Source: Myeloma – Hematology Advisor
The Food and Drug Administration (FDA) has approved Carvykti® (ciltacabtagene autoleucel) for the treatment of adults with relapsed or refractory multiple myeloma (MM) after at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. Previously, the treatment was only approved for relapsed or refractory MM after 4 or more prior lines of therapy.
Carvykti is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Upon binding BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.
The approval was based on data from the randomized, open-label, phase 3 CARTITUDE-4 study (ClinicalTrials.gov Identifier: NCT04181827), which evaluated the efficacy and safety of Carvykti in 419 adults with relapsed and lenalidomide-refractory MM who previously received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.
Study participants were randomly assigned 1:1 to receive either a sequence of apheresis, bridging therapy, lymphodepletion and Carvykti or the physician’s choice of standard therapy (daratumumab, pomalidomide and dexamethasone or bortezomib, pomalidomide and dexamethasone). The primary endpoint was progression free survival (PFS).
After a median follow-up of 15.9 months, the median PFS was 12 months (95% CI, 9.8-14) for the standard therapy arm and not evaluable (95% CI, 22.8-not evaluable [NE]) for the Carvykti arm (hazard ratio [HR], 0.41 [95% CI, 0.30-0.56]; P <.0001). The estimated PFS rate at 12 months was 75.9% (95% CI, 69.4-81.1) in the Carvykti arm and 49.5% (95% CI, 42.3-56.3) in the standard therapy arm.
Results also showed an overall response rate of 84.6% (95% CI, 79.0-89.2) in the Carvykti arm and 67.8% (95% CI, 61.0-74.0) in the standard therapy arm (P <.0001). Among responders, 74.0% (95% CI, 67.5-79.9) of patients in the Carvykti arm achieved complete response or better vs 22.3% (95% CI, 16.8-28.5) in the standard therapy arm (P <.0001).
In patients who achieved partial response or better or in those who achieved complete response or better, the estimated median duration of response was not reached in the Carvykti arm and was 16.6 months (95% CI, 12.9-NE) in the standard therapy arm.
“Carvykti demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” said Binod Dhakal, MD, Associate Professor, Medical College of Wisconsin, Division of Hematology and Oncology and investigator on the CARTITUDE-4 study. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”
Carvykti is supplied as a single dose for infusion containing a suspension of CAR-positive viable T cells in 1 infusion bag.
“We understand the urgency for patients in need of Carvykti, and we have been making considerable progress in increasing supply and availability in anticipation of this milestone approval,” said Tyrone Brewer, President, US Hematology, Johnson & Johnson Innovative Medicine. “We more than doubled manufacturing of Carvykti in 2023, we are striving to double again in 2024, and we will continue to invest in our capacity so we can provide this critical therapy to as many patients as possible.”