CARTITUDE-2: Half of Earlier-Line Myeloma Patients Stay Progression-Free Five Years After Single CARVYKTI Infusion
核心洞察
Five-year follow-up of CARTITUDE-2 Cohort A showed 10 of 20 relapsed/refractory multiple myeloma (搜索) patients remained alive and progression-free without maintenance therapy after one cilta-cel infusion.
Median progression-free survival reached 60.5 months, median overall survival was not reached, and the five-year overall survival rate was 69.2% at a median follow-up of 60.7 months.
Long-term remissions occurred in patients with high-risk cytogenetics, with five of the ten progression-free patients carrying at least one high-risk abnormality and four carrying two or more.
A single infusion of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) left half of patients with early-line relapsed or refractory multiple myeloma (搜索) alive and progression-free for at least five years without maintenance therapy, according to long-term follow-up from the initial subgroup of cohort A in the Phase 2 CARTITUDE-2 study.
The data, presented at the 2026 International Myeloma Society Annual Meeting in Glasgow (Abstract #PA-288), cover 20 patients at a median follow-up of 60.7 months. Ten of 20 patients (50%) remained alive and progression-free five years or more after infusion without further anti-myeloma treatment. Median progression-free survival was 60.5 months, median overall survival was not reached, and the five-year overall survival rate was 69.2%.
Johnson & Johnson and its collaboration partner Legend Biotech both released the findings, which build on the durable treatment-free remissions previously observed in CARTITUDE-1, a study conducted in later lines of therapy. The companies said the results reinforce that earlier treatment with CARVYKTI may increase the likelihood of long-term remission and disease control, and add to emerging evidence suggesting the therapy may have curative potential in some patients.
"Five years ago, treatment-free remissions of this duration were difficult to imagine for many patients with relapsed or refractory multiple myeloma (搜索)," said Niels van de Donk, M.D., Ph.D., Professor of Hematology at Amsterdam UMC. "These new CARVYKTI 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."
Cohort Design and Endpoints
CARTITUDE-2 cohort A enrolled patients with relapsed or refractory multiple myeloma (搜索) who had received one to three prior lines of therapy, had been exposed to a proteasome inhibitor, and were refractory to lenalidomide. The primary endpoint was minimal residual disease (MRD) negativity. Patients in the initial cohort were followed to assess long-term outcomes after a single CARVYKTI infusion without maintenance therapy.
At five years, MRD was assessed by bone marrow in three patients and was not required per protocol. All three were MRD-negative at the deepest level tested (10-6), indicating no detectable disease by highly sensitive testing.
Long-term remissions were observed even among patients with high-risk disease features. Of the 10 patients who remained alive and progression-free at five years, five had at least one high-risk cytogenetic abnormality, including four patients with two or more high-risk features.
Safety With Extended Follow-Up
The safety profile observed with longer follow-up was consistent with the known safety profile of CARVYKTI, with no new CAR T-cell-related neurotoxicity reported. Since the previous analysis of cohort A at a median follow-up of approximately 30 months, one patient developed a new hematologic malignancy (acute myeloid leukemia (搜索)) and two deaths occurred, due to progressive disease and a new cancer.
CARVYKTI carries a boxed warning for cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, prolonged and recurrent cytopenia, and secondary hematological malignancies. Among 285 patients who received the therapy for relapsed or refractory multiple myeloma (搜索) in the CARTITUDE-1 and CARTITUDE-4 studies, CRS occurred in 84% (238/285), including Grade 3 or higher in 4% (11/285), and one or more neurologic toxicities occurred in 24% (69/285), including Grade 3 or higher in 7% (19/285). Myeloid neoplasms occurred in 5% (13/285) of those patients, with a median time to onset of 447 days.
In CARTITUDE-4, a randomized controlled trial, a numerically higher percentage of early deaths occurred in the CARVYKTI arm compared with the control arm: 29 of 208 patients (14%) versus 25 of 211 (12%) among deaths within the first 10 months from randomization. Of the 29 deaths in the CARVYKTI arm, 10 occurred before infusion, all from disease progression, and 19 after infusion, of which 16 were due to adverse events, most commonly infection.
Regulatory Position and Mechanism
CARVYKTI received U.S. Food and Drug Administration approval in February 2022 for adults with relapsed or refractory multiple myeloma (搜索) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In April 2024, following an 11 to 0 FDA Oncologic Drugs Advisory Committee recommendation, the agency approved the therapy for patients who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent and who are refractory to lenalidomide. The European Medicines Agency approved a Type II variation for the same earlier-line indication in April 2024, and Japan's Ministry of Health, Labour and Welfare granted a label expansion in July 2026 allowing use after at least one prior therapy.
The therapy is a BCMA (搜索)-directed, autologous T-cell immunotherapy that reprograms a patient's own T cells with a transgene encoding a chimeric antigen receptor directed at BCMA, which is primarily expressed on the surface of malignant multiple myeloma (搜索) B-lineage cells as well as late-stage B cells and plasma cells. The CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. CARVYKTI is available in 17 markets worldwide and has been used to treat more than 13,000 patients globally.
Janssen Biotech (搜索), a Johnson & Johnson company, entered an exclusive worldwide license and collaboration agreement with Legend Biotech USA in December 2017 to develop and commercialize the therapy.
Disease Burden
Multiple myeloma (搜索) is the third most common blood cancer worldwide, with more than 180,000 new cases diagnosed globally each year. People living with the disease have a five-year survival rate of 59.8%. In the United States, more than 36,000 people are estimated to be diagnosed in 2026 and more than 10,000 are expected to die from the disease. Most patients are diagnosed after symptoms such as bone problems, low blood counts, elevated calcium, kidney problems, or infections.
"These results add to the growing body of evidence suggesting that CARVYKTI may have curative potential for some patients, and reinforce the value of bringing highly effective therapies to patients earlier in their treatment journey," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson.
CARTITUDE-2 (NCT04133636) remains ongoing as a multicohort Phase 2 study evaluating the efficacy and safety of cilta-cel across different clinical settings, including patients with one to three prior lines of therapy, and continues to generate long-term follow-up data on depth and durability of response.