CARVYKTI – Real-world Efficacy and Safety Outcomes

SUMMARY

• Johnson & Johnson does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• Summarized in this response are key real-world studies evaluating the overall efficacy and safety of CARVYKTI in >100 patients with multiple myeloma (MM) and relapsed or refractory multiple myeloma (RRMM).^1-7
• Real-world studies evaluating patients who received CARVYKTI in early- and late-line treatment settings:
  • Gagelmann et al (2026)¹ published a nationwide registry analysis from the German Registry for Stem Cell Transplantation and Cellular Therapy evaluating the effectiveness and safety of CARVYKTI in 606 patients with RRMM, including outcomes among patients treated after 1-3 vs >3 prior lines of therapy (LOTs).
  • Lim et al (2026)² presented a retrospective multicenter analysis evaluating real-world outcomes and risk factors in 230 patients with MM treated with CARVYKTI at Mayo Clinic Rochester, Arizona, and Florida.
• Real-world studies evaluating patients who received CARVYKTI in late-line treatment setting:
  • Hansen et al (2026)³ published a retrospective registry analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) evaluating the efficacy and safety of CARVYKTI in 595 patients with RRMM.
  • Mian et al (2025)⁴ presented a CIBMTR cohort study evaluating the efficacy and safety of CARVYKTI in 541 patients with RRMM, with outcomes stratified by frailty status using a simplified frailty index.
  • Sidana et al (2025)⁵ presented a multicenter retrospective study evaluating the efficacy and safety of CARVYKTI in 236 patients with RRMM treated across 16 United States (US) academic centers.
  • Sidana et al (2023)⁶ presented a multicenter study evaluating real-world outcomes with intended CARVYKTI in 153 patients undergoing apheresis across 14 US academic centers, including 143 patients who received CARVYKTI infusion.
• Reshef et al (2025)⁷ presented a multicenter retrospective analysis evaluating the association between CARVYKTI dose and clinical outcomes in 751 patients with RRMM treated across 15 US academic centers.

PRODUCT LABELING

• CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf.
• TALVEY (talquetamab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf

Efficacy and Safety in Early-line and Late-line Patients

German Registry Analysis of CARVYKTI by Prior LOTs

Gagelmann et al (2026)¹ published a nationwide registry analysis from the German Registry for Stem Cell Transplantation and Cellular Therapy evaluating the effectiveness and safety of CARVYKTI in 606 patients with RRMM treated between 2022 and 2025. Patients were stratified according to prior LOTs into an early-line cohort (1-3 prior LOTs; n=177) and a late-line cohort (>3 prior LOTs; n=429).

• Median follow-up was 7.2 months (95% confidence interval [CI], 6.4-10.1) in the early-line cohort and 11.0 months (95% CI, 8.8-11.9) in the late-line cohort.
• The median age was 64 years in both cohorts. Compared with the late-line cohort, the early-line cohort had received fewer prior LOTs (median, 2 vs 5), had a higher prevalence of high-risk cytogenetic abnormalities (47% vs 37%), a lower prevalence of ISS stage III disease (40% vs 46%), and less extramedullary disease (EMD; 20% vs 27%). Most patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
• Early-line cohort:
  • The overall response rate (ORR) was 91%, with 63% of patients achieving a complete response (CR). The 6-month and 12-month progression-free survival (PFS) rates were 90% (95% CI, 84-95) and 79% (95% CI, 71-87), respectively.
    • The 6-month and 12-month PFS rates were 86% and 74%, respectively, among functionally high-risk (FHR) patients, compared with 91% and 82%, among non-FHR patients (hazard ratio [HR], 1.35; 95% CI, 0.63-2.90).
    • The association between response depth and PFS was pronounced in both cohorts. Patients who maintained CR showed a 12-month PFS rate of 100%, regardless of treatment line. Poor outcomes were observed in patients who entered CARVYKTI treatment with less than a partial response (PR) and who did not achieve a response.
  • Grade 1 and 2 cytokine release syndrome (CRS) occurred in 42% and 28% of patients, respectively. Grade ≥3 CRS was uncommon.
  • Grade ≥2 immune effector cell-associated neurotoxicity syndrome (ICANS) and non-ICANS neurotoxicity were reported in 4% and 3% of patients, respectively.
  • The cumulative incidence of nonrelapse mortality (NRM) at 6 and 12 months was 2.7% and 7.6%, respectively.
• Late-line cohort:
  • The ORR was 88%, with 54% of patients achieving a CR. The 6-month and 12-month PFS rates were 88% (95% CI, 84-91) and 70% (95% CI, 65-76), respectively, and the median PFS was 21.2 months.
    • The 6-month and 12-month PFS rates were 81% and 63%, respectively, among FHR patients, compared with 89% and 71% among non-FHR patients (HR, 1.69; 95% CI, 1.06-2.70).
  • Grade 1 and 2 CRS occurred in 40% and 30% of patients, respectively. Grade ≥3 CRS was uncommon.
  • Grade ≥2 ICANS and non-ICANS neurotoxicity were reported in 2% and 8% of patients, respectively, including 1 fatal grade 5 ICANS event.
  • The cumulative incidence of NRM at 6 and 12 months was 2.3% and 6.3%, respectively.
• Among 159 patients (26%) who received bridging therapy, proteasome inhibitor-based triplets were the most used regimens (49%) followed by anti-cluster of differentiation (CD) 38 antibody-containing (35%), immunomodulatory drug-containing (31%), and elotuzumab-containing regimens (15%). Talquetamab-containing bridging therapy was administered to 35 patients (6%), all of whom were in the late-line setting.
  • In the early-line bridging cohort, the 6-month and 12-month PFS rates were 87% and 79%, respectively.
  • In the late-line bridging cohort, the 6-month and 12-month PFS rates were 87% and 70%, respectively.
  • Among patients who received talquetamab-containing bridging therapy, the 6-month and 12-month PFS rates were 82% and 69%, respectively.

