SUMMARY

• Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• Richardson et al (2025)¹ conducted a multicenter retrospective study that evaluated the safety and feasibility of sequential treatment with CARVYKTI in 10 heavily pretreated patients with relapsed refractory multiple myeloma (RRMM) who progressed after treatment with idecabtagene vicleucel (ide-cel).
• Mobascher et al (2025)² presented a case report of a 59-year-old patient with RRMM who received CARVYKTI after achieving a partial but not durable remission with ide-cel.
• Pan et al (2025)³ reported a case report of a male patient in his late 50s with RRMM who was initially treated with ide-cel with progressive disease (PD) and subsequently treated with CARVYKTI to achieve complete response (CR).
• Attar et al (2023)⁴ presented a case series of 5 patients with RRMM and evaluated the response and toxicity profile following second chimeric antigen receptor (CAR) T-cell therapy with CARVYKTI upon relapse after initial treatment with ide-cel.

PRODUCT LABELING

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

CLINICAL DATA

Richardson et al (2025)¹ conducted a multicenter retrospective study to evaluate the safety and feasibility of sequential treatment with CARVYKTI in 10 heavily pretreated patients with RRMM who progressed after treatment with ide-cel.

Study Design/Methods

• The study was conducted at 3 tertiary CAR T-cell therapy centers in Germany between April 2021 and December 2024.
• All patients were treated in-label with ide-cel as the first B-cell maturation antigen (BCMA) CAR T-cell therapy product.
  • The sequence of ide-cel followed by CARVYKTI was based on approval timelines and availability.
  • One patient was excluded due to failure to collect T cells prior to CARVYKTI therapy.
• The decision to administer CARVYKTI was based on individual patient characteristics, disease status and was at the physician’s discretion.
• Leukapheresis was performed at disease progression after last therapy.
  • TALVEY was paused ≥3 weeks before leukapheresis to protect T-cell fitness.
• Bridging therapy between apheresis and CAR T-cell infusion was allowed.
• Assessment and evaluation criteria:
  • BCMA expression was confirmed using immunohistochemistry or flow cytometry.
  • Minimal residual disease (MRD) was assessed in bone marrow with sensitivity <10⁻⁵.
  • CAR T-cell expansion was measured using real-time polymerase chain reaction or flow cytometry.
  • Response evaluation followed the International Myeloma Working Group (IMWG) criteria.
  • High-risk cytogenetics were defined per IMWG consensus.
• Patients receiving CARVYKTI were stratified by ide-cel response duration (≤12 or ≥12 months).
• The overall response rate (ORR) and progression-free survival (PFS) were evaluated.

Results

Patient Characteristics

• A total of 10 patients refractory to conventional therapies and heavily pretreated with a median of 7 (range, 5-12) prior lines of therapy (LOTs) were included in the study.
  • Baseline characteristics of patients at CARVYKTI infusion are summarized in Table: Baseline Characteristics of Treated Patients.

Efficacy

• Best overall response following ide-cel and subsequent CARVYKTI treatment is summarized in Table: Best Overall Response and PFS for ide-cel and CARVYKTI.
• After CARVYKTI infusion, at a median follow-up of 8.8 months, median PFS and overall survival were not reached.
  • Three patients relapsed after CARVYKTI infusion, resulting in a 6-month PFS of 64.8% (95% confidence interval, 39%-100%).
  • Among patients with PD, 3 out of 4 patients relapsed prior to CARVYKTI infusion.
  • All 6 patients remained MRD-negative at last follow-up.
• Patients with shorter PFS following ide-cel therapy (≤12 months) experienced significantly worse outcomes after CARVYKTI infusion and all such patients relapsed within 6 months, whereas patients with longer PFS following ide-cel therapy (>12 months) had a more durable response after CARVYKTI infusion (P=0.0024).

Safety

• No severe cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) was reported after either infusion.
• Hospitalization due to infections occurred in 5 patients following ide-cel and 3 patients following CARVYKTI treatment.
• After CARVYKTI infusion, 1 patient required autologous bone marrow transplantation due to grade 3 late immune effector cell–associated hematotoxicity with subsequent hematologic recovery.
• Movement or neurocognitive treatment-emergent adverse events were not observed.
• One patient developed trochlear palsy after CARVYKTI treatment.
• No treatment-related deaths were reported.

Mobascher et al (2025)² reported a case of a 59-year-old patient with RRMM who received CARVYKTI after achieving a partial but not durable remission with ide-cel.

Results

Patient Characteristics and Treatments Received

• A 59-year-old patient was initially diagnosed with lambda light chain (LC) multiple myeloma (MM), and International Staging System (ISS) 1 and revised (R)-ISS 2 with highrisk cytogenetics (+1q,del[13q14]).
• Patient history is summarized by LOT, including treatment modifications, responses, and disease progression in Table: Summary of Treatment History by the LOT.
• The patient was recommended CARVYKTI as seventh-LT after lymphodepletion with fludarabine (Flu)/cyclophosphamide (Cy).

