P-125: Ixazomib versus Lenalidomide or Ixazomib and Lenalidomide combination as maintenance regimen for transplant-ineligible multiple myeloma: update of a multi-center prospective study in China

Introduction: 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 due to 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 transplant-ineligible 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. Patients receiving up to 5-9 cycles of front-line regimens and reaching at least partial response (PR) started MT. If PR was not reached after 4 cycles, 2nd-line induction for 2-5 cycles would be conducted till PR was reached. Ixazomib 4mg was given on day 1,8,15. Lenalidomide 25mg was given every other day on days 1–21 in a 28-day cycle. Patients in dual-drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was progression free survival (PFS) from MT.

Results: A total of 200 patients were enrolled, including 74 in I-MT, 76 in L-MT and 50 in IL-MT. Patients in L-MT group was younger than those in I-MT and IL-MT group (median age of 61.0±8.1ys, vs 65.2±8.5ys and 63.5±8.3ys, respectively, p=0.03). The proportion of deletion 17p was slightly higher in IL-MT group. While other baseline characteristics, including gender ratio, paraprotein isotype, international staging system (ISS), revised-ISS (R-ISS), were comparable among different MT regimen groups.
The median follow-up duration since maintenance was 27, 28 and 23 months in I-MT, L-MT and IL-MT, respectively. There were 75.6%, 80.3% and 80% of the patients reached very good remission (VGPR) or better before MT, while the rates of deep responses improved to 85.1%, 87.1% and 88% during follow-up. Progressive disease (PD) was recorded in 46.7% (N=32) of patients on I-MT, 31.6% (N=24) on L-MT and 36% (N=18) on IL-MT, respectively. The median PFS was 29.3m, not reached (NR) and 22.9m, while OS was not reached in all groups. Cox model multivariate analysis suggested that I-MT and IL-MT provided similar PFS to that of L-MT (HR 95% CI 0.57-1.95, p=0.87; and HR 95% CI 0.56-1.96, p=0.87; respectively).
The main reason of MT withdrawal was disease progression. Adverse event related discontinuation was 8.3%, 0% and 20%, respectively.

Conclusions: We design this multi-centered prospective study to evaluate whether dual drug maintenance will further strengthen response in non-transplant NDMM patients. Our preliminary data suggest that more clinicians in the real practice are inclined to prescribe IL-MT for high-risk patients. Whether dual-drug maintenance will provide better survival still needs to be defined.