R et al. Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma. Haematologica. 2025;110:3065–077. 10.3324/haematol.2025.287985 PMC12666262 40534492
32. Ailawadhi S Anderson LD Dhakal B Shune L Sborov DW Hansen DK. Optimizing selection of bridging therapies prior to CAR-T therapy administration for multiple myeloma: clinical pearls from an expert roundtable. Clin Lymphoma Myeloma Leuk. 2025;26:85–93. 10.1016/j.clml.2025.08.005 40885679
33. Einsele H Rodriguez-Otero P Arnulf B Patel K Manier S Costa L P-008 Idecabtagene vicleucel (ide-cel) vs standard regimens in triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): KarMMa-3 subgroup analysis in patients receiving bridging therapy Clin Lymphoma Myeloma Leuk 2023 23 S37 10.1016/S2152-2650(23)01626-9 Einsele H, Rodriguez-Otero P, Arnulf B, Patel K, Manier S, Costa L, et al. P-008 Idecabtagene vicleucel (ide-cel) vs standard regimens in triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): KarMMa-3 subgroup analysis in patients receiving bridging therapy. Clin Lymphoma Myeloma Leuk. 2023;23:S37.
34. Lin Y Leleu X Gatt M Karlin L Spencer A Iida S MM-522 effectiveness of bridging therapy corresponds to improved outcomes after receiving CAR-T therapy: Phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma Clin Lymphoma Myeloma Leuk 2024 24 S566 S7 10.1016/S2152-2650(24)01698-7 Lin Y, Leleu X, Gatt M, Karlin L, Spencer A, Iida S, et al. MM-522 effectiveness of bridging therapy corresponds to improved outcomes after receiving CAR-T therapy: Phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2024;24:S566–S7.
35. Afrough A Hashmi H Hansen DK Sidana S Ahn C Peres LC Real-world impact of bridging therapy on outcomes of ide-cel for myeloma in the U.S. Myeloma Immunotherapy Consortium Blood Cancer J 2024 14 63 10.1038/s41408-024-00993-0 38609386 PMC11015040 Afrough A, Hashmi H, Hansen DK, Sidana S, Ahn C, Peres LC, et al. Real-world impact of bridging therapy on outcomes of ide-cel for myeloma in the U.S. Myeloma Immunotherapy Consortium. Blood Cancer J. 2024;14:63. 38609386 10.1038/s41408-024-00993-0 PMC11015040
36. Midha S Gurumurthi A Costello P Redd RA Freeman CLL Castaneda O Alternative lymphodepletion strategies lead to similar response rates and toxicities in standard-of-care BCMA-directed CAR-T therapy in relapsed refractory multiple myeloma [Abstract from the 65th ASH Annual Meeting] Blood 2023 142 3499 10.1182/blood-2023-187565 Midha S, Gurumurthi A, Costello P, Redd RA, Freeman CLL, Castaneda O, et al. Alternative lymphodepletion strategies lead to similar response rates and toxicities in standard-of-care BCMA-directed CAR-T therapy in relapsed refractory multiple myeloma [Abstract from the 65th ASH Annual Meeting]. Blood. 2023;142:3499. 10.1182/blood-2023-187565 .
37. Ramos CA Grover NS Beaven AW Lulla PD Wu MF Ivanova A Anti-CD30 CAR-T cell therapy in relapsed and refractory hodgkin lymphoma J Clin Oncol 2020 38 3794 804 10.1200/JCO.20.01342 32701411 PMC7655020 Ramos CA, Grover NS, Beaven AW, Lulla PD, Wu MF, Ivanova A, et al. Anti-CD30 CAR-T cell therapy in relapsed and refractory hodgkin lymphoma. J Clin Oncol. 2020;38:3794–804. 32701411 10.1200/JCO.20.01342 PMC7655020
38. Janssen Pharma: CARVYKTI (ciltacabtagene autoleucel). Package insert. Accessed 13 June 2023. https://www.fda.gov/media/156560/download .
