SUMMARY

• CARTITUDE-1 (MMY2001) was a phase 1b/2, open-label, single-arm, multicenter study evaluating ciltacabtagene autoleucel (cilta-cel) in patients with relapsed/refractory multiple myeloma (RRMM) who had previously received a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-cluster of differentiation (CD) 38 monoclonal antibody.^1,2
  • Based on the safety profile observed in CARTITUDE-1, outpatient dosing is being evaluated in additional CARTITUDE studies. No patients in CARTITUDE-1 were treated outpatient.¹
• Outpatient administration of cilta-cel is being explored in the CARTITUDE-2 and CARTITUDE-5 studies.^3,4
• CARTITUDE-2 (MMY2003) is a phase 2, multicohort, open-label study evaluating ciltacel in patients with multiple myeloma (MM) in various clinical settings.^5-8 CARVYKTI is not approved by the regulatory agencies for use in early relapse MM or progressive MM after 1-3 prior lines of therapy. Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
  • Patients are assessed for suitability for outpatient administration at the time of apheresis, prior to lymphodepletion, and again prior to cilta-cel infusion based on investigator’s discretion, patient’s willingness, institutional guidance, and sponsor’s approval.⁴
  • Cohort A is evaluating the efficacy and safety of cilta-cel in 20 patients who had progressive MM after 1-3 prior lines of therapy and were refractory to lenalidomide.⁶
    • One patient was treated in an outpatient setting in Cohort A.⁶
      • Grade 2 cytokine release syndrome (CRS) occurred 9 days after cilta-cel infusion, with a duration of 2 days; grade 2 isolated facial paralysis occurred 29 days after cilta-cel infusion and resolved completely within 51 days of onset after treatment with dexamethasone.⁶
  • Cohort B is evaluating the efficacy and safety of cilta-cel 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 cilta-cel as frontline therapy in patients with newly diagnosed multiple myeloma (NDMM) not intended for transplant.³ CARVYKTI is not approved by the regulatory agencies for use in NDMM. Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
  • Patients are assessed for suitability for outpatient administration based on investigator’s discretion, patient’s willingness, institutional guidance, and sponsor’s approval.³
  • The study is currently ongoing, and results have not been published.
• Waqar et al (2024)⁹ conducted a single-center, retrospective study evaluating the outpatient administration of cilta-cel in patients with RRMM by establishing a dedicated outpatient cellular therapy service, immune cell therapy (ICE T), at Moffitt Cancer Center (MCC) between May 2022 and May 2023. A total of 43 patients with RRMM were included. Ten patients (23.3%) were scheduled outpatient to inpatient, 6 patients (14.0%) were inpatient, and 27 patients (62.8%) were entirely outpatient.
  • At a median follow-up of 7.7 months (range, 2.914.4), the 1-year overall survival (OS) was 96.3% (95% confidence interval [CI], 76.599.5; P=0.068) and the 1-year progression-free survival (PFS) was 85.8% (95% CI, 60.695.5; P=0.10) in the outpatient group.
  • Out of the 27 patients in the outpatient group, 25 patients (92.6%) were hospitalized after CAR-T infusion. Out of the patients who were admitted, 22 patients (81.5%) were primarily hospitalized for CRS and 5 patients for clinical indications (arrhythmia, infection, and social reason) with the median duration of hospitalization of 4 days (range, 133).
    • A total of 3 patients (11.1%) who underwent outpatient ICE T required a second hospital admission within 30 days of CAR-T infusion (2 for immune effector cellassociated neurotoxicity syndrome [ICANS] and 1 for infection).
• Ly et al (2024)¹⁰ conducted a retrospective study (n=24) on the safety and feasibility of cilta-cel administration in an outpatient setting. The study was conducted at Johns Hopkins University from December 2022 to December 2023.
  • At a median follow-up of 138.5 days (range, 36-396), the overall response rate (ORR) was 95% in 21 efficacy-evaluable patients. Stringent complete response (sCR) was achieved in 9 (43%) patients, respectively. For more information, please refer to Table: Response Rates in Evaluable Patients.¹⁰
  • CRS was reported in 19 patients, of whom, 18 patients (75%) experienced grades 12 CRS and 1 patient (4%) experienced grades 3-4 CRS. Grade 1-2 ICANS was reported in 2 patients (8%). Movement and neurocognitive toxicity (MNT) were reported in 5 patients, of whom, 2 patients (10%) experienced grades 1-2 MNT and 3 patients experienced grades 3-4 MNT. Grade 1 and 2 immune effector cell-associated hemophagocytic lymphohistiocytosislike syndrome (IEC-HS) was reported in 2 patients.

