Among patients with newly diagnosed, ultra-high risk multiple myeloma (MM) or plasma cell leukemia (PCL), a daratumumab, low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) combination used before, and a consolidation regimen of Dara-VR(d) after autologous stem cell transplant (ASCT) appears to improve progression-free survival (PFS) compared with conventional treatment strategies, according to research published in the Journal of Clinical Oncology.

The worse overall survival (OS) rates observed among patients who relapse necessitates identifying and stratifying patients with ultra-high risk disease. This category includes the presence of at least 2 independent genetic risk markers, such as del(1p) or gain(1q) copy-number translocations.

For this digital comparison study using data from the phase 2 OPTIMUM trial ( Identifier: NCT03188172), researchers evaluated the safety and efficacy of the OPTIMUM regimen compared with conventional strategies among patients with newly diagnosed, ultra-high risk MM or PCL.

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Overall, 107 patients were enrolled to the OPTIMUM study and received at least Dara-CVRd induction; data from 120 patients were included in the digital comparator arm, known as MyeXI.

In the OPTIMUM and comparator groups, the median ages at baseline were 62 and 60 years, respectively, 57.5% and 59.8% of patients were male sex, and 64.2% and 53.3% of patients had double-hit genetic disease.

A Bayesian statistical model indicated that the OPTIMUM regimen had a 99.5% chance of being clinically superior to standard treatments given in the comparator arm. In the OPTIMUM and comparator arms, the 30-month PFS rates were 77% and 39.8%, respectively; the 30-month OS rates were 83.5% and 73.5%.

Further analysis suggested that extended Dara-VR(d) consolidation after ASCT was highly deliverable, though 27.5% of patients had grade 3 or 4 thrombocytopenia, and 43.8% of patients had grade 3 or 4 neutropenia.

“Although this is not a registration study,” the authors wrote in their report, “the high PFS and OS rates in OPTIMUM, which compare favorably with MyeXI, suggest Dara-CVRd induction and extended Dara-VR(d) post-ASCT consolidation is a novel effective treatment option for the clinical management of patients with [ultra-high risk] MM and PCL, providing compelling evidence to support further evaluation of this treatment strategy.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.


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