Safety and Survival Outcomes in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated with Lenalidomide-Based or Non-Lenalidomide-Based Treatments in the Real-World MM-034 Study

Introduction Lenalidomide (LEN)-based treatment is standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma (TNE NDMM). The FIRST and SWOG S0777 trials showed safety and efficacy of LEN in TNE NDMM. We present an update to the ongoing, non-interventional, post-authorization MM-034 study (NCT03106324), which assesses the safety of LEN-based treatment (including LEN+dexamethasone [Rd] and Rd+bortezomib [RVd]) or non-LEN treatment (including bortezomib+melphalan/prednisone [VMP]) in patients with TNE NDMM.

Methods Patients with TNE NDMM initiating or with < 2 cycles of first-line treatment were eligible. Patients were recruited from 12 countries in Europe and followed for 5 years (≤ 3 years on treatment). Incidence of cardiac events (CEs) was the primary endpoint. Secondary endpoints included safety, infections, and second primary malignancies (SPMs). In this analysis, duration of treatment (DoT), dose adjustments, and Kaplan-Meier estimates for overall survival (OS) were also assessed.

Results A total of 452 patients on LEN-based treatment (Rd, 382; RVd, 49) and 440 on non-LEN treatment (VMP, 278) were enrolled. Median (range) follow-up was 20.4 (0.3-50.0) months for LEN (Rd, 20.3 [0.3-50.0]; RVd, 21.4 [1.0-42.0]) and 15.7 (0.2-55.5) months for non-LEN (VMP, 16.1 [0.8-46.6]). In the LEN cohort, 304 (67.3%) patients discontinued treatment, 93 (20.6%) due to adverse events (AEs). In non-LEN, 401 (91.1%) patients discontinued, 69 (15.7%) due to AEs. CEs occurred in 63 (13.9%) patients in LEN and 52 (11.8%) in non-LEN. There was 1 SPM in LEN and 0 in non-LEN. In LEN, 249 (55.1%) patients had ≥ 1 dose adjustment (Rd, 208 [54.5%]; RVd, 33 [67.3%]) vs 260 (59.1%) in non-LEN (VMP, 184 [66.2%]). Median DoT (mDoT) was 10.8 months for LEN (Rd, 10.8; RVd, 11.1) and 8.0 months for non-LEN (VMP, 9.8). In patients with ≥ 1 dose adjustment, mDoT was 15.0 months for LEN (Rd, 15.2; RVd, 11.7) and 9.7 months for non-LEN (VMP, 10.1). In all other patients, mDoT was 4.9 months for LEN (Rd, 4.9; RVd, 4.4) and 5.6 months for non-LEN (VMP, 6.8). Median OS (mOS) (95% confidence interval [CI]) was 41.0 (31.4-not reached [NR]) months in LEN (including Rd and RVd) and 24.8 (22.4-27.8) months in non-LEN (including VMP). In patients who discontinued treatment due to AEs, mOS (95% CI) was 21.9 (20.5-28.7) months in LEN (including Rd and RVd) and 22.1 (18.4-25.6) months in non-LEN (including VMP). In all other patients, mOS (95% CI) was NR in LEN (including Rd and RVd) and 26.9 (23.3-30.5) months in non-LEN (including VMP).

Conclusions The safety profile of LEN-based treatment in patients with TNE NDMM was consistent with that previously reported, with no new safety signals identified. More patients in non-LEN discontinued treatment than in LEN. Patients who had ≥ 1 dose adjustment had longer mDoT than those who did not, but this did not account for any differences in disease severity. While the LEN cohort had mOS almost twice that of non-LEN, patients who discontinued LEN due to AEs had a shorter mOS than the entire LEN cohort. Treatment tolerability is an important consideration in improving patient outcomes.

Study support This study was supported by Bristol Myers Squibb.

Cavo:AbbVie, Amgen, Bristol Myers Squibb/Celgene, Pfizer, GlaxoSmithKline, Sanofi, Roche, Takeda: Consultancy, Honoraria; Janssen: Honoraria, Speakers Bureau. Dhanasiri:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. De Stefano:AbbVie: Honoraria; Amgen: Honoraria, Speakers Bureau; Bristol Myers Squibb/Celgene: Honoraria, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gil:Bristol Myers Squibb: Other: Contractor. Bernasconi:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Gamberi:Amgen, Bristol Myers Squibb, Janssen, GlaxoSmithKline: Honoraria; Takeda, Bristol Myers Squibb, GlaxoSmithKline, Sanofi, Janssen, Amgen: Other: Advisory board.