Johnson & Johnson's Carvykti (ciltacabtagene autoleucel), a BCMA-directed CAR-T cell therapy, has demonstrated promising results in the CARTITUDE-4 study, potentially shifting its use to earlier lines of treatment for multiple myeloma. The study's findings suggest a significant improvement in progression-free survival (PFS) compared to standard treatment regimens, paving the way for Carvykti to become a more prominent therapy for patients with relapsed or refractory disease.
CARTITUDE-4 Study Details
The CARTITUDE-4 trial evaluated Carvykti in patients who had received one to three prior lines of therapy. These patients had relapsed after at least one regimen containing lenalidomide, a common first-line treatment for multiple myeloma. The study compared Carvykti to two three-drug regimens: pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd).
Significant Improvement in Progression-Free Survival
An independent data monitoring committee recommended unblinding the study due to the significant improvement in PFS observed in the Carvykti arm. While the final results, including overall survival data (a secondary endpoint), will be presented at an upcoming medical congress, the initial findings are highly encouraging.
Implications for Treatment Landscape
Currently approved as a fifth-line or later therapy, Carvykti's potential expansion into earlier lines of treatment could position it ahead of Bristol-Myers Squibb and 2Seventy bio's Abecma (idecabtagene vicleucel), which is also indicated for later-line use. J&J's chief executive, Joaquin Duato, has identified multiple myeloma as a key driver for the company's pharmaceutical division, emphasizing the importance of expanding Carvykti's use alongside other therapies like Darzalex (daratumumab) and bispecific antibodies such as Tecvayli (teclistamab) and talquetamab.
Commercial Potential
Analysts predict potential blockbuster sales for Carvykti if it secures approval for second-line treatment. The estimated patient population for second-line use is around 36,000 per year, significantly larger than the approximately 3,000 patients eligible for fifth-line treatment. Both J&J and BMS are also exploring the use of their respective CAR-T therapies as first-line treatments in ongoing trials (CARTITUDE-5/CARTITUDE-6 and KarMMa-9, respectively).
BCMA-Targeted Therapies in Myeloma
Carvykti and Abecma target B-cell maturation antigen (BCMA), a key protein expressed on multiple myeloma cells. Other BCMA-targeted therapies include GlaxoSmithKline's Blenrep (belantamab mafodotin), an antibody-drug conjugate, and several bispecific antibodies in development from companies like Regeneron and Amgen. These therapies offer different mechanisms of action and treatment approaches for patients with multiple myeloma.
