Patients with Newly Diagnosed Transplant-Eligible MM and Minimal Residual Disease after Treatment with Ixazomib, Lenalidomide, and Dexamethasone

2020 Year in Review - Multiple Myeloma

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.

Reference
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.

Related Items


Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: