Addition of Elotuzumab Prolongs Survival in Relapsed or Refractory Myeloma

Treatment with elotuzumab plus lenalidomide and dexamethasone (ERd) was associated with significant and clinically meaningful reductions in mortality risk, compared with lenalidomide and dexamethasone alone (Rd), in patients with relapsed or refractory multiple myeloma (MM), according to results from the phase III ELOQUENT-2 trial. The survival benefit was particularly evident in older patients and patients with high-risk disease, lead author Meletios Dimopoulos, MD, of the National and Kapodistrian University of Athens School of Medicine in Greece, told ASH Clinical News.

“At the time of study design, Rd was the standard of care for patients with relapsed or refractory MM,” Dr. Dimopoulos said. “The ERd triplet not only showed a long-standing improvement in progression-free survival [PFS], but also in overall survival [OS].”

The ELOQUENT-2 study evaluated the efficacy and safety of ERd compared with Rd in patients with relapsed or refractory MM who had received between 1 and 3 prior lines of therapy. The trial enrolled 635 participants who were randomized to receive either ERd (n=318) or Rd (n=317). PFS and overall response rate (ORR) were the primary endpoints and OS was a key secondary endpoint of the study, with the final OS analysis planned after 427 deaths.

In the overall cohort, the median age was 66 years (range = 37-91), and 20% of patients were 75 years or older. Approximately one-fifth of patients in each group had International Staging System stage III disease, and 35% of patients in each arm were refractory to their last treatment.

After a minimum follow-up period of 70.6 months, which the authors noted was the longest reported to date for an antibody-based triplet in this setting, a slightly higher proportion of patients in the ERd arm remained on treatment, compared with patients in the Rd arm (10% and 4%). The most common reasons for discontinuation included disease progression (56% and 57%) and study drug toxicity (12% and 14%).

At the time of the final OS analysis, there were 212 deaths in the ERd group (66%) and 225 deaths in the RD arm (69%). The median OS was roughly 8.7 months longer with ERd compared with Rd (48.3 vs. 39.6 months, respectively; hazard ratio [HR] = 0.82; 95% Cl 0.68-1.00; p=0.04).

The investigators observed an early separation of OS curves at 1 year after trial enrollment (91% with ERd and 83% with Rd), which continued at 2 years (73% vs. 69%), 3 years (60% vs. 53%), and 4 years (50% vs. 43%). Overall, treatment with ERd was associated with an 18% reduction in the risk of death compared with Rd.

“The good tolerability of ERd makes it attractive for elderly patients and for patients who had a long progression-free survival before treatment with this combination.”

—Meletios Dimopoulos, MD

An OS benefit was also identified in specific subgroups. For instance, the median OS was 17.4 months longer with ERd in patients who had received between 2 and 3 prior lines of treatment (51.0 vs. 33.6 months; HR=0.71; 95% CI 0.54-0.92). The median OS was also longer in patients treated with ERd across certain age groups:

  • ≥75 years: 48.5 vs. 27.4 months (HR= 0.69; 95% CI 0.46-1.03)
  • <75 years: 47.9 vs. 43.7 months (HR=0.86; 95% CI 0.70-1.06)
  • <65 years: 63.5 vs. 47.7 months (HR=0.70; 95% CI 0.52-0.96)

In a subgroup of patients who were refractory to their most recent treatment, including 113 patients in the ERd group and 114 patients in the Rd group, treatment with ERd was associated with a 14.5-month longer OS compared with Rd (40.4 vs. 25.9 months; HR=0.67; 95% CI 0.49-0.91). The OS benefit with elotuzumab also was seen in the subgroup of patients with relapsed disease: Patients in the ERd group had median OS of 51.2 months, compared with 47.7 months in the Rd-alone group (HR=0.93; 95% CI 0.73-1.18).

Patients with high-risk or more advanced disease also had longer OS with elotuzumab treatment (TABLE).

No new safety signals with elotuzumab were identified in the extended follow-up, and the most common adverse events of interest included infections (84%), renal and urinary disorders (27%), cardiac disorders (24%), and pneumonia (22%). Dr. Dimopoulos added, “The good tolerability of the combination makes it attractive for elderly patients and for patients who had a long PFS before the treatment with ERd,” he said.

A limitation of this study, according to the investigators, is that the prior therapy participants received may not have reflected that used in current clinical practice, as the treatment landscape for myeloma has changed since the trial first started enrolling and dosing patients. Dr. Dimopoulos also noted a limitation of ERd: the activity of this triplet combination may be less pronounced compared with combinations that include anti-CD38 monoclonal antibodies such as daratumumab.

Study authors report relationships with Bristol Myers Squibb and AbbVie, which sponsored this trial.

Reference

Dimopoulos MA, Lonial S, White D, et al. Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study. Blood Cancer J. 2020;10:91.