PB2038: LENALIDOMIDE OR BORTEZOMIB AS MAINTENANCE TREATMENT OVERCOMES INFERIOR IMPACT OF HIGH-RISK CYTOGENETIC ABNORMALITIES IN TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA IN CHINA

Abstract

Background: Maintenance (MT) after front-line therapy is recommended in guidelines for multiple myeloma. However, no adequate data has shown the current situation of MT in China yet, especially in transplant-ineligible patients with newly diagnosed MM (NDMM). Aims: We conducted this retrospective real-world study on efficacy and safety of the mainstream maintenance regimens in non-transplant NDMM patients—lenalidomide (L-MT), bortezomib (B-MT) and thalidomide (T-MT). Methods: Clinical data were collected from 11 centers of North China MM Registry from January 2010 to July 2021. Patients achieving partial remission (PR) or better after induction therapy were included. The progression-free (PFS) and overall survival (OS) from MT, and drug toxicities were compared in L-MT, B-MT and T-MT groups. Thalidomide 75-150mg/day was administrated in T-MT group. L-MT group received lenalidomide as 25mg every other day or 10mg daily, on days 1–21 in a 28-day cycle. Bortezomib (1.3 mg/m2 s.c.) was administered every 2 weeks or 4 vials every 3 months. Dexamethasone was given along with T, L or B in some patients. Results: A total of 350 patients were enrolled including 155 in T-MT, 141 in L-MT and 54 in B-MT. At baseline, the gender ratio, paraprotein isotype, ISS and R-ISS stage were comparable. Patients on L-MT were significantly older than the other groups. Meanwhile, greater proportions of patients in L-MT and B-MT group had high-risk cytogenetic abnormalities (HRCA), defined as amplification 1q21, deletion 17p, t(4,14), t(14,16). The median follow-up duration since maintenance was 42.5, 22.0 and 26.4 months (m) in T-MT, L-MT and B-MT groups, respectively. Disease progression was recorded in 101 patients (65.2%) with T-MT, 58 (41.1%) with L-MT and 22(40.7%) with B-MT. While mortality was 51(32.9%), 23(16.3%) and 5(9.3%), respectively. The median PFS was 23.7m in T-MT, as compared with 27.4m in L-MT and 29.7m in B-MT (p=0.52). Median OS was 90.7m in T-MT, whereas not reached (NR) in L-MT and B-MT groups (p=0.46). Patients achieving complete response (CR) or stringent CR (sCR) before MT had prolonged PFS compared to those with VGPR or less in T-MT (40.1m vs 17.2m, p＜0.01), while comparable in L-MT (27.4m vs 26.9m, p=0.09) or B-MT group (NR vs 29.7m, p=0.34). Meanwhile, patients in each group had similar OS despite of different response before MT, their PFS and OS were also comparable despite of different induction regimens. Long-term duration of maintenance which was defined as over 24 months translated into significant better PFS in all groups (T-MT 57.2m vs 12.1m, L-MT 54.3m vs 19.2m, B-MT 37.3m vs 16.7m, p＜0.01), as well as better OS. For patients with high-risk cytogenetic abnormalities, T-MT resulted in impaired PFS (12.2m vs 21.2m, p=0.04) and OS (54.9m vs NR, p＜0.01). In contrast, PFS and OS were both comparable in patients with L-MT or B-MT no matter with HRCA or not. The main reason of maintenance withdrawal was disease progression. Adverse event related discontinuation was seen in 8.5%, 5.1% and 8.3% of the patients in T-MT, L-MT and B-MT, respectively. Image:Summary/Conclusion: In this multi-centered real-world maintenance study, thalidomide, lenalidomide or bortezomib after front-line therapy in non-transplant patients with NDMM has similar PFS and OS. However, patients on L-MT and B-MT have greater proportion of HRCAs, which drags down survival in T-MT, while L-MT and B-MT reverses the negative effect. Clinicians in the real practice prefer to select lenalidomide or bortezomib as maintenance in patients with HRCAs, while thalidomide is still an option for patients with standard risk.