Ciltacabtagene autoleucel demonstrated efficacious responses and significant improvements in survival over standard of care in triple class–relapsed/refractory multiple myeloma.
Ciltacabtagene autoleucel (JNJ-68284528; cilta-cel) demonstrated efficacious responses and significant improvements in survival over standard of care in triple class–relapsed/refractory multiple myeloma, according to the results of the phase 1b/2 CARTITUDE-1 trial (NCT03548207), which were presented at the 2021 European Hematologic Asstandard of careiation (EHA) Annual Congress.
The comparative efficacy of to treat patients with triple-class exposed relapsed/refractory multiple myeloma in the was significantly improved over treatment with standard of care.
Specifically, overall response rate (ORR), complete response (CR) or better, progression-free survival (PFS), and overall survival (OS) were all superior with cilta-cel compared with the selected cohort of patients from 3 global trials utilizing the standard of care anti-CD38 monoclonal antibody, daratumumab (Darzalex).
“In the absence of a direct comparison between cilta-cel and treatments used in clinical practice, this analysis demonstrated that cilta-cel offers substantially more clinical benefit than current standard of care therapies for patients with triple-class exposed relapsed and refractory multiple myeloma,” Katja Weisel, MD, of the University Hospital Hamburg, explained in her presentation of the data.
In CARTITUDE-1, eligible patients previously received at least 3 lines of prior therapy, with ECOG performance scores of 0 or 1 and evidence of progressive disease within 12 months of the last line of therapy. The final population of patients from the CARTITUDE-1 trial for this analysis included 97 patients.
The comparative control standard of care cohort was comprised of patients from the phase 3 POLLUX (NCT02076009) and CASTOR (NCT02136134) trials and the phase 1b EQUULEUS trial (NCT01998971). A total of 267 patients were included in this cohort since they met the eligibility criteria of the CARTITUDE-1 trial, contributing 378 observations.
The POLLUX study investigated daratumumab plus lenalidomide (Revlimid) and dexamethasone versus lenalidomide and dexamethasone. CASTOR evaluated daratumumab plus bortezomib (Velcade) and dexamethasone versus bortezomib and dexamethasone. The EQUULEUS trial featured daratumumab plus standard multiple myeloma regimens.
Patients in the standard of care cohort were treated with physician’s choice of chemotherapy after discontinuing study treatment, with the most common therapies including pomalidomide (Pomalyst; 25.9% of patients), lenalidomide (18%), bortezomib (17.7%), and carfilzomib (Kyprolis; 17.5%).
Median follow-up for patients in the CARTITUDE-1 trial was 18 months and 16.9 months for patients in the standard of care population.
Prior to adjusting for a range of clinically important factors, cilta-cel treatment led to a significantly improved ORR at 97.9% compared with standard of care ORR at 37.8% (odds ratio [OR], 78.06; 95% CI, 24.20-478.16; P < .0001). The same was true for CR or better, finding an 80.4% rate with cilta-cell compared with 1.6% with standard of care (OR, 254.53; 95% CI, 105.87-724.78; P < .0001).
The responses remained true after adjustments to the standard of care group, resulting in an ORR of 33.6% (OR, 133.01; 95% CI, 35.71-887.29, P < .0001) and CR or better of 0.7% (OR, 754.27; 95% CI, 114.19-35,258.00; P < .0001).
When examining survival outcomes prior to adjustment, the research found improved PFS and OS for cilta-cel compared with standard of care treatment. More, compared with standard of care after adjustment, cilta-cel showed a significant reduction in the risk of disease progression or death of about 76%; reduction in the risk of death was about 79%.
Specifically, the median PFS for patients in the standard of care group was 5.59 months while the median PFS was just reached for cilta-cel at month 23. More, the OS for patients treated with standard of care was 10.9 months, while the median was not reached with cilta-cel.
“Standard of care for patients with triple-class exposed relapsed/refractory multiple myeloma is comprised of a vast and highly heterogeneous set of treatment regimens,” wrote the investigators in their poster presentation of the data. “These analyses provide evidence of superior outcomes with ciltacel versus standard of care in patients with triple-class exposed relapsed/refractory multiple myeloma.”
Weisel K, Martin T, Krishnan A, et al. Comparison of Ciltacabtagene Autoleucel (Cilta-cel) in CARTITUDE-1 Versus Standard of Care in Triple-Class Exposed Multiple Myeloma Patients in Clinical Trials of Daratumumab. Presented at: 2021 European Hematologic Asstandard of careiation Congress; Virtual. June 9-17, 2021. Abstract EP977.