Mayo Clinic Analysis of CARVYKTI Outcomes and Prognostic Factors

Lim et al (2026)² presented a retrospective multicenter analysis evaluating real-world outcomes and risk factors in 230 patients with MM treated with CARVYKTI at Mayo Clinic sites in Rochester, Arizona, and Florida between February 2022 and November 2024.

• The median follow-up was 14 months (95% CI, 12-16).
• Overall, 32% of patients had received 1-3 prior LOTs.
• The median age was 65 years (range, 31-86); 71% of patients were triple-class refractory, 25% were penta-drug refractory, and 28% had FHR disease.
• The ORR was 86%. Median PFS and overall survival (OS) were not reached, and the estimated 12-month PFS and OS rates were 77% and 87%, respectively.
  • On univariate analysis, FHR status, 1q+, ≥2 HRCAs, EMD, triple-class refractoriness and penta-drug refractoriness, prior B-cell maturation antigen (BCMA) exposure, a high CAR-HEMATOTOX score, and any-grade ICANS after infusion were associated with inferior PFS.
  • On multivariable analysis, ≥2 HRCAs, EMD, penta-drug refractoriness, prior BCMA exposure, a high CAR-HEMATOTOX score, and any-grade ICANS remained associated with inferior PFS, whereas FHR status and triple-class refractoriness were no longer significant.
• CRS and ICANS were reported in 78% and 11% of patients, respectively, with grade ≥3 events reported in 1% of patients for each event. At the median follow-up, 59 patients had died or progressed, and the NRM was 6%.

CLINICAL DATA - Efficacy and Safety in Late-line Patients

CIBMTR Registry Outcomes With CARVYKTI in RRMM

Hansen et al (2026)³ published a retrospective worldwide registry analysis evaluating the safety and efficacy of CARVYKTI in 595 patients with RRMM reported to the CIBMTR between March 2022 and December 2023.

