After putting on a strong performance in preventing disease progression in the earlier treatment of multiple myeloma, Johnson & Johnson and Legend Biotech’s Carvykti has once again mounted a major benefit—this time in prolonging patients’ lives.
A single dose of the star BCMA CAR-T therapy significantly slashed the risk of death by 45% compared with two traditional combination treatments in myeloma patients who had received at least one prior line of therapy, according to an update of the phase 3 CARTITUDE-4 trial. Combinations of either Bristol Myers Squibb’s Pomalyst, Takeda’s Velcade and dexamethasone (PVd), or J&J’s Darzalex, Pomalyst and dexamethasone (DPd) served as the trial's comparators.
Although neither arm reached its median overall survival time, 76.4% of patients in the Carvykti cohort were estimated to be alive at month 30, versus 63.8% for the control arm.
The data were presented at the 2024 International Myeloma Society (IMS) annual meeting after investigators followed patients in CARTITUDE-4 for a median duration of 33.6 months. An earlier data cut from the study, linking Carvykti to a 59% lower risk of disease progression or death, enabled the med's second-line approval from the FDA in April.
As the FDA has pointed out and warned in Carvykti’s label, treatment with the med may come with a higher risk of death early on. But there’s no question about Carvykti’s ability to extend patients’ life expectancy over the long term.
The overall survival curves flipped in Carvykti’s favor at around month 12, and its advantage continued to widen after that, the data showed. In fact, the Carvykti curve roughly plateaued at about month 31, indicating that very few deaths happened afterward. The standard-of-care curve continued to experience notable declines every few months.
Investigators also offered another look at patients’ quality of life from CARTITUDE-4. Despite starting with relative worse baseline performance on several health metrics such as physical and social functioning, plus pain and fatigue symptoms, patients in the Carvykti arm experienced improved overall health status over time. Their counterparts in the standard-of-care arm didn't experience the same improvements.
Patient-reported outcomes from CARTITUDE-4 “remain as stunning as ever to support CAR-T in earlier lines” of myeloma treatment, Rahul Banerjee, M.D., from Fred Hutchinson Cancer Center tweeted Friday. He pointed to how patients’ pain scores were consistently better in the Carvykti arm and “how quickly and durably patient fatigue improves with CAR-T” compared with the standard-of-care triplet group.
An overall survival win further differentiates Carvykti from Bristol Myers Squibb and 2seventy bio’s rival CAR-T therapy Abecma, which wasn’t able to demonstrate that it could extend patients’ lives in the KarMMa-3 trial, which enrolled patients one treatment line later than those in CARTITUDE-4.
But Abecma may still have a place in the myeloma market. Also at the IMS meeting, Doris Hansen, M.D. from Moffitt Cancer Center presented a multicenter retrospective study on behalf of the U.S. Multiple Myeloma Immunotherapy Consortium comparing Carvykti with Abecma in previously treated myeloma.
The study examined results from 641 real-world patients, including 586 patients who actually received either one of the BCMA CAR-T products as intended. The patients were matched between the two arms based on multiple factors for comparison. Some patients didn’t get the CAR-T drugs mainly because of disease progression, death or manufacturing failures.
The updated analysis linked Carvykti to better efficacy, including a 56% reduction in the risk of progression or death, versus Abecma in the entire intent-to-treat population, or 53% in those who were infused. Overall survival was similarly in favor of the J&J/Legend med.
However, Carvytki also showed notably higher rates of some toxicities, including severe cytokine release syndrome (5.5 times as likely as Abecma) and delayed neurotoxicity (21 times as likely).
“[T]his confirms what many of us have seen anecdotally,” Banerjee said Friday in another X post, pointing to the increased efficacy but certain adverse events with Carvykti.
This analysis will help doctors select between the two products based on the patient characteristics.
Carvykti, viewed as the more efficacious BCMA CAR-T therapy, has been pulling ahead of Abecma in market share. In another blow to Abecma, BMS and 2seventy last week decided to discontinue the phase 3 KarMMa-9 trial, which had been evaluating Abecma as a first-line maintenance treatment in patients with newly diagnosed multiple myeloma who had experienced a suboptimal response to a stem cell transplant.
Carvykti's first-line studies are moving forward: CARTITUDE-5 has finished enrollment while CARTITUDE-6 is expected to be fully enrolled next year.