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 cilta-cel in patients with MM in various clinical settings.^5-8

• Cohort A is evaluating the efficacy and safety of cilta-cel 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.⁷
• Cohort B is evaluating the efficacy and safety of cilta-cel 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.⁸

Study Design/Methods

• Key eligibility criteria for Cohort A: adult patients with progressive MM after 13 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 (CAR)-T cell therapy directed at any target, and had an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.¹¹
• 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 BCMAtargeting agents or CAR-T cell therapy directed at any target, and had an ECOG performance status of ≤1.¹¹
• Patients are assessed for suitability for outpatient administration at the time of apheresis, prior to lymphodepletion, and again prior to cilta-cel 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.⁴
• Dosing: patients received a single infusion of cilta-cel 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).^5-8
• Primary endpoint: percentage of patients with minimal residual disease (MRD) negativity at the 10^-5 sensitivity level defined by IMWG criteria (assessed by nextgeneration sequencing; clonoSEQ^®).^5-8
• Secondary endpoints: ORR per the IMWG response criteria, duration of response (DOR), time and duration of MRD-negativity, and incidence and severity of adverse events (AEs).^5-8

Results

• Cohort A: A total of 20 patients were treated in Cohort A; 1 patient was treated in an outpatient setting.⁶
  • Grade 2 CRS event occurred 9 days after infusion, with a duration of 2 days.⁶
  • Grade 2 isolated facial paralysis occurred 29 days after cilta-cel infusion and resolved completely within 51 days of onset after treatment with dexamethasone.⁶
  • Response rates specific to this patient have not been published.⁶
• Cohort B: A total of 19 patients were treated in Cohort B; 1 patient was treated in an outpatient setting.⁵
  • Response rates specific to this patient have not been published.⁵

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 cilta-cel 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 cilta-cel will be compared with induction treatment with VRd followed by maintenance treatment with lenalidomide and dexamethasone (Rd).³

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.³
• Patients are assessed for suitability for outpatient administration based on investigator’s discretion, patient’s willingness, institutional guidance, and sponsor’s approval.³
• Key clinical considerations and monitoring guidelines for outpatient administration in CARTITUDE-5 are described in the Table: CARTITUDE-5 Outpatient Administration Guidelines.³
• Primary endpoint: PFS defined by IMWG criteria, or death, whichever occurs first.³
• Secondary endpoints: sustained MRD-negative CR, overall MRD-negativity rate, OS, CR or better, time to subsequent anti-myeloma therapy, and PFS on next-line therapy, incidence and severity of AEs, pharmacokinetics and pharmacodynamics, patient reported outcomes.³

Results

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

CLINICAL DATA – REAL-WORLD STUDIES

Waqar et al (2024)⁹ conducted a single-center, retrospective study evaluating the outpatient administration of cilta-cel in patients with RRMM by establishing a dedicated outpatient cellular therapy service, ICE T, at MCC between May 2022 and May 2023.

