SUMMARY

• CARVYKTI is a B-cell maturation antigen (BCMA)directed, genetically modified, autologous T cell immunotherapy, which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells expressing BCMA.¹
• CARVYKTI is prepared from the patient’s peripheral blood mononuclear cells that are enriched for T cells and genetically modified ex vivo by transduction to express a CAR.¹
• The transduced anti-BCMA CAR T cells are expanded in cell culture, washed, formulated into a suspension, and cryopreserved. The product must pass a sterility test before release for shipping as a frozen suspension in a patient-specific infusion bag.¹
• CARTITUDE-1 (MMY2001) was a phase 1b/2, open-label, single-arm, multicenter study that evaluated CARVYKTI in patients with relapsed/refractory multiple myeloma (RRMM) who had previously received a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-cluster of differentiation 38 (CD38) monoclonal antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the safety and efficacy of CARVYKTI in 97 patients with RRMM.^1-3
  • Of the 97 efficacy-evaluable patients in CARTITUDE-1, manufacturing failure occurred in 17 patients (18%) because they received CARVYKTI that did not meet product release specifications for CARVYKTI or received CARVYKTI for which there were insufficient data to confirm product release specifications for CARVYKTI.¹
  • The median time from leukapheresis to product availability was 32 days (range, 27-66).¹
  • No patient discontinued because of manufacturing failure.^2,3
• CARTITUDE-4 (MMY3002) is an ongoing phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO^® [daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in adult patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior line(s) of therapy (LOT).^4,5
  • Overall, 419 patients were randomized to receive CARVYKTI (n=208) or standard care (n=211; DPd [n=183] or PVd [n=28]).⁴
    • All 208 patients randomized to the CARVYKTI arm underwent apheresis followed by ≥1 bridging therapy cycle with either DPd (n=182) or PVd (n=26); with the number of cycles based on clinical status and CARVYKTI manufacturing time. A total of 176 patients (84.6%) received CARVYKTI as study treatment (as-treated population).^1,4
  • In the 176 patients that received CARVYKTI as study treatment, the median time from the day after receipt of apheresis material at manufacturing facility to release of product for infusion was 44 days (range, 25-127 days) and the median time from first apheresis to CARVYKTI infusion was 79 days (range, 45-246 days).^1,4,6
  • No patient discontinued treatment because of manufacturing failure.⁴

PRODUCT LABELING

Prescribing Information

• CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf.  
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.

Description

• CARVYKTI is a BCMA-directed, genetically modified, autologous T cell immunotherapy. CARVYKTI is prepared from the patient’s peripheral blood mononuclear cells, which are obtained via a standard leukapheresis procedure.¹
• The mononuclear cells are enriched for T cells and genetically modified ex vivo by transduction with a replication-incompetent lentiviral vector to express a CAR comprising an anti-BCMA targeting domain, which consists of 2 single-domain antibodies linked to a 4-1BB costimulatory domain and a CD3zeta signaling domain.¹
• The transduced anti-BCMA CAR T cells are expanded in cell culture, washed, formulated into a suspension, and cryopreserved. The product must pass a sterility test before release for shipping as a frozen suspension in a patient-specific infusion bag.¹
• The product is thawed and then infused back into the patient, where the anti-BCMA CAR T cells can recognize and eliminate BCMA-expressing target cells.¹
  • In addition to T cells, CARVYKTI may contain Natural Killer (NK) cells. The formulation contains 5% dimethyl sulfoxide (DMSO).¹

Clinical Studies

CARTITUDE-1

• The efficacy of CARVYKTI was evaluated in CARTITUDE-1. Of the 113 patients who underwent leukapheresis, 16 patients did not receive CARVYKTI due to progressive disease (n=2), death (n=9), or withdrawal from study (n=5).¹
• There were 97 patients in the efficacy-evaluable population who received CARVYKTI, including 17 patients (18%) with manufacturing failures because they either¹:
  • received CARVYKTI that did not meet product release specifications for CARVYKTI or,
  • received CARVYKTI for which there were insufficient data to confirm product release specifications for CARVYKTI.
• The median time from leukapheresis to product availability was 32 days (range, 2766 days).¹
• In case of a manufacturing failure, a second manufacturing of CARVYKTI may be attempted.¹

CARTITUDE-4

• The efficacy of CARVYKTI was evaluated in CARTITUDE-4. All 208 patients randomized to the CARVYKTI arm underwent apheresis, of whom 12 (6%) were not treated with CARVYKTI due to progressive disease (n=10) or death (n=2), and 20 (10%) progressed prior to infusion with CARVYKTI but were able to receive CARVYKTI as subsequent therapy. Eight (4%) patients received CAR T positive T cells that did not meet product release specification for CARVYKTI (non-conforming product).¹
  • The apheresis was followed by at least 1 bridging therapy cycle with either DPd (n=182) or PVd (n=26), with the number of cycles based on clinical status and CARVYKTI manufacturing time. A total of 176 patients (84.6%) received CARVYKTI as study treatment.^1,4
  • In the 176 patients that received CARVYKTI as study treatment, the median time from the day after receipt of apheresis material at manufacturing facility to release of product for infusion was 44 days (range, 25-127 days) and the median time from first apheresis to CARVYKTI infusion was 79 days (range, 45-246 days).^1,4,6

Literature search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 15 April 2024.