The phase 3 CASSIOPEIA study met its primary end point of progression-free survival with daratumumab maintenance in newly-diagnosed multiple myeloma eligible for autologous stem cell transplant.
Topline findings from the second part of the phase 3 CASSIOPEIA clinical trial showed that the primary end point of progression-free survival (PFS) was met with daratumumab as maintenance treatment of patients with newly-diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT), according to a press release.1
These data demonstrated a PFS hazard ratio (HR) of 0.53 (95% CI, 0.42-0.68), with a 47% reduction in the risk of disease progression or death with daratumumab. The safety profile also appeared consistent with the known daratumumab profile, and no new safety signals were observed.
Based on the findings from this pre-planned interim analysis, an Independent Data Monitoring Committee had recommended unblinding the study results.
“Following the positive data from the first part of the CASSIOPEIA study, we are very pleased to see this benefit. We are appreciative of the efforts of the French Intergroupe Francophone du Myeloma (IFM), of the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen for their work on this study.
This randomized, open-label, multicenter study (NCT02541383) was conducted by the IFM in collaboration with HOVON and Janssen. Overall, 1085 patients with newly-diagnosed multiple myeloma who were symptomatic and eligible for high-dose chemotherapy and ASCT. The first part of the study randomized patients to receive either induction and consolidation daratumumab with bortezomib, thalidomide, and dexamethasone (D-VTd) or VTd alone. The primary end point was the number of patients that achieved a stringent complete response.
Patients who achieved a response were included in the second part of the study, in which they underwent a second randomization to receive either maintenance daratumumab at 16 mg/kg every 8 weeks for up to 2 years or no further treatment, in which patients underwent observation. The primary end point of this study is PFS.
Janssen has begun discussing a potential regulatory submission of this therapy to health authorities.
Previous findings from the CASSIOPEIA study were presented at the 17th International Myeloma Workshop and published in the Lancet, which demonstrated benefit with D-VTd compared with VTd alone. The daratumumab regimen induced a 34% reduction in the risk of disease progression or death among patients with International Staging System (ISS) stage III disease (HR, 0.66; 95% CI, 0.32-1.39) and a 33% reduction among patients with high-risk cytogenetics of del(17p) or t(4;14) with D-VTd versus VTd (HR, 0.67; 95% CI, 0.35-1.30).2
A benefit with stringent complete response rate was not observed with the experimental regimen among patients with ISS stage III disease (P =.8506) or high-risk cytogenetics (P =.4839).
Based on the findings from part 1 of the study, the FDA granted an approval to a supplemental Biologics License application for D-VTd for the treatment of patients with newly-diagnosed multiple myeloma who are eligible for ASCT.1
Daratumumab currently serves as a backbone therapy in treatment of patients with multiple myeloma. It has also previously received approval for the treatment of adult patients in combination with carfilzomib (name) and dexamethasone for relapsed/refractory multiple myeloma following 1 to 3 prior lines of therapy, in combination with lenalidomide and dexamethasone for newly-diagnosed myeloma ineligible for ASCT, in combination with bortezomib and melphalan plus prednisone for newly-diagnosed myeloma ineligible for ASCT, and in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for multiple myeloma following at least 1 prior therapy. The agent is also approved in combination with pomalidomide and dexamethasone for myeloma following 2 prior lines of therapy, including lenalidomide and a proteasome inhibitor, while daratumumab monotherapy also received approval previously for the treatment of patients with myeloma following at least 3 prior liens, including a PI and an immunomodulatory agent or who are double-refractory to a PI and immunomodulatory agent.
Daratumumab is the first monoclonal antibody to receive FDA approval for the treatment of multiple myeloma. The agent is also available under multiple indications in Europe, in which it was the first subcutaneous CD38 antibody approved for myeloma, and in Japan.
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1. Genmab Announces IFM, HOVON and Janssen Achieve Positive Topline Results in Second Part of Phase 3 CASSIOPEIA Study of Daratumumab in Multiple Myeloma at Pre-planned Interim Analysis. News Release. October 21, 2020. Accessed October 22, 2020. https://bit.ly/2HsjywP
2. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29-38. doi: 10.1016/S0140-6736(19)31240-1.