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 delivery in RRMM patients.⁹
• Initially, patients received lymphodepleting chemotherapy as outpatients and then CART infusion and monitoring as inpatients, followed by discharge to outpatient ICE T service.⁹
• Thereafter, the practice was modified to provide lymphodepleting chemotherapy, CAR-T infusion, and monitoring as outpatients. Patients were admitted as inpatients as per clinical needs.⁹
• Patients were monitored through day +30 after infusion for CRS and ICANS.⁹

Results

• A total of 43 patients with RRMM were included in either the inpatient group (n=6, 14%), the outpatient group (n=27, 62.8%), or the scheduled outpatient to inpatient group (n=10, 23.3%). The baseline characteristics of patients is presented in the Table: Baseline Characteristics of Cilta-Cel treated Patients.⁹

Efficacy

• At a median follow-up of 7.7 months (range, 2.9-14.4), the 1year OS was 96.3% (95% CI, 76.5-99.5; P=0.068) and 1-year PFS was 85.8% (95% CI, 60.695.5; P=0.10) in the outpatient group.⁹

Safety

• The median value of maximum CRS grade was 4 (range, 1-5) for inpatients, 1 (range, 0-2) for outpatients, and 1 (range, 0-2) for scheduled outpatients to inpatients.⁹
• The median value of maximum ICANS grade was 0 (range, 0-2) for inpatients, 0 (range, 0-3) for outpatients, and 0 (range, 0-0) for scheduled outpatients to inpatients.⁹
• The median number of days of hospital admission was 19 days (range, 9-36) for inpatients, 4 days (range, 0-33) for outpatients, and 11 days (range, 4-69) for scheduled outpatients to inpatients.⁹
• Out of the 27 patients in the outpatient group, 25 (92.6%) were hospitalized after CART infusion primarily for CRS (81.5%). The median duration of hospitalization was 4 days (range, 1-33).⁹
  • A second admission (2 for ICANS and 1 for infection) within 30 days of CAR-T infusion was required by 3 (11.1%) outpatients in ICE T.⁹

Ly et al (2024)¹⁰ presented a retrospective study on the safety and feasibility of cilta-cel administration in an outpatient setting.

Study Design/Methods

• The study included patients (n=24) who received cilta-cel at Johns Hopkins University from December 2022 to December 2023 in an outpatient setting.¹⁰
• The primary outcomes were incidence, severity, and duration of CRS, ICANS, and MNT.¹⁰
• The secondary outcomes were hospitalization and intensive care unit (ICU) admission, hematopoietic recovery, transfusions, infections, and response.¹⁰
• Responses were defined using the IMWG criteria.¹⁰
• CRS, ICANS, and IEC-HS were graded as per the ASTCT criteria.¹⁰
• MNT was graded using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).¹⁰

Results

• A total of 24 patients (median age, 59 years [range, 38-79]) received CARVYKTI in an outpatient setting. The baseline characteristics of outpatients is presented in the Table: Baseline Characteristics of Outpatients.¹⁰
• The patients received 8 (range, 4-15) prior lines of treatment.¹⁰
• The median follow-up was 138.5 days (range, 36-396).¹⁰

Efficacy

Response

• There were 21 efficacy-evaluable patients, and the ORR was 95% (n=20) in these patients. The response rates of patients who received cilta-cel is presented in Table: Response Rates in Efficacy-Evaluable Patients.¹⁰

Safety

• The toxicity outcomes are presented in the Table: Toxicity Outcomes.¹⁰
• CRS was reported in 19 patients, of whom 18 (75%) and 1 (4%) reported grades 1-2 and 3-4 CRS, respectively.¹⁰
• Grade 1 CRS was managed in 1 patient by outpatient monitoring; another patient with grade 1 CRS who was hospitalized for 2 days did not require any therapeutic intervention.¹⁰
• Grade 1-2 ICANS were reported in 2 (8%) patients.¹⁰
• MNT was reported in 5 patients, of whom 2 (8%) and 3 (13%) experienced grades 2 and 3 MNT, respectively. MNT and associated treatment are presented in Table: MNT Symptoms and Management.¹⁰
• Grade 1-2 IEC-HS was reported in 2 patients.¹⁰
  • Anakinra was used to treat grade 1 IEC-HS, and anakinra and ruxolitinib were used to treat grade 2 IEC-HS.¹⁰

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 05 March 2024.