• The median follow-up was 12 months (range, 1.1-25.4).
• All patients had received ≥4 prior LOTs and met commercial release specifications for CARVYKTI.
• The median age was 64 years (range, 34-84), 57% of patients were male, and 70% had ≥1 clinically significant comorbidity.
  • Patients had received a median of 7 prior LOTs (range, 4-24); 85% were triple-class exposed, 55% were penta-drug exposed, and 8% had received prior BCMA-directed therapy.
  • High-risk cytogenetics, ISS stage II-III disease, EMD, and a bone marrow plasma cell (BMPC) burden of ≥50% were reported in 27%, 40%, 13%, and 14% of patients, respectively. Most patients (89%) had an ECOG PS of 0-1.
• The ORR was 87%, with 75% of patients achieving a very good partial response or better (≥VGPR) and 35% achieving a CR or better (≥CR). The 12-month PFS and OS rates were 73% (95% CI, 68-77) and 85% (95% CI, 81-88), respectively; median PFS and OS were not reached.
  • Among patients with prior BCMA-directed therapy, the ORR was 70%, with 17% of patients achieving a CR. In patients without and with prior BCMA exposure, the 12-month PFS rates were 74% and 51%, respectively, and the 12-month OS rates were 85% and 81%, respectively.
  • Among patients with EMD, the ORR was 77%, with 40% of patients achieving a CR. In patients without and with EMD, the 12-month PFS rates were 72% and 58%, respectively, and the 12-month OS rates were 85% and 81%, respectively.
  • Among patients with high-risk cytogenetics, the ORR was 88%, with 31% of patients achieving a CR. In patients with standard-risk and high-risk cytogenetics, the 12-month PFS rates were 76% and 63%, respectively, and the 12-month OS rates were 84% in both groups.
• Any-grade CRS was reported in 80% of patients, with grade ≥3 CRS reported in 4%. The median time to onset of CRS was 8 days, and 4 grade 5 CRS events were reported. Any-grade ICANS was reported in 22% of patients, with grade ≥3 ICANS reported in 4%. The median time to onset of ICANS was 9 days, and 2 grade 5 ICANS events were reported. Non-ICANS neurotoxicity was reported in 5% of patients. Parkinsonism and motor neuron disorders (all of which were cranial nerve palsies) reported in 2.7% and 2.5% of patients, respectively. Immune effector cell-associated hemophagocytic syndrome (IEC-HS) and clinically significant infections were reported in 4% and 47% of patients, respectively. Prolonged cytopenias at day 30 were reported in 24% of patients. At the time of analysis, 91 patients (15%) had died, including 53 (9%) due to disease progression, 27 (5%) due to treatment-related mortality (TRM), and 11 from unknown causes. The cumulative incidence of TRM at 12 months was 5% (95% CI, 3-7), with infections accounting for the highest number of treatment-related deaths (n=11).

CIBMTR Analysis of CARVYKTI Outcomes by Frailty Status

Mian et al (2025)⁴ presented a retrospective cohort study evaluating the efficacy and safety of CARVYKTI in patients with RRMM reported to the CIBMTR between
March 2022 and August 2024. Frailty status was available for 541 of 595 treated patients; 183 patients (33.8%) were classified as frail and 358 patients (66.2%) as non-frail based on a simplified frailty index.

• The median follow-up was 12 months.
• Overall, patients received a median of 7 prior LOTs (range, 4-24).
• The median age was 65.5 years (range, 38-84) among frail patients and 63 years (range, 34-80) among non-frail patients; high-risk cytogenetics were reported in 25.1% of patients and prior BCMA exposure in 7.6%, with no significant differences between frail and non-frail patients.
• In frail vs non-frail patients, the ORR was 82.9% vs 88.5%. The 12-month PFS rates were 62.7% (95% CI, 53.6-71.3) vs 75.9% (95% CI, 70.4-81.1). The 12-month OS rates were 72.8% (95% CI, 64.9-80.0) vs 90.4% (95% CI, 86.6-93.7), respectively.
  • Frail patients had significantly worse PFS (HR, 1.67 [95% CI, 1.16-2.40]; P=0.0059) and OS (HR, 2.46 [95% CI, 1.57-3.87]; P<0.0001).
• CRS was reported in 434 patients (80.2%). Neurotoxicity was reported in 141 patients (26.1%). In frail vs non-frail patients, grade ≥2 CRS was reported in 22.4% vs 17.9% of patients, respectively. Any-grade ICANS was reported in 32.2% vs 17.6% of frail vs non-frail patients and grade ≥2 neurotoxicity was reported in 11.5% vs 5.0% of frail vs non-frail patients, respectively. Cranial nerve palsies and parkinsonism developed among 2.6% and 2.8% of frail vs non-frail patients, respectively. Prolonged cytopenias were reported in 30.6% vs 21.2% of frail vs non-frail patients, whereas rates of macrophage activation syndrome/hemophagocytic lymphohistiocytosis (HLH) and clinically significant infections were similar between frail vs non-frail groups (3.7% and 47.0%, respectively). Secondary malignancies were reported in 23 patients (4.5%), with comparable incidence across frail and non-frail groups.
  • The 12-month TRM rates were 6.8% (95% CI, 3.4-11.2) among frail patients and 3.6% (95% CI, 1.8-6.1) among non-frail patients (P=0.11). During follow-up, 82 patients (15.2%) died, including 45 frail patients and 37 non-frail patients. Disease progression was the most common cause of death, accounting for 57.8% of deaths among frail patients and 62.2% among non-frail patients, followed by infections (13.3% and 8.1% of deaths, respectively). ICANS-related deaths were reported only among frail patients (n=2), whereas 1 CRS-related death was reported in each group.

