P978: IXAZOMIB VERSUS LENALIDOMIDE OR IXAZOMIB AND LENALIDOMIDE COMBINATION AS MAINTENANCE REGIMEN FOR PATIENTS WITH MULTIPLE MYELOMA: INTERIM ANALYSIS OF A MULTI-CENTER PROSPECTIVE STUDY IN CHINA

Abstract

Background: Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2nd generation oral proteasome inhibitor (PI), has been approved for MT because of its convenience and tolerability. Aims: We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimen in NDMM patients. Methods: This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry since September 2019. After 4 cycles of front-line induction therapy, patients reached partial response (PR) would receive autologous stem cell transplantation (ASCT) if eligible, or keep up to 5 cycles of front regimens if ineligible, then start maintenance therapy. Patients did not reach PR would switch to 2nd-line induction for 2-5 cycles and start MT once PR was achieved. For MT, 4mg of Ixazomib was given on day 1,8,15, and 25mg of Lenalidomide every other day on days 1–21 of 28day cycles. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was PFS from MT. Results: A total of 176 patients were enrolled, including 58 in I-MT, 72 in L-MT and 46 in IL-MT. The demographic and clinical characteristics, including gender ratio, age, paraprotein isotype, ISS, R-ISS, were comparable among different MT regimen groups either receiving ASCT or not at baseline (Table 1). The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were lower in L-MT without ASCT and I-MT with ASCT. The median follow-up duration since MT was 10.6, 12.6 and 11.1 months in I-MT, L-MT and IL-MT groups in non-ASCT patients, while 9.3, 14.0 and 12.2 months in ASCT patients, respectively. In non-ASCT groups, the disease progression rates were 13.5%, 10.2% and 10.8%, whereas 0, 21.7% and 0 in ASCT groups. The median PFS and OS were not reached (NR) in all groups. There were 73.1%, 73.4% and 78.3% of the patients reached VGPR or better before MT in non-ASCT patients, while the rates improved to 80.8%, 81.6% and 86.5% during follow-up. The depth of response did not change in ASCT patients. In the whole cohort, the prevalence of peripheral neuropathy (PN) was 18.9% on I-MT, 8.3% on L-MT and 21.7% on IL-MT. Grade 2 PN occurred in 3, 0 and 2 patients, respectively. The incidence of gastrointestinal (GI) events was 12.1%, 1.4% and 15.2%, respectively. Grade 3 GI events occurred in 3, 0 and 1 patients. The incidence of grade 3-4 hematologic toxicities was 1.7%, 4.2%, and 2.2%. Infections developed in 10.3%, 2.8% and 4.3% patients. No drug withdrawal was related to adverse events. Image:Summary/Conclusion: Due to inadequate access to melphalan and low rate of ASCT, the PFS of NDMM in Chinese patients was relatively inferior. We design this multi-centered prospective study to evaluate if dual drug MT will further strengthen response and make up the gap. Though the primary endpoint--PFS has not been reached in all treatment groups, dual MT improves response most and is quite tolerable.