SUMMARY

• Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• Outpatient administration of CARVYKTI is being explored in the CARTITUDE-2 and CARTITUDE-5 studies.^1,2
• CARTITUDE-2 (MMY2003) is a phase 2, multicohort, open-label study evaluating CARVYKTI in patients with multiple myeloma (MM) in various clinical settings.^3-6
  • Patients are assessed for suitability for outpatient administration at the time of apheresis, prior to lymphodepletion, and again prior to CARVYKTI infusion based on investigator’s discretion, patient’s willingness, institutional guidance, and sponsor’s approval.²
  • Cohort A is evaluating the efficacy and safety of CARVYKTI in 20 patients who had progressive MM after 1-3 prior lines of therapy and were refractory to lenalidomide.⁴
    • One patient was treated in an outpatient setting in Cohort A.⁴
      • Grade 2 cytokine release syndrome (CRS) occurred 9 days after CARVYKTI infusion, with a duration of 2 days; grade 2 isolated facial paralysis occurred 29 days after CARVYKTI infusion and resolved completely within 51 days of onset after treatment with dexamethasone.⁴
  • Cohort B is evaluating the efficacy and safety of CARVYKTI in 19 patients who had early relapse after initial therapy with a PI and an immunomodulatory agent.⁵
    • One patient was treated in an outpatient setting in Cohort B.⁵
• CARTITUDE-5 (MMY3004) is an ongoing phase 3, randomized, open label, multicenter, global study evaluating efficacy and safety of CARVYKTI as frontline therapy in patients with newly diagnosed multiple myeloma (NDMM) not intended for transplant.¹
  • Patients are assessed for suitability for outpatient administration based on investigator’s discretion, patient’s willingness, institutional guidance, and sponsor’s approval.¹
  • The study is currently ongoing, and results have not been published.
• Additional studies that evaluated CARVYKTI in an outpatient setting have been identified in addition to the data summarized above.^7-9
  • Select outpatient analyses have been summarized in the Clinical Data - Real-World Studies Section.  

clinical data - CARTITUDE-2 - Phase 2 Study

CARTITUDE-2 (MMY2003; clinicaltrials.gov identifier: NCT04133636) is an ongoing, phase 2, open-label, multicohort, single-arm, multicenter study evaluating the efficacy and safety of CARVYKTI in patients with MM in various clinical settings.^3-6

• Cohort A is evaluating the efficacy and safety of CARVYKTI in 20 patients who had progressive MM after 1-3 prior lines of therapy and were refractory to lenalidomide at a median follow-up of 17.1 months.⁵
• Cohort B is evaluating the efficacy and safety of CARVYKTI in 19 patients who had early relapse after initial therapy with a PI and an immunomodulatory agent at a median follow-up of 18 months.⁶

Study Design/Methods

• Key eligibility criteria for Cohort A: adult patients with progressive MM after 1-3 prior lines of therapy, including a PI and an immunomodulatory agent, who were lenalidomide refractory, had no prior exposure to B-cell maturation antigen (BCMA)-targeting agents or chimeric antigen receptor T-cell (CAR-T) therapy directed at any target, and had an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.¹⁰
• Key eligibility criteria for Cohort B: adult patients who received 1 prior lines of therapy including a PI and an immunomodulatory agent, had disease progression per International Myeloma Working Group (IMWG) criteria ≤12 months after autologous stem cell transplant (ASCT) or ≤12 months from the start of antimyeloma therapy (for patients who did not receive ASCT), had no prior exposure to BCMA-targeting agents or CAR-T therapy directed at any target, and had an ECOG performance status of ≤1.¹⁰
• Patients are assessed for suitability for outpatient administration at the time of apheresis, prior to lymphodepletion, and again prior to CARVYKTI infusion based on investigator’s discretion, patient’s willingness, institutional guidance, and sponsor’s approval.⁴
• Key clinical considerations and monitoring guidelines for outpatient administration in CARTITUDE-2 are described in the Table: CARTITUDE-2 Outpatient Administration Guidelines.
• Dosing: patients received a single infusion of CARVYKTI at a target dose of 0.75x10⁶ viable CAR+ T cells/kg (target range, 0.5-1.0x10⁶) 5-7 days after the start of lymphodepletion/conditioning regimen (cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily for 3 days on days -5 to -3).^3-6
• Primary endpoint: percentage of patients with minimal residual disease (MRD) negativity at the 10^-5 sensitivity level defined by IMWG criteria (assessed by next-generation sequencing; clonoSEQ^®).^3-6
• Secondary endpoints: Overall response rate per the IMWG response criteria, duration of response (DOR), time and duration of MRD-negativity, and incidence and severity of adverse events (AEs).^3-6