39. Van De Donk NW Sidana S Schecter JM Jackson CC Lendvai N De Braganca KC Clinical experience with cranial nerve impairment in the CARTITUDE-1, CARTITUDE-2 cohorts A, B, and C, and cartitude-4 studies of ciltacabtagene autoleucel (cilta-cel) [Abstract 65th ASH Annual Meeting] Blood 2023 142 3501 10.1182/blood-2023-178743 Van De Donk NW, Sidana S, Schecter JM, Jackson CC, Lendvai N, De Braganca KC, et al. Clinical experience with cranial nerve impairment in the CARTITUDE-1, CARTITUDE-2 cohorts A, B, and C, and cartitude-4 studies of ciltacabtagene autoleucel (cilta-cel) [Abstract 65th ASH Annual Meeting]. Blood. 2023;142:3501. 10.1182/blood-2023-178743 .
40. Cohen AD Parekh S Santomasso BD Gállego Pérez-Larraya J van de Donk N Arnulf B Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies Blood Cancer J 2022 12 32 10.1038/s41408-022-00629-1 35210399 PMC8873238 Cohen AD, Parekh S, Santomasso BD, Gállego Pérez-Larraya J, van de Donk N, Arnulf B, et al. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J. 2022;12:32. 35210399 10.1038/s41408-022-00629-1 PMC8873238
41. Kelly K Cooperrider JH Bishop MR Kosuri S Jakubowiak A Derman BA Intrathecal chemotherapy for ciltacabtagene autoleucel-associated movement and neurocognitive toxicity Blood Adv 2025 9 3613 6 10.1182/bloodadvances.2024015721 40334078 PMC12281119 Kelly K, Cooperrider JH, Bishop MR, Kosuri S, Jakubowiak A, Derman BA. Intrathecal chemotherapy for ciltacabtagene autoleucel-associated movement and neurocognitive toxicity. Blood Adv. 2025;9:3613–6. 40334078 10.1182/bloodadvances.2024015721 PMC12281119
42. Graham CE Lee WH Wiggin HR Supper VM Leick MB Birocchi F Chemotherapy-induced reversal of ciltacabtagene autoleucel-associated movement and neurocognitive toxicity Blood 2023 142 1248 52 10.1182/blood.2023021429 37467494 PMC10579042 Graham CE, Lee WH, Wiggin HR, Supper VM, Leick MB, Birocchi F, et al. Chemotherapy-induced reversal of ciltacabtagene autoleucel-associated movement and neurocognitive toxicity. Blood. 2023;142:1248–52. 37467494 10.1182/blood.2023021429 PMC10579042
43. Gust J BCMA-CAR T-cell treatment–associated parkinsonism Blood 2023 142 1181 3 10.1182/blood.2023021860 37796518 Gust J. BCMA-CAR T-cell treatment–associated parkinsonism. Blood. 2023;142:1181–3. 37796518 10.1182/blood.2023021860
44. Hosoya H Velayati A Dima D Jensen A Portuguese A Hovanky V Rapid peak CAR-T expansion is associated with delayed neurotoxicity following ciltacabtagene autoleucel in multiple myeloma Clin Lymphoma Myeloma Leuk 2025 25 S4 10.1016/S2152-2650(25)03409-3 Hosoya H, Velayati A, Dima D, Jensen A, Portuguese A, Hovanky V, et al. Rapid peak CAR-T expansion is associated with delayed neurotoxicity following ciltacabtagene autoleucel in multiple myeloma. Clin Lymphoma Myeloma Leuk. 2025;25:S4.
45. Lim KJ Parrondo R Chhabra S Dooley K De Menezes Silva Corraes A Carabenciov D Prophylactic dexamethasone to reduce risk of cilta-cel associated immune effector cell delayed neurotoxicity Blood 2025 146 5953 10.1182/blood-2025-5953 Lim KJ, Parrondo R, Chhabra S, Dooley K, De Menezes Silva Corraes A, Carabenciov D, et al. Prophylactic dexamethasone to reduce risk of cilta-cel associated immune effector cell delayed neurotoxicity. Blood. 2025;146:5953.
46. Feliciano Salva K Copponex C Whiting J Hansen D Freeman CL Castaneda Puglianini OA Suppressive dexamethasone (SupDex) to prevent delayed non-icans delayed neurotoxicity (DNT) post ciltacabtagene-autoleucel(cilta-cel) in patients with relapsed myeloma.suppressive dexamethasone (SupDex) to prevent delayed non-icans delayed neurotoxicity (DNT) post ciltacabtagene-autoleucel(cilta-cel) in patients with relapsed myeloma Blood 2025 146 5856 10.1182/blood-2025-5856 Feliciano Salva K, Copponex C, Whiting J, Hansen D, Freeman CL, Castaneda Puglianini OA, et al. Suppressive dexamethasone (SupDex) to prevent delayed non-icans delayed neurotoxicity (DNT) post ciltacabtagene-autoleucel(cilta-cel) in patients with relapsed myeloma.suppressive dexamethasone (SupDex) to prevent delayed non-icans delayed neurotoxicity (DNT) post ciltacabtagene-autoleucel(cilta-cel) in patients with relapsed myeloma. Blood. 2025;146:5856.