Multicenter US Experience With CARVYKTI in RRMM

Sidana et al (2025)⁵ presented a multicenter retrospective study evaluating the efficacy and safety of CARVYKTI in patients with RRMM across 16 US academic centers. Overall, 255 patients underwent leukapheresis between March 1, 2022, and December 31, 2022, of whom 236 (92.5%) received a CARVYKTI infusion.

• The median follow-up from CARVYKTI infusion was 13.0 months (range, 0.3-21.8).
• Patients received a median of 6 prior LOTs (range, 2-18).
• The median age was 64 years (range, 30-84), with 26% of patients aged ≥70 years. High-risk cytogenetics, EMD, and a BMPC burden ≥50% were reported in 39%, 26%, and 18% of patients, respectively. Overall, 69% were triple-class refractory, 30% were penta-refractory, and 14% had received prior BCMA-directed therapy. Most patients had an ECOG PS of 0-1 at lymphodepletion (89%), and 54% would not have met the CARTITUDE-1 eligibility criteria.
• Among patients who received CARVYKTI (N=236), the ORR was 89%, with 70% achieving a ≥CR. The 12-month estimated PFS and OS rates were 68% (95% CI, 62-74) and 82% (95% CI, 77-87), respectively; median PFS and OS were not reached. Among the 98 patients with measurable residual disease (MRD) assessment who achieved a ≥CR, 95% were MRD negative.
  • Among patients with vs without prior BCMA-directed therapy, the ORR was 70% vs 92%, respectively, and the stringent CR (sCR) or CR rate was 42% vs 75%, respectively; median PFS in patients with prior BCMA-directed therapy was 13.6 months.
  • Among patients with available data on the timing of prior BCMA-directed therapy, the ORR was 94% vs 54%, and median PFS was 16.8 vs 6.2 months in those treated ≥6 months vs <6 months from last BCMA exposure, respectively.
• CRS was reported in 75% of patients, including grade ≥3 CRS in 5% and 3 grade 5 events. The median time to onset of CRS was 7 days. ICANS was reported in 14% of patients, including grade ≥3 ICANS in 4% and 1 grade 5 event. The median time to onset of ICANS was 9 days. Delayed neurotoxicity (DNT) was reported in 24 patients (10%), including seventh cranial nerve palsy (n=11), parkinsonism (n=5), diplopia (n=4), posterior reversible encephalopathy syndrome (PRES; n=2), dysautonomia (n=1), and polyneuropathy (n=1). IEC-HS was reported in 2% of patients, and any-grade infections in 47%, with severe infections reported in 49 patients (46%). Grade ≥3 neutropenia and thrombocytopenia at day 30 were reported in 59% and 49% of patients, respectively. Grade ≥3 neutropenia was reported in 20% and 11% of patients at days 60 and 90 after CAR T-cell therapy, respectively, and grade ≥3 thrombocytopenia was reported in 22% and 14% of patients. Granulocyte colony-stimulating factor (G-CSF), thrombopoietin agonists, and stem cell rescue were used in 52%, 9%, and 5% of patients, respectively. Secondary primary malignancies (SPMs) were reported in 20 infused patients (8.5%), including 13 patients (5.5%) with SPMs other than nonmelanoma skin cancer; these included myeloid malignancies/acute leukemia (n=3), prostate cancer (n=3), T-large granular lymphocytic leukemia (n=2), colorectal cancer (n=2), peripheral T-cell lymphoma (n=1), breast cancer (n=1), and melanoma (n=1).
  • At the last follow-up, 50 patients had died, including 23 (10%) deaths attributed to NRM. Infections were the most common cause of NRM (n=12; including progressive multifocal leukoencephalopathy in 1), followed by CRS (n=3), DNT (n=3), IEC-HS (n=2), ICANS (n=1), and second primary malignancies (n=1).
• Bridging therapy administered in 78% of patients (n=184) had ORR of 27%. Fludarabine/cyclophosphamide (Flu/Cy) was used for lymphodepletion in 81% of patients; alternative regimens included bendamustine (13%), cladribine and cyclophosphamide (3%), and cyclophosphamide alone (3%).
• Patients who received an out of specification/nonconforming product were more likely to have undergone a prior autologous transplant (95% vs 82%; P=0.03), received a prior bispecific antibody (11% vs 3%; P=0.02), and had higher baseline ferritin levels (342.5 vs 187.0 ng/mL; P=0.006) and C-reactive protein levels (3.4 vs 1.9 mg/L; P=0.008) than those who received an in-specification/conforming chimeric antigen receptor (CAR) T-cell product.

