Source: Myeloma – Hematology Advisor
A novel sequential treatment program comprising VRD (bortezomib, lenalidomide, dexamethasone) induction, autologous stem cell transplantation (ASCT), KRD (carfilzomib, lenalidomide, dexamethasone) consolidation, and lenalidomide maintenance is feasible with promising efficacy in patients with newly diagnosed multiple myeloma (NDMM), according to research published in Cancer Science.
Investigators in Japan conducted a phase 2 clinical trial evaluating the safety and efficacy of the combined treatment strategy of 4 induction cycles with VRD, followed by bortezomib and high-dose melphalan with ASCT, 4 consolidation cycles with KRD, and lenalidomide maintenance until disease progression in patients with NDMM aged 20-65 years between 2017 and 2019. The primary endpoint was complete response (CR) rate following consolidation therapy with KRD.
The study included 141 patients (median age, 58 years; range, 36-65 years; 53.2% male). Most patients (83.7%) had a performance status of 0-1. Of patients available for cytogenetic analysis (n=121), 57.0% had high-risk cytogenetics and 17.4% had ultra-high-risk cytogenetics (≥2 high-risk cytogenetic abnormalities).
In the intent-to-treat population, a CR or better was achieved by 19.9% after induction, 39.7% after transplant, 58.9% after consolidation, and 62.4% after 1-year of maintenance therapy. At a median follow-up duration of 38 months, the 3-year progression-free survival (PFS) and overall survival rates were 83.5% and 92.5%, respectively.
In patients with ultra-high-risk and high-risk cytogenetics, the 3-year PFS trended toward lower than that of patients without any high-risk cytogenetics (61.2% vs 77.8% vs 89.4%, respectively).
Overall, treatment was discontinued in 22.0% patients due to unacceptable adverse events (AEs). Severe adverse events (grade ≥3) occurred in approximately 30% of patients. No treatment-related mortality occurred.
“Our study showed an encouraging outcome, with responses consistently deepening throughout the program,” the authors wrote in their report. “Future studies should assess whether the innovative therapeutic strategy incorporating the anti-CD38 antibody increases protocol completion rates and thereby enhances survival outcomes, particularly in patients with high-risk or ultra-high-risk cytogenetics.”
Limitations of the study included the single-arm design and lack of control arm, inclusion of only Japanese patients, potential selection bias, and relatively small sample size.
Disclosure: This research was supported by ONO PHARMACEUTICAL CO. LTD. and Bristol Myers Squibb K.K. Please see the original reference for a full list of disclosures.