CARVYKTI gives five-year remissions to 50% in early-line myeloma
Johnson & Johnson has reported that half of a 20-patient cohort in the Phase 2 CARTITUDE-2 study remained alive and progression-free five years after a single infusion of CARVYKTI (ciltacabtagene autoleucel; cilta-cel), with no maintenance therapy required. The data, presented at the International Myeloma Society Annual Meeting in Glasgow, mark the longest published follow-up for the BCMA-directed CAR-T cell therapy in early-line relapsed or refractory multiple myeloma (RRMM).
The cohort A patients had received one to three prior lines of therapy, were exposed to a proteasome inhibitor, and were refractory to lenalidomide. At a median follow-up of 60.7 months, the five-year overall survival rate was 69.2% and median progression-free survival reached 60.5 months. Of the ten patients who remained progression-free at five years, five had at least one high-risk cytogenetic abnormality, and four had two or more high-risk features, suggesting the durability of response extended into a typically harder-to-treat population.
Depth of response
Three patients who reached the five-year mark had bone marrow MRD assessments, all returning negative results at the 10⁻⁶ sensitivity threshold, indicating no detectable disease by highly sensitive testing. The primary endpoint of the CARTITUDE-2 study was MRD negativity, and these long-term data provide context on how that early molecular response can translate into sustained clinical benefit.
The safety profile with extended follow-up was described as consistent with the established cilta-cel label. No new CAR-T-related neurotoxicity was reported. Since the prior analysis, one patient developed acute myeloid leukaemia, a secondary haematologic malignancy that has been observed in the broader CAR-T class, and two further deaths occurred due to progressive disease and a new cancer.
Niels van de Donk, Professor of Hematology at the University Medical Center Amsterdam, who has advisory relationships with Johnson & Johnson, said the findings provide "additional evidence that when highly effective, established therapies are used earlier in the disease course, more patients may have the opportunity to achieve deep, durable remissions and long-term disease control without maintenance."
Competitive and regulatory context
Cilta-cel received US approval in April 2024 for second-line RRMM, and the European Commission extended its indication in the same month to cover patients who had received at least one prior therapy, including a proteasome inhibitor and an immunomodulatory drug, and who were refractory to lenalidomide. These CARTITUDE-2 data, while from a small exploratory cohort, are designed to build the clinical narrative supporting that earlier-line positioning.
The RRMM landscape is crowded with bispecific antibodies targeting BCMA and GPRC5D, several of which also originate from Johnson & Johnson's own portfolio. The company's broader strategy appears to be establishing CAR-T as a potentially curative option in earlier lines before bispecifics and newer combinations erode the later-line differentiation that cilta-cel built in CARTITUDE-1. Competing BCMA-directed CAR-T programmes from other sponsors remain active, and the long-term data question of whether any single-infusion cell therapy can achieve functional cure in a meaningful patient proportion will be central to reimbursement negotiations across European health technology assessment bodies in the coming years. The CARTITUDE-4 Phase 3 trial, which is evaluating cilta-cel versus standard of care in lenalidomide-refractory patients, is expected to provide the pivotal-level dataset that regulators and payers will require to broaden access further.