P-142: 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

<h3>Background</h3> 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, has been approved for MT because of the convenience and tolerability. 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. <h3>Method</h3> 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 MT. 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. The primary endpoint was PFS from MT. <h3>Results</h3> A total of 111 patients were enrolled, including 45 in I-MT, 41 in L-MT and 25 in IL-MT. The demographic and clinical characteristics were comparable among three groups at baseline, including gender ratio, age, paraprotein isotype, ISS, R-ISS, response status before MT, and ASCT rate. Patients on IL-MT were slightly younger. The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were comparable. The median follow-up duration since MT was 5.9, 13.5 and 5.3 months in I-MT, L-MT and IL-MT group, respectively. Disease progression rate was 4.4%, 12.2% and 8%. Mortality rate was 2.2%, 2.4% and 0. There were 84%, 88.8% and 80% of the patients reached VGPR or better before MT, while the rates improved to 95%, 84% and 92% during follow-up. The prevalence of peripheral neuropathy with grade 1 was 20% on I-MT, 36% on IL-MT and 4.9% on L-MT. No grade 2 PN or higher was recorded. The incidence of gastrointestinal events was 11.1%, 24% and 0, respectively. All hematologic toxicities were lower than 8%. Infection rates were 8.9%, 4% and 7.3%. Skin rashes were more common in lenalidomide containing regimens (2.2%, 8% and 7.3%). No drug withdrawal was related to adverse events. <h3>Conclusion</h3> Due to inadequate access to melphalan and low rate of ASCT in China, there is still a gap of PFS in NDMM patients with those in western countries. We herein 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.