Johnson & Johnson announced long-term results from the Phase 3 CARTITUDE-4 study, revealing that a single infusion of Carvykti (ciltacabtagene autoleucel) significantly extended overall survival (OS) in patients with relapsed or lenalidomide-refractory multiple myeloma. These patients had received at least one prior line of therapy, including a proteasome inhibitor (PI). The study demonstrated a 45 percent reduction in the risk of death compared to standard therapies, marking Carvykti as the first and only cell therapy to improve OS versus standard therapies in this patient population as early as the second line. The findings were presented at the 2024 International Myeloma Society (IMS) Annual Meeting.
CARTITUDE-4 Study Details
The Phase 3 CARTITUDE-4 study evaluated Carvykti against standard therapies, specifically pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd), for treating relapsed or lenalidomide-refractory multiple myeloma after one prior line of therapy. Patients who had received one to three prior lines of therapy, including a PI and immunomodulatory agent (IMiD), and were lenalidomide-refractory, were randomized (Carvykti, n=208; standard therapies, n=211).
After a median follow-up of almost three years (34 months), the median OS for patients treated with Carvykti or standard therapies was not reached (NR) (95 percent Confidence Interval [CI], not estimable (NE) – NE) and (95 percent CI, 37.75 months – NE) (Hazard Ratio [HR], 0.55; 95 percent CI, 0.39-0.79; P= 0.0009). At the 30-month follow-up, the OS rates were 76 percent for patients in the Carvykti arm and 64 percent for those in the standard therapies arm. These data underscore that Carvykti significantly extended OS for patients compared to standard therapies.
Clinical Significance
In patients randomized to the Carvykti arm, the risk of death was reduced by 45 percent compared to standard therapies, demonstrating clinically meaningful responses early after the first relapse. The median progression-free survival (PFS) was NR in patients treated with Carvykti (95 percent CI, 34.50 months – NE) and 11.79 months (95 percent CI, 9.66-14.00) in patients treated with standard therapies, indicating sustained deep and durable responses. Patients treated with Carvykti had a 77 percent complete response or better, and an 85 percent overall response rate. Furthermore, Carvykti demonstrated a 62 percent minimal residual disease (MRD) negativity (10^-5) and 57 percent MRD-negativity (10^-6) compared to standard therapies (18.5 percent, 9 percent), respectively. The median duration of response was NR (95 percent CI, NE-NE) in patients treated with Carvykti and 18.7 months (95 percent CI, 12.9-23.7) for patients treated with standard therapies. The median time to symptom worsening, based on the Multiple Myeloma Symptom and Impact Questionnaire (MySlm-Q), was NR (95 percent CI, NE-NE) with Carvykti and 34.33 months (95 percent CI, 32,20-NE) with standard therapies (HR, 0.38; 95 percent CI, 0.24-0.61; P< 0.0001).
Safety Profile
The safety profile of Carvykti versus standard therapies was consistent with previous analyses. In the safety analysis (Carvykti, n=208; standard therapies, n=208), 97 percent of patients in both arms experienced grade 3/4 treatment-emergent adverse events (TEAEs), with cytopenia being the most common. Treatment-emergent infections occurred in 64 percent of patients in the Carvykti arm and 76 percent of patients who received standard therapies, with 28 percent and 30 percent being classified as grade 3/4, respectively. In the Carvykti arm, there were seven patients with hematologic second primary malignancies, 50 patients died, and of those patients, 21 died due to progressive disease. One patient treated with standard therapies experienced a hematologic second primary malignancy, 82 patients died, and of those patients, 51 died due to progressive disease.
Expert Commentary
"The three-year follow-up data from the Phase 3 CARTITUDE-4 study show a statistically significant and clinically meaningful improvement in overall survival and quality-of-life measures with Carvykti versus standard therapies—meaningful results that have the potential to transform the multiple myeloma treatment landscape," said Dr. Binod Dhakal, Associate Professor of Medicine at the Medical College of Wisconsin, Division of Hematology, and study investigator. "This adds to the growing body of data reinforcing the promise of a single infusion of Carvykti, which, in addition to demonstrating a significant overall survival benefit, also offers patients the opportunity of a period free from multiple myeloma treatment as early as second line."
Regulatory Status
Carvykti is approved in the U.S. and Europe for treating adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a PI, IMiD, and are refractory to lenalidomide. Globally, Carvykti has been launched in 5 countries, treating more than 3,500 patients.
