This phase 2 trial designed by the Nordic Myeloma Study Group (study #23/15) explored the response to ixazomib, lenalidomide, and dexamethasone (IRd) induction followed by a single autologous stem-cell transplantation (ASCT), IRd consolidation, and risk-based maintenance with either ixazomib + lenalidomide or lenalidomide alone among patients with newly diagnosed multiple myeloma. Interim safety and response rates are presented.
There was a total of 120 patients enrolled across 22 sites. In the induction phase, patients received 4 IRd cycles (ixazomib 4 mg on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; dexamethasone 40 mg weekly) in 28-day cycles. All patients received 2 IRd cycles as consolidation, followed by maintenance therapy at 3 months post-ASCT. Upon completion of consolidation and maintenance therapy, patients were stratified to high-risk status if any aberrations were detected by fluorescence in situ hybridization at inclusion (del17p at least 60%, t[4;14], t[14;16], t[14;20], or +1q), and received ixazomib 4 mg on days 1, 8, and 15, and lenalidomide 10 mg on days 1 to 21. Patients who were not classified as high risk received lenalidomide 10 mg on days 1 to 21, with the dose increasing to 15 mg after 3 cycles. Maintenance therapy for this cohort was continued until disease progression (DP). The primary end point was minimal residual disease (MRD), as determined by an 8-color EuroFlow of <0.01%. Secondary end points included flow-MRD negativity by 10-5, overall response, safety, and progression-free survival. Serologic responses will be assessed before cycles, and flow-MRD sampling will be performed and repeated every 6 months if patients achieved a stringent complete response (sCR) or complete response (CR).
Of 120 patients enrolled in the study, 48% met high-risk criteria. Stem-cell mobilization was performed for 107 (89%) patients. To date, 86 (72%) patients have received ASCT. The overall response rate (ORR) after ASCT was 93%. After IRd induction, 2% of patients achieved sCR; 5%, CR; 28%, very good partial response (VGPR); 48%, partial response (PR); 7%, stable disease (SD); and 7% had DP. Response rates before consolidation were 5%, sCR; 14%, CR; 28%, VGPR; 31%, PR; and 2%, DP.
Prior to the consolidation phase, 10 (8%) patients withdrew as a result of DP and 4 (3%) withdrew because of drug toxicity. Grade 3 toxic events included cytopenia with liver toxicity, hypersensitivity with hepatorenal failure, and 1 case of unexplained encephalitis. One patient withdrew from the study because of cyclophosphamide toxicity. Seven additional patients were withdrawn per investigator’s decision, based on their high tumor burden. One additional patient decided to withdraw from the study. The most common grade 3/4 serious adverse events were neutropenia (22%), followed by infections (22%), and fever (11%). In addition, 12 other patients demonstrated grade 3 elevated abnormal liver transaminases, 4 had grade 3 peripheral neuropathy, and 61 (51%) patients reported skin reactions (11 of which were grade 3 events). A total of 98 (82%) patients continue in the study, which includes 80% of the high-risk patients.
The ORR was 93% after induction treatment. Only 9 patients achieved SD. Post-ASCT, ≥VGPR was achieved in 47% of patients. A total of 98 patients of the original 120 (82%) continue in the study, including 80% of the high-risk patients.
Abstract 144. ASH 2020. December 5, 2020. A prospective phase 2 study to assess minimal residual disease after ixazomib, lenalidomide and dexamethasone treatment for newly diagnosed transplant eligible multiple myeloma patients.