KEY TAKEAWAYS
- The study aimed to compare the efficacy and tolerability of I-MT or IL-MT to L-MT as a maintenance regimen for transplant-ineligible NDMM patients.
- NDMM patients who achieved at least a partial response (PR) after 5 to 9 cycles of first-line chemotherapy were enrolled in the study.
- After adjusting for various factors, the data suggested that L-MT was associated with significantly longer PFS than I-MT.
Maintenance therapy (MT) enhances response and prolongs progression-free survival (PFS) in newly diagnosed multiple myeloma (NDMM) patients treated with frontline therapies. Ixazomib, an oral proteasome inhibitor (PI) of the second generation, has been approved for MT due to its convenience and tolerability. This prospective, multicenter study was conducted to compare the efficacy and tolerability of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as a maintenance regimen for transplant-ineligibleNDMM patients.
Since September 2019, NDMM patients from 10 North China MM Registry centers have been enrolled. Patients receiving between 5 and 9 cycles of first-line chemotherapy and achieving at least a partial response (PR) began MT. If PR was not reached after four cycles, a second-line induction of 2 to 5 processes was administered until PR was achieved. Ixazomib 4 mg was administered on days 1, 8, and 15. In a 28-day regimen, lenalidomide 25 mg was administered every other day from day 1 to day 21. Patients in the dual drug group received the doses of Ixazomib and Lenalidomide indicated above. The primary outcome measure was progression-free survival (PFS) in patients with MT.
There were 181 patients enrolled, 70 in I-MT, 63 in L-MT, and 48 in IL-MT. The demographic and clinical characteristics, such as gender ratio, age, paraprotein isotype, international staging system (ISS), and revised ISS (R-ISS), were comparable between the various MT regimen groups. In the IL-MT group, the proportions of deletion 17p,t(4,14), and t(14,16) were marginally higher. Since maintenance, the median follow-up duration for I-MT, L-MT, and IL-MT was 23.9, 24.0, and 18.9 months, respectively. About 74%, 79%, and 81% of patients achieved VGPR or more extraordinary before MT. At the same time, the rates of deep responses improved to 82.9%, 81.0%, and 89.9% during follow-up. In 37.2% (N=26) of patients on I-MT, 19.0% (N=12) on L-MT, and 29.2% (N=14) on IL-MT, respectively, progressive disease (PD) was observed. The median PFS was 25.5m, not reached (NR), and 22.8m, whereas OS was not achieved in any groups. After adjusting for age, high-risk cytogenetics, ISS, front-line induction regimens, and depth of response before maintenance by Cox model multivariate analysis, researcher’s data suggested that L-MT was associated with significantly longer PFS compared to I-MT (P=0.023, HR=0.39). In contrast, PFS in the IL-MT group was comparable to that of the other two groups (P=0.22, HR=0.66). As for safety, the incidence of peripheral neuropathy was 15.7% for I-MT, 15.7% for L-MT, and 18.8% for IL-MT in the entire cohort. The incidence of digestive disorders was 24.3%, 1.6%, and 22.9%, respectively. Patients developed hematologic toxicity at 5.7%, 9.5%, and 10.4%, respectively. Infections were noted in 10%, 3.2%, and 2.0% of patients. The I-MT group lost three patients due to adverse events. In the L-MT and IL-MT groups, zero and two patients changed their MT regimen due to intolerance. This prospective multi-center study is designed to determine whether dual drug maintenance will improve response in non-transplant NDMM patients. The researcher’s preliminary findings indicate that more clinicians in actual practice are inclined to prescribe IL-MT to high-risk patients. Although tolerable, whether dual-drug maintenance will improve survival remains to be determined.
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04217967
Zhe Zhuang, Ying Tian, Lei Shi, Hong Yu, Qinhua Liu, Dongmei Zou, Weiwei Tian, Ru Feng, Fei Dong, Yanping Ma, Shuangjiao Liu, Hongmei Jing, Hui Liu, Liangming Ma, Wanling Sun, Rong Fu, Li Bao, Yin Wu, Wenming Chen, Junling Zhuang/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/Inc, M. G. (n.d.). IXAZOMIB VERSUS LENALIDOMIDE OR IXAZOMIB AND LENALIDOMIDE… by Junling Zhuang. Library.ehaweb.org. Retrieved July 15, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386702/junling.zhuang.ixazomib.versus.lenalidomide.or.ixazomib.and.lenalidomide.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
