Cilta-cel Boosts Overall Survival in New Early Line Multiple Myeloma Data
The data, from the CARTITUDE-4 clinical trial, compared outcomes to patients treated with standard of care options.
Binod Dhakal, MD
Johnson & Johnson subsidiary Janssen’s and Legend Biotech's ciltacabtagene autoleucel (cilta-cel; marketed as Carvykti) an FDA-approved BCMA-directed autologous chimeric antigen receptor T-cell (CAR-T) therapy, has produced significantly improved overall survival (OS) outcomes in comparison to patients treated with standard-of-care (SOC) therapy for lenalomide-reftractory multiple myeloma (MM) in newly updated data from the phase 3 CARTITUDE-4 clinical trial (NCT04181827).1
The trial randomly assigned participants with relapsed or lenalidomide-refractory MM, who had previously been treated with 1 to 3 prior lines of therapy that included a protesome inhibitor (PI) and an immunomodulatory agent (IMiD), to receive either cilta-cel (n = 208) or SOC (n = 211), which consisted of either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd). The median OS for patients treated with cilta-cel and patients treated with SOC were not reached at a median follow-up of 34 months (95 percent Confidence Interval [CI], not estimable (NE) – NE), (95 percent CI, 37.75 months – NE) (hazard ratio [HR], 0.55; 95 percent CI, 0.39-0.79; P = .0009). Furthermore, patients treated with cilta-cel displayed an OS rate of 76% at 30 months of follow-up while patients treated with SOC showed a 64% OS rate at the same time point. Janssen noted that the risk of death for patients who were treated with cilta-cel was decreased by 45% in comparison to patients who were treated with SOC.
For patients treated with cilta-cel, the median progression-free survival (PFS) was NR (95 percent CI, 34.50 months – NE); in patients treated with SOC the median PFS was 11.79 months (95 percent CI, 9.66-14.00). The company also added that 77% of patients treated with cilta-cel achieved a complete response (CR) or better, with an 85% overall response rate. In addition, patients treated with SOC had a median duration of response (DOR) of 18.7 months (95 percent CI, 12.9-23.7); the median DOR for patients treated with cilta-cel was NR (95 percent CI, NE-NE). On the Multiple Myeloma Symptom and Impact Questionnaire (MySlm-Q), median time to symptom worsening was NR for patients who received cilta-cel (95 percent CI, NE-NE) and 34.33 months for patients who received SOC (HR, 0.38; 95 percent CI, 0.24-0.61; P < .0001).
“The 3-year follow-up data from the Phase 3 CARTITUDE-4 study show a statistically significant and clinically meaningful improvement in OS and quality-of-life measures with Carvykti versus standard therapies—meaningful results that have the potential to transform the multiple myeloma treatment landscape,” Binod Dhakal, MD, an associate professor at the Medical College of Wisconsin, Division of Hematology and Oncology, said in a statement.1 “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.”
With regard to the safety analysis, which utilized a set of 208 patients treated with cilta-cel and 208 patients treated with SOC, treatment-emergent adverse events (TEAEs) graded as 3 to 4 were observed in 97% of patients treated in both groups. Cytopenia was noted to be the most common of these TEAEs. In the cilta-cel set, 64% of patients experienced treatment-emergent infections. Of these infection cases, 28% were grade 3 or grade 4. In the SOC set, 76% of patients experienced treatment-emergent infections, with 30% of cases being grade 3 or grade 4. Fifty patients treated with cilta-cel died, with 21 of the deaths attributed to progressive disease. On the other hand, 82 patients treated with SOC died, with 51 of the deaths attributed to progressive disease. Janssen stated that 7 patients treated with cilta-cel and 1 patient treated with SOC acquired hematologic second primary malignancies.
“Carvykti is the first and only cell therapy approved for the treatment of patients with myeloma as early as second line, and now also the first and only cell therapy to improve overall survival and demonstrate improved patient quality-of-life outcomes versus standard therapies for patients with lenalidomide-refractory multiple myeloma,” Jordan Schecter, MD, the vice president, disease area leader, multiple myeloma at Johnson & Johnson Innovative Medicine, added to the statement.1 “At Johnson & Johnson, we remain committed to addressing unmet need through the development of innovative treatments for patients and healthcare providers, and we look forward to submitting these results to local health authorities worldwide.”
Cilta-cel is currently approved by the FDA for use in adults with relapsed and lenalidomide-refractory MM who have been treated with at least 1 prior line of therapy, including a PI and an IMiD.2 In the European Union, it is approved for adult patients with relapsed/refractory (r/r) MM who have been treated with at least 1 prior line of therapy, including a PI and an IMiD, showed disease progression on their last therapy, and have disease that is lenalidomide-refractory.3 Notably, in August 2024, cilta-cel was approved by China’s National Medical Products Administration (NMPA) for the treatment of adults with r/r MM who previously received treatment with 3 or more lines of therapy, including 1 or more proteasome inhibitor and 1 immunomodulatory agent.4 The NMPA’s decision was made with reference to results from the phase 2 CARTIFAN-1 clinical trial (NCT03758417), which took place at multiple sites in China.
“The approval of cilta-cel in China market marks a key milestone and will bring significant benefits to many patients,” Ying Huang, PhD, the CEO of Legend Biotech, said in a statement.4 “Moving forward, we will continue to pursue our goal of curing patients, expand our clinical research, and enhance the accessibility of this innovative product to benefit more patients.”
