Quadruplet Therapy Demonstrates Efficacy for Treatment of Transplant-Ineligible Newly Diagnosed Multiple Myeloma
A quadruplet regimen of isatuximab, bortezomib, lenalidomide, and dexamethasone demonstrated efficacy and safety for older patients with newly diagnosed multiple myeloma (MM) ineligible for transplant, according to study results from the REST phase 2 clinical trial published in The Lancet Haematology.
Previous research has found long-term corticosteroid exposure is associated with increased infection risk. Researchers conducted a multicenter, single-arm study to assess the efficacy and tolerability of isatuximab (10 mg/kg IV), bortezomib (1.3 mg/m² SC weekly, cycles 1–8), lenalidomide (25 mg PO days 1 to 21), and dexamethasone (20 mg PO days 1, 8, 15, 22) limited to the first 2 28-day cycles in patients with newly diagnosed MM ineligible for autologous hematopoietic stem-cell transplantation (HSCT).
Next-generation flow cytometry was used to assess the primary end point, measurable residual disease (MRD)-negative complete response. Overall, 39 patients underwent treatment for MM with quadruplet therapy. The median follow-up was 27.0 months (interquartile range [IQR], 23.0 to 33.7) and the median treatment duration was 22 months (IQR, 15.2 to 28.8). A median MRD-negative complete response was achieved by 19 patients (37%; 95% confidence interval [CI], 25.3–51.0).
Among 18 patients (35%), disease progression or death. The most frequent grade 3 or higher adverse events during treatment were neutropenia (55%), infections (41%), and thrombocytopenia (22%). Serious adverse events were reported in 53% of patients, and 2 treatment-related deaths occurred.
"Isatuximab, weekly bortezomib, and lenalidomide with limited dexamethasone was active and safe as initial therapy for older patients with multiple myeloma ineligible for autologous HSCT," the researchers concluded.
"A modified quadruplet regimen in which dexamethasone is omitted after 2 cycles can be used in this patient population,” they added.
Source:
Askeland FB, Einar Haukås, Slørdahl TS, et al. Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial. The Lancet Haematology. Published online February 2025. doi: 10.1016/s2352-3026(24)00347-8
