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ELOQUENT-3: Elotuzumab plus pomalidomide/dexamethasone (EPd) shows favorable results over Pd for treatment of relapsed/refractory multiple myeloma

Pomalidomide plus dexamethasone is indicated for patients previously treated with lenalidomide and a proteasome inhibitor. The phase II ELOQUENT-3 study investigated the hypothesized synergistic effect of elotuzumab and pomalidomide as was previously found for elotuzumab and lenalidomide. EPd showed a 46% reduction in risk of progression or death versus Pd. Median PFS was 10.3 months with EPd, and 4.7 months with Pd. Safety was consistent with prior reports of elotuzumab and pomalidomide. These results suggest that for patients with relapsed/refractory multiple myeloma who have failed lenalidomide and a proteasome inhibitor, EPd may be a new treatment option.

Disease control of relapsed/refractory multiple myeloma (RRMM) remains poor. The SLAMF7-directed, immunostimulatory monoclonal antibody elotuzumab (elo) plus lenalidomide (len)/dexamethasone (dex) showed sustained progression-free survival (PFS) benefits and acceptable safety in patients with RRMM in the phase 3 ELOQUENT-2 study. The immunomodulatory drug pomalidomide (pom) plus dex (Pd) is indicated for RRMM patients previously treated with lenalidomide and a proteasome inhibitor (PI). Goal in the phase 2 ELOQUENT-3 study was to compare the efficacy and safety of EPd versus Pd in patients with RRMM.

Patients with ≥2 prior lines of therapy including len and a PI (pom not permitted), who were refractory to last therapy and either refractory or relapsed and refractory to len and a PI were randomized 1:1 to EPd or Pd and treated in 28-day cycles until disease progression or unacceptable toxicity. Elo: 10 mg/kg IV weekly in cycles 1–2 and 20 mg/kg IV every 4 weeks thereafter. Pom: 4 mg orally on D 1–21 of each cycle. Dex: 40 or 20 mg equivalent weekly for patients ≤75 y or >75 y, respectively. Primary endpoint was investigator-assessed PFS.

Of 117 patients, 60 were randomized to EPd and 57 to Pd. Median age was 67 year; median (range) number of prior lines of therapy was 3 (2–8). Prior therapies included bortezomib (100%), len (99%), carfilzomib (21%), ixazomib (6%), daratumumab (3%), and stem cell transplantation (55%). 87% of patients were refractory to len, 80% to a PI, and 70% to both. At database lock (Feb 21, 2018; minimum follow-up 9.1 months), 40% (24/60) and 20% (11/55) of treated patients remained on EPd and Pd. Disease progression (EPd 43% versus Pd 56%) was the main reason for discontinuation. EPd showed a 46% reduction in risk of progression or death versus Pd (hazard ratio 0.54; 95% CI 0.34–0.86; p=0.0078). Median PFS (95% CI) was 10.3 months (5.6–not estimable) with EPd, and 4.7 months (2.8–7.2) with Pd. ORR (95% CI) was 53% (40–66) with EPd versus 26% (16–40) with Pd (odds ratio 3.25; 95% CI 1.49–7.11; p=0.0029). Very good partial response or better was seen in 20% (EPd) versus 9% (Pd) of patients. Immature OS suggested a trend in favor of EPd.

Adverse events (AEs; not exposure adjusted) of grade 3-4 neutropenia (EPd 13% versus Pd 27%) and anemia (10% versus 20%) were lower with EPd, despite longer exposure (median number of cycles 9 versus 5) and similar dose intensity of pom between arms. Any-grade infections occurred in 65% of patients in both arms. Infusion reactions occurred in 3 (5%) patients with elo; all were grade 1–2 and manageable. AEs led to discontinuation in 18% (EPd) versus 24% (Pd) of patient. Deaths (EPd 13 versus Pd 18) were mostly due to disease progression (13% versus 25% of treated patients).

In summary, this first randomized trial of elo plus Pd for RRMM, EPd showed a clinically meaningful and highly significant 46% reduction in risk of progression or death versus Pd. More patients remained on EPd versus Pd at cutoff date, and safety was consistent with prior reports of elo and pom. These data suggest that EPd may be a new treatment option for patients with RRMM who have failed len and a PI.

 

Reference

Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide/dexamethasone (EPd) versus Pd for treatment of relapsed/refractory multiple myeloma: results from the phase 2, randomized open-label ELOQUENT-3 study. Presented at EHA 2018; abstract LB2606.

Speaker Meletios Dimopoulos

Dimopoulos

Prof. Meletios Dimopoulos, MD, National and Kapodistrian University of Athens, Athens, Greece

 

See: Keyslides

 

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