Multicenter US Experience With CARVYKTI in RRMM

Sidana et al (2023)⁶ presented a multicenter study evaluating outcomes in patients treated with intended CARVYKTI at 14 US academic centers. Overall, 153 patients underwent apheresis with intention to manufacture CARVYKTI by September 15, 2022, and 143 (94%) received a CARVYKTI infusion.

• The median follow-up was 6 months.
• The median age was 64 years, with 27% of patients aged >70 years. Penta-refractory disease, high-risk cytogenetics, and EMD were reported in 34%, 41%, and 31% of patients, respectively.
• Among patients who received CARVYKTI (n=140), the partial response or better (≥PR) was 89%, with 77% achieving a ≥VGPR and 56% achieving a ≥CR. The median PFS was not reached, and the 6-month estimated PFS rate was 79%.
  • In the non-expanded access protocol (EAP) fludarabine/cyclophosphamide (Flu/Cy)-treated cohort (N=92), the ORR was 94%, with 61% of patients achieving a ≥CR.
• CRS was reported in 80% of patients, with grade ≥3 CRS reported in 5%. ICANS was reported in 18% of patients, with grade ≥3 ICANS reported in 6%. HLH-like syndrome was reported in 3% of patients. Use of tocilizumab, steroids, and anakinra was reported in 61%, 41%, and 13% of patients, respectively. DNT was reported in 17 patients (12%), comprising seventh cranial nerve palsy (n=9), Parkinsonism (n=2), and other neurologic toxicities (n=6) with a median time to onset being 25 days. DNT was resolved in 6 patients by last follow-up. Infections were reported in 37% of patients.
  • At the data cutoff, 22 patients had died; 14 (10%) deaths attributed to NRM. Infections were the most common cause of NRM (n=6), followed by grade 5 CRS (n=3), DNT (n=2), grade 5 ICANS (n=1), HLH (n=1), and combined CRS/infection (n=1).
• Bridging chemotherapy was administered to 80% of patients, with an ORR of 30%. Lymphodepletion regimens included Flu/Cy (84%), bendamustine (9%), cyclophosphamide alone (3.5%), and cladribine and cyclophosphamide (3.5%). The median CAR T-cell dose infused was 0.6 million/kg, and 22% of patients were treated under an EAP.

Association of CARVYKTI Dose With Efficacy and Safety Outcomes

Clinical Outcomes Across CARVYKTI Dose Cohorts at US Academic Centers

Reshef et al (2025)⁷ presented a multicenter retrospective analysis from the US Multiple Myeloma Immunotherapy Consortium evaluating the association between CARVYKTI dose and clinical outcomes in 751 patients with RRMM treated across 15 US academic centers.

• The median follow-up was 12.3 months (interquartile range, 6.9-20.5).
• Patients were stratified into low-dose (<0.5 million cells/kg; n=33), standard-low-dose (0.5 to <0.6 million cells/kg; n=131), standard-dose (0.6 to <0.8 million cells/kg; n=550), and standard-high-dose (0.8 to 1.0 million cells/kg; n=37) cohorts.
• Across the low-, standard-low-, standard-, and standard-high-dose cohorts, ORRs were 97%, 96%, 96%, and 88%, respectively, whereas CR rates were 75%, 65%, 75%, and 66%, respectively. Across the standard-low-, standard-, and standard-high-dose cohorts, median PFS was 17.5 months, 28.7 months, and not reached, respectively; median follow-up in the low-dose cohort was 8.7 months. The corresponding 12-month PFS rates were 62%, 67%, 73%, and 80% for the low-, standard-low-, standard-, and standard-high-dose cohorts, respectively.
• No significant differences in the rates of any grade CRS, any grade ICANS, grade ≥3 ICANS, duration of CRS, duration of ICANS, and duration of IEC-HS were observed across dose cohorts.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 07 August 2026.