Real-World Experience with Elotuzumab, Pomalidomide, and Dexamethasone As Second or Third-Line Therapy in Relapsed and Refractory Multiple Myeloma

Background: Elotuzumab, an IgG1 monoclonal antibody directed against signaling lymphocytic activation molecule F7 (SLAMF7), has demonstrated efficacy in the treatment of relapsed/refractory multiple myeloma (RRMM). In a phase III trial comparing elotuzumab, pomalidomide, and dexamethasone (EPd) to pomalidomide and dexamethasone alone in patients with RRMM after two or more prior lines of therapy, EPd showed progression-free (PFS) and overall survival (OS) benefit. Given the lack of evidence regarding outcomes with EPd in a real-world population, we aimed to evaluate the outcomes of patients with RRMM treated with EPd at a large academic center in the United States.

Methods: We conducted a retrospective study of patients with RRMM given EPd as second or third-line therapy between July 2017 and July 2023. Pharmacy records were utilized to identify patients who had completed at least one 28-day cycle of EPd, with treatment being continued until progression or unacceptable toxicity. EMR was reviewed to collect baseline characteristics. High risk (HR) cytogenetics were defined as t(4:14), t(14:16), t(14:20), or del(17p); double hit (DH) cytogenetics were defined as two HR changes or one HR change with gain(1q). Disease risk was classified using the second revision of the International Staging System (R2-ISS). Response was graded per International Myeloma Working Group criteria. PFS and OS from EPd treatment initiation were calculated using the Kaplan-Meier method, and differences in PFS between subgroups were calculated using a log-rank test.

Results: Among the 28 eligible patients, the average age at diagnosis was 62. Sixty-four percent of patients were White, 25% were Black, and 71% were female. HR cytogenetics were present in 29% and DH cytogenetics in 21% of patients, and 64% of patients (n=25) were classified as R2-ISS stages Intermediate-High (III) or High Risk (IV). The M-protein isotypes were 57% IgG, 14% IgA, and 6% FLC, with light chains being 68% kappa and 32% lambda.

Fifty-four percent of patients received EPd as second-line and 46% as third-line therapy. Biochemical progression was seen in 82% of patients prior to EPd. In regard to prior drug exposure, 96% of patients were treated with lenalidomide, 75% with bortezomib, 29% with daratumumab, and 5% with pomalidomide. Sixty-one percent of patients had a prior autologous stem cell transplant. The overall response rate (ORR) was 46%, with 21% achieving very good partial response (VGPR) and 14% achieving complete response (CR). The estimated 1-year PFS was 43% [95% CI: 23 - 63%] and the median PFS was 223 days [95% CI: 52 - 394].

To further understand the optimal population for this regimen, we performed subgroup analyses of disease response and PFS with the following variables: EPd line number, R2-ISS (Stage III/IV vs. I/II), HR and DH cytogenetics. ORR was similar in second vs. third-line therapy (47% vs. 46%) and high vs. low R2-ISS stage (55.6% vs. 50%). ORR was 25% in patients with HR cytogenetics compared to 55% without; ORR in patients with DH cytogenetics was 17% compared to 55% without. The median PFS for second vs. third-line therapy was similar (223 vs. 140 days, p = 0.68). The median PFS for high vs. low R2-ISS stage was 63 days compared to 473 days (p = 0.21). The median PFS for HR vs. standard risk cytogenetics was 141 vs. 434 days (p = 0.18). DH cytogenetics trended also towards a lower median PFS (84 vs. 434 days, p = 0.06).

Conclusion: In this real-world cohort, no substantial differences were found in PFS and ORR between second and third-line EPd. However, while not statistically significant, patients with HR and DH cytogenetics trended towards lower ORR and PFS, and patients with R2-ISS III/IV trended towards lower PFS, suggesting that EPd may be suboptimal in these patients. Although this study is limited by small sample size, it suggests a need to further optimize EPd usage in RRMM.

Schroeder:Incyte: Honoraria; Kura Oncology: Honoraria; Advarra: Honoraria. Vij:Sanofi, BMS, Takeda: Other, Patents & Royalties; Janssen, Pfizer, GSK, Regeneron, Karyopharm: Other, Patents & Royalties.