Johnson & Johnson has disclosed new findings from the phase 3 CARTITUDE-4 trial, highlighting a single dose of Carvykti (ciltacabtagene autoleucel, cilta-cel) markedly boosts rates of minimal residual disease (MRD) negativity (10-5) among patients with relapsed or refractory multiple myeloma (RRMM). These patients are lenalidomide-refractory, having undergone one to three prior therapy lines, including a proteasome inhibitor, and Carvykti’s performance surpasses that of the standard regimens featuring pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd). MRD is a critical indicator of extended survival prospects for multiple myeloma patients. These promising results build on the overall survival (OS) benefits recently shared at the International Myeloma Society gathering earlier this year, positioning Carvykti as the inaugural cell therapy to noticeably enhance OS when measured against conventional treatments for multiple myeloma sufferers. The findings were showcased via an oral presentation at the 2024 American Society of Hematology (ASH) Annual Meeting (Abstract #1032).
“Carvykti has definitively proven its significant role in elevating overall survival and enhancing progression-free survival over traditional therapies,” expressed Dr. Rakesh Popat from University College London Hospitals NHS Foundation Trust, UK, and leading investigator for the study. “The MRD negativity outcomes point to deeper responses over standard treatments for multiple myeloma patients, further highlighting the early advantages of Carvykti as a single infusion.”
The phase 3 CARTITUDE-4 study compared Carvykti to standard therapies of PVd or DPd for treating RRMM patients as early as post one prior treatment line. Those treated, having received up to three prior therapy lines including a proteasome inhibitor and immunomodulatory agent (IMiD) and being lenalidomide-refractory, were randomized (Carvykti, n=208; standard therapies, n=211). Over a median follow-up of nearly three years (34 months), MRD-negativity rates doubled in patients receiving Carvykti compared to standard options (89% opposed to 38%; P<0.0001). After 2.5 years, sustained (12+ months) MRD-negative complete response or better in those treated with Carvykti was quintuple that of the standard treatments (52% contrasting with 10%; P<0.0001). A post-hoc comparison between CARTITUDE-4 and CARTITUDE-1 highlighted the higher rates of MRD negativity, progression-free survival (PFS), and OS when Carvykti is applied earlier in treatment.
“We are thrilled to showcase the latest MRD negativity outcomes from the CARTITUDE-4 study demonstrating that Carvykti, approved as the only cell therapy for myeloma treatment as early as the second line, offers profound long-term remission rates, encompassing progression-free survival and overall survival advantages,” remarked Dr. Jordan Schecter, Johnson & Johnson Innovative Medicine’s vice president of multiple myeloma disease area. “It’s becoming increasingly evident that achieving MRD negativity is a pivotal objective with CAR-T treatment in myeloma, as these analysis results demonstrate higher MRD rates with earlier intervention.”
Additional data regarding patient-reported outcomes (PROs) and time to symptom deterioration (TTW) with Carvykti will be presented in an ASH 2024 poster presentation (Abstract #2002). Reports suggest patients treated with Carvykti experienced significantly longer symptom TTW compared to standard treatments. After three years, 83% of patients under Carvykti treatment hadn’t faced worsening functional impacts compared to 69% of those on standard therapies.
CARTITUDE-4 (NCT04181827) stands as the first randomized phase 3 study assessing Carvykti’s efficacy and safety. The study juxtaposes Carvykti with conventional PVd or DPd treatments in adult patients with relapsed and lenalidomide-refractory multiple myeloma after one to three treatment lines. The primary endpoint centers on PFS, with safety, OS, MRD negativity rate, and overall response rate as secondary endpoints.
Carvykti is a BCMA-directed, autologous T-cell immunotherapy genetically engineered through reprogramming a patient’s T-cells with a CAR-encoding transgene targeting BCMA-positive cells. BCMA, found dominantly on malignant multiple myeloma B-lineage cells and late-stage B/plasma cells, becomes the target as the CAR prompts T-cell activation, expansion, and destruction of these target cells.
Carvykti (cilta-cel) received FDA approval in February 2022 for treating adults with relapsed or refractory multiple myeloma following four or more therapy lines, including a proteasome inhibitor, an IMiD, and an anti-CD38 monoclonal antibody. In April 2024, Carvykti was sanctioned as the first cell therapy in the US for adults with relapsed or refractory multiple myeloma post at least one therapy line involving a proteasome inhibitor, an IMiD, and who are lenalidomide-refractory. The European Medicines Agency also approved a Type II variation for Carvykti in April 2024.
In December 2017, Janssen Biotech, Inc., a Johnson & Johnson entity, entered an exclusive worldwide licensing and collaboration arrangement with Legend Biotech USA, Inc. to develop and market Carvykti.
Multiple myeloma, an incurable blood cancer affecting plasma cells in the bone marrow, is the third-most common blood cancer globally. In 2024, over 35,000 individuals in the US were projected to be diagnosed with multiple myeloma, with more than 12,000 deaths anticipated. The 5-year survival rate for people living with multiple myeloma is 59.8%. While some diagnosed individuals might show no initial symptoms, others may experience bone pain or fractures, anemia, fatigue, elevated calcium levels, as well as kidney or infection concerns.