Based on a phase 2 trial, interim results exploring the response to ixazomib, lenalidomide, and dexamethasone (IRd) induction followed by a single autologous stem-cell transplantation (ASCT), IRd consolidation, and risk-based maintenance found a 93% overall response rate (ORR).
Designed by the Nordic Myeloma Study Group (NMSG; study #23/15), a phase 2 trial explored the response to IRd induction followed by a single ASCT, IRd consolidation, and risk-based maintenance either with IR or lenalidomide among patients with newly diagnosed MM. Interim safety and response rates are presented after IRd × 4 induction for all patients and for 87% of patients before consolidation.
A total of 120 patients were enrolled across 22 sites. As induction, patients received 4 IRd cycles (ixazomib 4 mg on days 1, 8, 15; lenalidomide 25 mg on days 1-21; dexamethasone 40 mg weekly) in 28-day cycles. Mobilization and ASCT were performed based on standard practice. All patients will receive 2 IRd cycles as consolidation followed by maintenance therapy 3 months after ASCT. Thereafter, patients will be stratified to high risk if any aberrations are detected by fluorescence in situ hybridization at inclusion (del17p ≥60%, t[4;14], t[14;16], t[14;20] or +1q) and will receive ixazomib 4 mg on days 1, 8, and 15 and lenalidomide 10 mg on days 1 through 21. Patients not classified as high risk will receive lenalidomide 10 mg on days 1 through 21 with the dose increasing to 15 mg after 3 cycles. Maintenance therapy will continue until disease progression (DP). The primary end point is minimal residual disease (MRD), which is determined by an 8-color EuroFlow of <0.01%. Secondary end points include flow-MRD negativity by 10-5, overall response, safety, and progression-free survival (PFS). Serologic responses will be assessed before cycles, and flow-MRD sampling will be performed and repeated every 6 months if either stringent complete response (sCR) or complete response (CR) is achieved.
A total of 120 patients were enrolled in the study, 46% of whom met criteria for being high risk. As of July 2020, stem-cell mobilization was performed for 101 (84%) patients. Currently, 86 (72%) patients have received ASCT. ORR was 93%. Response rates after IRd × 4 induction were sCR (2%), CR (6%), very good partial response (VGPR; 24%), partial response (PR; 53%), stable disease (SD; 7%), and DP (4%). Response rates before consolidation were sCR (3%), CR (14%), ≥VGPR (19%), PR (30%), SD (2%), and DP (4%).
Before consolidation, 10 (8%) patients withdrew because of DP and 4 (3%) withdrew because of toxicity. Toxicity events included a grade 3 cytopenia with liver toxicity, hypersensitivity with hepatorenal failure, and a case of unexplained encephalitis. One patient withdrew because of cyclophosphamide toxicity during stem-cell mobilization. Seven additional patients withdrew per the decision of the physician because of high tumor burden based on M-protein level and achieving only SD during induction. One additional patient decided to withdraw. Currently, there are 58 grade 3/4 serious adverse events that have been reported for 39 (33%) patients; 57% were infections. In addition, 3 patients had grade 3 liver-related events, 2 had grade 3 peripheral neuropathy, and 17 (14%) reported skin reactions (4 grade 3 events). A total of 98 (82%) patients continue in the study, including 80% of those who were high risk.
In this study, ORR was 93% after induction treatment. A total of 9 patients only achieved SD, of whom 7 were withdrawn before stem-cell mobilization due to high tumor burden. In 37% of patients, ≥VGPR was achieved post-ASCT. Of the original 120 patients, a total of 98 (82%) patients continued in the study, including 80% of the patients with high risk.
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.