SUMMARY  

• CARVYKTI is not approved by the regulatory agencies for use in newly diagnosed multiple myeloma (NDMM). Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• CARTITUDE-5 is a phase 3, randomized, open-label, multicenter, global study evaluating efficacy and safety of CARVYKTI as frontline therapy in patients with NDMM not intended for transplant. The study is currently ongoing, and results have not been published.^1,2

CLINICAL DATA

CARTITUDE-5 (MMY3004; clinicaltrials.gov identifier: NCT04923893) is a phase 3, randomized, open-label, multicenter, global study evaluating efficacy and safety of CARVYKTI as frontline therapy in patients with NDMM, for whom autologous stem cell transplant (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).^1,2

Study Design/Methods

• The study design is shown in Figure: CARTITUDE-5 Study Design.
• All patients will complete 6 cycles (21 days each) of VRd induction therapy prior to randomization, which include^1,2:
  • Bortezomib: 1.3 mg/m² subcutaneously (SC) on days 1, 4, 8, and 11
  • Lenalidomide: 25 mg orally on days 1 to 14
  • Dexamethasone: 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12
  • Participants who received 1 cycle of VRd prior to screening will only receive 5 cycles of VRd between screening and randomization.
• Following induction therapy, patients will be randomized 1:1 into one of two arms to receive the following treatments^1,2:
  • VRd + Rd arm (standard of care):
    • Patients will receive 2 additional cycles of VRd (same dose and regimen as induction cycles).^1,2
    • Rd maintenance therapy continues until progressive disease (PD) or unacceptable toxicity. 28-day maintenance cycles include^1,2:
      • Lenalidomide: 25 mg orally on days 1 to 21
      • Dexamethasone: 40 mg orally on days 1, 8, 15, and 22
  • VRd + CARVYKTI arm:
    • Patients will undergo apheresis to acquire peripheral blood mononuclear cells for CARVYKTI production. Within 7 days, patients will receive 2 more cycles of VRd as bridging therapy (same dose and regimen as initial 6 cycles).^1,2
      • After successful manufacture of CARVYKTI, patients will undergo lymphodepletion daily for 3 days with cyclophosphamide 300 mg/m² and
        fludarabine 30 mg/m².^1,2
      • CARVYKTI will be given as a single infusion on day 1 at a target dose of
        0.75×10⁶ CAR+ T cells/kg (5-7 days after the start of lymphodepletion).^1,2
• Patients will be stratified at randomization by the following factors¹:
  • Revised International Staging System (R-ISS) (I, II, III); age/transplant eligibility (≥70 years or <70 years and ASCT ineligible due to comorbidities or age <70 years and ASCT deferred); response to VRd induction (very good partial response or better [≥VGPR], partial response [≤PR]).
• 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 for outpatient administration include¹:
  • No requirement for daily packed red blood cell or platelet infusions
  • No presence of an indwelling central line
  • No fever or active infection since study enrollment
  • No grade ≥3 nonhematologic toxicities associated with lymphodepletion
  • No significant factors for bleeding in the setting of cytopenia and clinically significant tumor lysis syndrome requiring management
  • No high tumor burden defined as ≥60% plasma cell infiltration of the marrow and/or presence of extramedullary disease
  • No deterioration in neurologic status, including mental status changes (except for diphenhydramine-related confusion/somnolence that has resolved)
  • No rapidly progressing disease
  • Estimated glomerular filtration rate of ≥40 mL/min/1.73m²
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 times upper limit of normal
• Key monitoring guidelines for outpatient administration include¹:
  • Days 1-4
    • Patients must stay within 30 minutes of the hospital
    • Daily follow-up calls
    • Hospital admission is required in the event of any presenting signs and symptoms of cytokine release syndrome (CRS) and/or neurotoxicity
  • Days 5-14
    • Required inpatient admission
    • Option for discharge on day 10 in the absence of CRS, neurotoxicity, or other significant AEs
    • Daily follow-up calls through day 14.

Results

• Study results have not been published.

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 18 November 2024.