Study Suggests Dara-CVRd Is Superior to Conventional Myeloma Treatment Regimens

Daratumumab, low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) as induction therapy for autologous hematopoietic stem cell transplantation (AHSCT) and post-transplant consolidation therapy improved progression-free survival (PFS) in ultra-high-risk patients with newly diagnosed multiple myeloma (MM) or plasma cell leukemia (PCL), according to the multicenter OPTIMUM study, which was published in the Journal of Clinical Oncology.

“To our best knowledge, this is the first trial specific for [ultra-high-risk newly diagnosed] MM and PCL showing a majority of sustained responses in this difficult-to-treat population with a follow-up beyond three years,” suggested the study authors, who were led by Martin Kaiser, MD, of the Institute of Cancer Research in London.

In OPTIMUM, patients were classified as ultra-high-risk based on presence of two or more genetic risk markers, including t(4;14)/t(14;16)/t(14;20), del(1p), gain(1q), del(17p), and SKY92. The authors compared OPTIMUM patient outcomes with those recorded in the contemporaneous Myeloma XI trial that treated similar patients with carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide, or lenalidomide, dexamethasone, and cyclophosphamide followed by AHSCT and lenalidomide  maintenance or observation.

Overall, 103 patients met the eligibility criteria and received Dara-CVRd. According to the OPTIMUM authors, 18-month PFS Bayesian framework estimates gave the OPTIMUM regimen a 99.5% chance of being superior to the Myeloma XI regimens. Additionally, PFS and OS at 30 months were 77.0% and 83.5% for OPTIMUM patients compared with 39.8% and 63.5% for Myeloma XI patients, respectively.

“Our results suggest that Dara-CVRd induction and extended post-AHSCT Dara-CVRd consolidation markedly improve PFS for [ultra-high-risk newly diagnosed] MM patients over conventional management, supporting further evaluation of this strategy,” Dr. Kaiser and colleagues concluded.

Reference

Kaiser MF, Hall A, Walker K, et al. Daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone as induction and extended consolidation improves outcome in ultra-high-risk multiple myeloma. J Clin Oncol. 2023;41(23):3945-3955. doi:10.1200/JCO.22.02567