47. U.S. Food & Drug Administration (FDA). FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T-cell Immunotherapies [Internet]. Washington DC; 2023. Available from: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous .
48. Harrison SJ Nguyen T Rahman M Er J Li J Li K CAR+ T-cell lymphoma post ciltacabtagene autoleucel therapy for relapsed refractory multiple myeloma [Abstract from the 65th ASH Annual Meeting] Blood 2023 142 6939 10.1182/blood-2023-178806 Harrison SJ, Nguyen T, Rahman M, Er J, Li J, Li K, et al. CAR+ T-cell lymphoma post ciltacabtagene autoleucel therapy for relapsed refractory multiple myeloma [Abstract from the 65th ASH Annual Meeting]. Blood. 2023;142:6939. 10.1182/blood-2023-178806 .
49. Elsallab M Ellithi M Lunning MA Perales MA D’Angelo C Ma J Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA adverse events reporting system Blood 2024 143 2099 105 10.1182/blood.2024024166 38483155 Elsallab M, Ellithi M, Lunning MA, Perales MA, D’Angelo C, Ma J, et al. Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA adverse events reporting system. Blood. 2024;143:2099–105. 38483155 10.1182/blood.2024024166
50. Ghilardi G Fraietta JA Gerson JN Van Deerlin VM Morrissette JJD Caponetti GC T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy Nat Med 2024 30 984 9 10.1038/s41591-024-02826-w 38266761 Ghilardi G, Fraietta JA, Gerson JN, Van Deerlin VM, Morrissette JJD, Caponetti GC, et al. T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy. Nat Med. 2024;30:984–9. 38266761 10.1038/s41591-024-02826-w
51. Ozdemirli M Loughney TM Deniz E Chahine JJ Albitar M Pittaluga S Indolent CD4+ CAR T-cell lymphoma after cilta-cel CAR T-cell therapy N Engl J Med 2024 390 2074 82 10.1056/NEJMoa2401530 38865661 Ozdemirli M, Loughney TM, Deniz E, Chahine JJ, Albitar M, Pittaluga S, et al. Indolent CD4+ CAR T-cell lymphoma after cilta-cel CAR T-cell therapy. N Engl J Med. 2024;390:2074–82. 38865661 10.1056/NEJMoa2401530
52. Perica K Jain N Scordo M Patel R Eren OC Patel U CD4+ T-cell lymphoma harboring a chimeric antigen receptor integration in TP53 N Engl J Med 2025 392 577 83 10.1056/NEJMoa2411507 39908432 PMC11801235 Perica K, Jain N, Scordo M, Patel R, Eren OC, Patel U, et al. CD4+ T-cell lymphoma harboring a chimeric antigen receptor integration in TP53. N Engl J Med. 2025;392:577–83. 39908432 10.1056/NEJMoa2411507 PMC11801235
53. Cordas Dos Santos DM Tix T Shouval R Gafter-Gvili A Alberge JB Cliff ERS A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy Nat Med 2024 30 2667 78 10.1038/s41591-024-03084-6 38977912 PMC11765209 Cordas Dos Santos DM, Tix T, Shouval R, Gafter-Gvili A, Alberge JB, Cliff ERS, et al. A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy. Nat Med. 2024;30:2667–78. 38977912 10.1038/s41591-024-03084-6 PMC11765209
54. Dima D Logue JM Waqar SHB Peres LC Colin-Leitzinger CM De Avila G Cytopenias and infections following ciltacabtagene autoleucel in heavily pretreated relapsed or refractory multiple myeloma Haematologica 2026 111 184 95 40637727 10.3324/haematol.2025.287783 PMC12775792 Dima D, Logue JM, Waqar SHB, Peres LC, Colin-Leitzinger CM, De Avila G, et al. Cytopenias and infections following ciltacabtagene autoleucel in heavily pretreated relapsed or refractory multiple myeloma. Haematologica. 2026;111:184–95. 40637727 10.3324/haematol.2025.287783 PMC12775792