Posted: Wednesday, February 1, 2023
According to Martin F. Kaiser, MD, FRCP, FRCPath, of the Royal Marsden Hospital, London, and colleagues, the prevention of relapse remains a fundamental challenge in the treatment of patients with ultra–high-risk multiple myeloma. An analysis of the UK OPTIMUM/MUKnine trial, which was presented during the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 758), supported extended, risk-stratified therapy after autologous stem cell transplantation (ASCT) in this setting.
In the OPTIMUM trial, a total of 107 patients with ultra–high-risk, newly diagnosed disease received induction therapy with daratumumab plus CVRd (cyclophosphamide, bortezomib, lenalidomide, and dexamethasone), bortezomib-augmented ASCT, and consolidation therapy with daratumumab plus VRd (first; n = 80 completed) and daratumumab plus VR (second; n = 74 completed). The results were contextualized with the clinical outcomes of the Myeloma XI trial, in which patients were administered induction therapy with CRd or carfilzomib plus CRd followed by ASCT.
The median duration of progression-free survival was not reached in the OPTIMUM patients. The estimated 30-month progression-free survival rate at the end of consolidation therapy was 77.0%. In the Myeloma XI trial, the 30-month progression-free survival rate was 49.7% in patients treated with carfilzomib plus CRd, 34.1% in those who received CRd, and 39.8% in the overall population. Over time, the investigators observed a separation between the OPTIMUM and Myeloma XI progression-free survival curves; this suggests there may be a sustained beneficial effect of ongoing consolidation therapy.
During the second consolidation treatment, the most frequently reported adverse events of grades 3 and 4 were neutropenia (43.8%), thrombocytopenia (27.5%), and infection (15.0%). A total of 13.8% of patients experienced peripheral neuropathy of grade 2 or higher after the second consolidation treatment; no cumulative increase from the first consolidation treatment was reported. Of the 47 OPTIMUM patients who were evaluable for measurable residual disease (MRD) after the second consolidation treatment, 44 had undetectable MRD at a threshold of 10-5 cells.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
2022 ASH Annual Meeting and Exposition