Results

• Cohort A: A total of 20 patients were treated in Cohort A; 1 patient was treated in an outpatient setting.⁴
  • Grade 2 CRS event occurred 9 days after infusion, with a duration of 2 days.⁴
  • Grade 2 isolated facial paralysis occurred 29 days after CARVYKTI infusion and resolved completely within 51 days of onset after treatment with dexamethasone.⁴
  • Response rates specific to this patient have not been published.⁴
• Cohort B: A total of 19 patients were treated in Cohort B; 1 patient was treated in an outpatient setting.³
  • Response rates specific to this patient have not been published.³

clinical data - CARTITUDE-5 - Phase 3 Study

CARTITUDE-5 (MMY3004; clinicaltrials.gov identifier: NCT04923893) is an ongoing, phase 3, randomized, open label, multicenter, global study evaluating efficacy and safety of CARVYKTI as frontline therapy in patients with NDMM, for whom ASCT is not planned as initial therapy. In this study, the efficacy of induction treatment with bortezomib, lenalidomide, and dexamethasone (VRd) followed by single infusion of CARVYKTI will be compared with induction treatment with VRd followed by maintenance treatment with lenalidomide and dexamethasone (Rd).¹

Study Design/Methods

• Key eligibility criteria: adult patients with NDMM per IMWG criteria, measurable disease, ECOG performance status ≤1; ineligible for high dose chemotherapy with ASCT due to advanced age, comorbid conditions or deferment of ASCT.¹
• Patients are assessed for suitability for outpatient administration based on investigator’s discretion, patient’s willingness, institutional guidance, and sponsor’s approval.¹
• Key clinical considerations and monitoring guidelines for outpatient administration in CARTITUDE-5 are described in the Table: CARTITUDE-5 Outpatient Administration Guidelines.
• Primary endpoint: progression-free survival (PFS) defined by IMWG criteria, or death, whichever occurs first.¹
• Secondary endpoints: sustained MRD-negative complete response, overall MRD-negativity rate, overall survival (OS), complete response or better (≥CR), time to subsequent anti-myeloma therapy, and PFS on next-line therapy, incidence and severity of AEs, pharmacokinetics and pharmacodynamics, patient reported outcomes.¹

Results

• The study is currently ongoing, and results have not been published.

CLINICAL DATA - REAL-WORLD STUDIES

Waqar et al (2024)⁷ conducted a single-center, retrospective study evaluating the outpatient administration of CARVYKTI in patients with relapsed/refractory multiple myeloma (RRMM) through an established dedicated outpatient cellular therapy service, Immune Cell Therapy (ICE T), at the Moffitt Cancer Center (MCC).

Study Design/Methods

• The study was conducted at MCC between May 2022 and May 2023, with a focus on the first 30 days after CARVYKTI infusion in patients with RRMM.⁷
• Initially, patients received lymphodepleting chemotherapy as outpatient; then received CAR-T infusion and underwent monitoring as inpatient and were later discharged to the outpatient ICE T service.⁷
• Thereafter, the practice was modified to provide lymphodepleting chemotherapy, CARVYKTI infusion, and monitoring in the outpatient setting. Patients were admitted as inpatient as per clinical needs.⁷
• Patients were monitored and assessed for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) through day +30 after infusion.⁷

Results

• A total of 43 patients with RRMM were included in this analysis. The inpatient group included 6 patients (14.0%), the scheduled outpatient to inpatient group included 10 patients (23.3%) and the outpatient group included 27 patients (62.8%).⁷ Baseline characteristics of these patients are presented in Table: Baseline Characteristics of CARVYKTI-Treated Patients.

