(OA-54) Efficacy of Mezigdomide Plus Dexamethasone and Bortezomib or Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma by Line of Therapy: Results from the Phase 1/2 CC-92480-MM-002 Trial

Mezigdomide (MEZI) is an oral CELMoD™ agent with antitumor and immunostimulatory therapeutic effects that has shown promising activity in combination with dexamethasone (DEX) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM) (Richardson P, et al. N Engl J Med 2023;389:1009–1022). Here we report efficacy data by number of prior lines of therapy (LOTs) among patients with RRMM who were treated with MEZI plus bortezomib and DEX (MeziVd) or MEZI plus carfilzomib and DEX (MeziKd) in the phase 1/2 CC-92480-MM-002 trial (NCT03989414, EUCT 2023-505219-19).

Methods:

Adult patients with RRMM received 0.3, 0.6, or 1.0 mg oral MEZI on days 1–14 of each 21-day cycle plus subcutaneous bortezomib and oral DEX (MeziVd; dose-escalation cohort A, N = 28); 0.6 or 1.0 mg oral MEZI on days 1–14 of each 21-day cycle plus subcutaneous bortezomib and oral DEX (MeziVd; dose-expansion cohort D, N = 49); or 0.3, 0.6, or 1.0 mg oral MEZI on days 1–21 of each 28-day cycle plus intravenous carfilzomib and oral DEX (MeziKd; dose-escalation cohort C, N = 27). All patients had received prior lenalidomide (≥ 2 consecutive cycles). The primary objectives of the trial were to determine the recommended dose and regimen of MEZI and to evaluate safety and preliminary efficacy.

Results:

Patients in cohorts A, D, and C (N = 104) had received 1 (n = 31), 2 (n = 43), 3 (n = 23), or 4 (n = 7) prior LOTs. Prior LOTs included immunomodulatory drug (IMiD^®) agents (100%), proteasome inhibitors (94.2%), and anti-CD38 monoclonal antibodies (52.8%). Median (range) follow-up for progression-free survival (PFS) was 16.6 mo (1.2–42.2), 12.3 mo (1.0–38.0), 9.0 mo (0.7–60.4), and 9.2 mo (1.5–13.8) among patients with 1, 2, 3, and 4 prior LOTs, respectively. Overall response rates were >70% regardless of the number of prior LOTs: 1 LOT, 83.9% (n = 26); 2 LOTs, 88.4% (n = 38); 3 LOTs, 73.9% (n = 17); 4 LOTs, 71.4% (n = 5). Complete response (CR) or better was observed in 8 (25.8%), 11 (25.6%), and 2 (8.7%) patients with 1, 2, and 3 prior LOTs, respectively; no patients with 4 prior LOTs achieved CR or better. Median (95% confidence interval) PFS was 19.4 mo (10.0–not reached), 12.9 mo (10.2–20.1), 13.0 mo (5.8–31.6), and 9.2 mo (1.5–11.8) among patients with 1, 2, 3, and 4 prior LOTs, respectively; PFS rates (standard error) at 12 mo were 64.1% (9.2), 54.3% (7.8), 58.3% (10.8), and 14.3% (13.2), respectively.
 


Conclusions:

In this population of patients with RRMM, many were previously exposed to IMiD agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies; a majority of patients treated with MeziVd or MeziKd achieved PR or better, regardless of the number of prior LOTs. Patients receiving up to 3 prior LOTs experienced durable PFS, with median PFS > 1 year in each group and 19.4 mo for patients with 1 prior LOT. These data support further investigation of MeziVd and MeziKd in the phase 3 SUCCESSOR-1 (NCT05519085) and SUCCESSOR-2 (NCT05552976) clinical trials.