Efficacy

• As of February 2025, 13 months post CARVYKTI infusion, the patient achieved stringent CR (sCR) with unmeasurable LCs, negative immunofixation in serum and urine, no malignant plasma cells in the bone marrow, and regression of metabolic activity of the large scapula lesion.

Safety

• After CARVYKTI infusion, the patient developed grade 2 CRS that quickly improved with tocilizumab administration.
• No ICANS was reported.
• CAR T-cells persisted for 10 months with peak expansion on day (D)14 with 2704/μL of BCMACAR T-cells.
• Complete depletion of B-cells and ongoing cytopenia without the need for growth factor support (grade 2-3 thrombocytopenia, grade 1 neutropenia and anemia).

Pan et al (2025)³ reported a case of a male patient in his late 50s with RRMM who was initially treated with ide-cel with PD and subsequently treated with CARVYKTI to achieve CR.

Study Design/Methods

• Longitudinal single-cell multimodal analyses (paired RNA-seq/CITE-seq/TCR-seq) of patients’ CAR T-cell infusion products, post-infusion peripheral blood mononuclear cells, and post-infusion bone marrow biopsies.

Results

Patient Characteristics and Treatments Received

• The patient was in his late 50s with immunoglobulin G-lambda myeloma and high-risk cytogenetics. At diagnosis, he received VRd followed by tandem ASCT and lenalidomide maintenance.
• The patient achieved MRD-negative CR before eventual relapse and then received DKd, but relapsed in less than a year.
• The patient was subsequently administered ide-cel with lymphodepletion with Flu/Cy.
• Disease progression was noted following ide-cel with new hypermetabolic tumor activity in his bilateral humeri.
• Following holding therapy with pomalidomide and dexamethasone, the patient received CARVYKTI with lymphodepletion with bendamustine (due to fludarabine shortage).

Efficacy

• No response was achieved after ide-cel treatment.
• MRD-negativity (10^-6 sensitivity) with CR was achieved after CARVYKTI treatment, with a significant reduction of hypermetabolic lesions in his bilateral humeri and no evidence of new lesions.

Safety

• Grade 2 CRS was reported after ide-cel treatment, and the patient received 1 dose of tocilizumab.
• After treatment with CARVYKTI, grade 1 CRS and immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome were reported, for which he received tocilizumab and dexamethasone.

Longitudinal Single-cell Analysis

• The ide-cel infusion product was cluster of differentiation (CD)4+dominant (15% CD8+ and 85% CD4+), whereas the CARVYKTI infusion product had a more balanced ratio of CD8+ and CD4+ CAR-T cells (58% CD8+ and 42% CD4+).
• Ide-cel peak expansion occurred on D9, whereas CARVYKTI peak expansion occurred on D14.
  • Despite the consistent presence of T cells, ide-cel was detected minimally at both peak and post-peak timepoints (D12, D21, D28), whereas CARVYKTI was easily detected and lasted through D21 and D28 in the peripheral blood.
  • Effective infiltration in the bone marrow was detected for CARVYKTI than for ide-cel.
• CARVYKTI infusion generated CAR T-cells that resembled T resident memory (TRM) lineage.
• Post CARVYKTI infusion, CD8+ CAR T-cells continued to exhibit CAR-TRM traits.
• CARVYKTI eliminated persistent tumor and reversed bone marrow inflammation caused by ide-cel.
• The loss of natural killer cell cytotoxicity by ide-cel was recovered through CARVYKTI infusion.

Attar et al (2023)⁴ presented a case series of 5 patients with RRMM and evaluated the response and toxicity profile following second CAR T-cell therapy with CARVYKTI upon relapse after initial treatment with ide-cel.

Results

Patient Characteristics

• A total of 5 patients were included in the study. The baseline characteristics of patients are presented in Table: Baseline Patient Characteristics.
• All patients received CARVYKTI at the time of subsequent relapse after first CAR T-cell therapy with ide-cel.

Efficacy

• After first CAR T-cell therapy with ide-cel, the ORR was 80%, with 4 patients achieving ≥VGPR (VGPR, n=2; sCR, n=2) and 1 patient with refractory disease.
  • The median duration of response for responders was 16 months (range, 7-22), and median PFS was 10 months.
• Time between 2 CAR T-cell therapies ranged from 8-38 months, with all patients receiving at least 1 and up to 2 LOTs, including bridging therapy prior to treatment with CARVYKTI.
• After the second CAR T-cell therapy with CARVYKTI, the follow-up period was 3.1-11 months.
  • Four out of 5 patients achieved a response (CR, n=3; PR, n=1), with a 6-month PFS of 75%.
  • One patient was refractory and needed subsequent treatment. The same patient was also refractory to ide-cel.

Safety

• Grade 2 CRS was reported in 1 patient after CARVYKTI treatment.
• Hematologic toxicities reported in all patients were grade 3-4 neutropenia (n=5), grade 3 anemia (n=3), and grade 4 thrombocytopenia (n=2).
• One patient reported with prolonged grade 3-4 thrombocytopenia and required transfusions and thrombopoietin analogs.

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 17 November 2025.