Efficacy

• OS and PFS rates were similar across the administration types. At a median follow-up of 7.7 months (range, 2.9-14.4), the 1-year OS was 96.3% (95% confidence interval [CI], 76.5-99.5; P=0.068) and the 1-year PFS was 85.8% (95% CI, 60.6-95.5; P=0.10) for the surviving patients from the outpatient group.⁷

Safety

• The median hospitalization duration for the inpatient group was 19 days (range, 9-36).⁷
  • Patients from the inpatient group were hospitalized for MM-related conditions (n=4), chemotherapy-related gastrointestinal toxicity (n=1), and patient preference (n=1).
• A total of 25 patients (92.6%) from the outpatient group were admitted after CARVYKTI infusion. The median hospitalization duration was 4 days (range, 1-33).⁷
  • Of these, 22 patients (81.5%) were primarily hospitalized for CRS and 5 patients were hospitalized for clinical indications (arrhythmia, infection, and social reasons).
  • Three patients (11.1%) who underwent outpatient ICE T, required a second hospital admission within 30 days of CARVYKTI infusion (2 for ICANS and 1 for infection).
• All patients from the scheduled outpatient to inpatient group were admitted on day -1 as planned with a median hospitalization duration of 11 days.⁷

Ly et al (2024)⁸ conducted a retrospective study on the safety and feasibility of CARVYKTI administration in an outpatient setting.

Study Design/Methods

• The study included patients who received CARVYKTI in an outpatient setting, with a data cutoff date of October 1, 2023.⁸
• CRS, ICANS, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) were graded as per American Society for Transplantation and Cellular Therapy (ASTCT) 2019 and 2023 criteria, and responses were graded using standard criteria.⁸
• Patients received outpatient lymphodepletion chemotherapy and outpatient CARVYKTI infusion; daily monitoring was conducted for 14 days in the extended hour outpatient unit.⁸
• The first patient was preemptively admitted after CARVYKTI infusion to monitor CARVYKTI safety before instituting the full outpatient paradigm.⁸

Results

• A total of 14 patients received CARVYKTI in an outpatient setting, of which 1 patient had nervous system involvement.⁸ Baseline characteristics of these patients are presented in Table: Baseline Characteristics of Outpatient CARVYKTI Patients.
• The median follow-up was 99.5 days (range, 13-282).⁸

Efficacy

Response

• Eleven patients were evaluable for ≥1 response assessment; of these, 5 patients (45%) showed ≥CR.⁸ The response rates in patients who received CARVYKTI is presented in Table: Response Rates in Evaluable CARVYKTI-Treated Patients.

Safety

• A summary of safety outcomes are presented in Table: Summary of Safety Outcomes.
• A total of 11 patients (79%) were admitted for toxicity management, with 4 patients being admitted within 72 hours of infusion.⁸
• CRS was reported in 12 patients (86%), with 50% of events being grade 1 and 2.⁸
  • Patients received either tocilizumab (n=10) or anakinra (n=2).
  • One patient with grade 1 CRS was managed through close outpatient monitoring; another patient with grade 1 CRS was hospitalized for 2 days but did not require any therapeutic intervention.
• ICANS was reported in 4 patients (29%), with 50% of events being grade 1 and 2.⁸
  • Patients received either steroids (n=3) or anakinra (n=1).
  • Facial paralysis was reported in 1 patient on day 16, which improved with dexamethasone and anakinra but with residual jaw numbness.
  • Parkinsonism secondary to CAR-T was reported in 1 patient on day 50, which resolved with a 4-day course of dexamethasone.
• IEC-HS was reported in 2 patients (grade 1 and 2).⁸
  • Anakinra was used to treat grade 1 IEC-HS, and anakinra and ruxolitinib were used to treat grade 2 IEC-HS.
• Of the 12 patients with a ≥30-day follow-up, 67% had absolute neutrophil count (ANC) >500/μl and platelet count >20,000/μl at day 30 without transfusion in the previous week. However, 2 patients remained transfusion dependent at the data cutoff date of October 1, 2023.⁸

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 07 March 2025.