A three-year follow-up of the ELOQUENT-2 study compared the long-term safety of elotuzumab—a humanized immunoglobulin G1 monoclonal antibody—in combination with lenalidomide and dexamethasone (ELd) versus lenalidomide and dexamethasone (Ld) alone in patients with relapsed/refractory multiple myeloma (MM). This ongoing phase III, open-label, randomized, multicenter study included patients who had received one to three previous lines of therapy and assessed the safety of each treatment regimen. 

Deborah Doss, RN, OCN®, Kathleen Colson, RN, BSN, BS, Charise Gleason, MSN, NP-BC, AOCNP®, Sagar Lonial, MD, and Paul G. Richardson, MD, presented the findings during a poster session at the ONS 41st Annual Congress in San Antonio, TX. The poster was titled “Elotuzumab in Combination With Lenalidomide/Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma (ELOQUENT-2): A 3-Year Safety Update.” The study was funded by Bristol-Myers Squibb and AbbVie Biotherapeutics.

The study began in June 2011 and the long-term results were analyzed through August 2015. At the extended follow-up, prespecified interim analysis for overall survival indicated a trend in favor of ELd over Ld (hazard ratio = 0.77; p = 0.001).

Table 1. Myeloma-Related Clinically Important Adverse Events of Any Grade

Adverse Event ELd (n=321)  Ld (n=325)
Gastrointestinal disorders 81% 68%
Repiratory disorders 63% 53%
Renal/urinary disorders 25% 18%
Peripheral neuropathy 15% 9%
Hypertension 10% 7%
Deep vein thrombosis 8% 4%
Cardiac failure 1% 2%
ELd = elotuzumab/lenalidomide/dexamethasone; Ld = lenalidomide/dexamethasone

 

Patients were eligible for inclusion if they had an Eastern Cooperative Oncology Group performance status of 0–2. Patients were excluded if they had active plasma cell leukemia, significant cardiac disease, had experienced adverse events of any prior chemotherapy, surgery, or radiotherapy not resolved to less than grade 2, and non-secretory, oligo-secretory, or serum free light chain-only myeloma.

The 646 patients were randomized to receive

  • Lenalidomide 25 mg taken orally twice daily on days 1–21 and dexamethasone 40 mg taken orally twice daily once a week (Ld; n = 325)
  • Ld regimen plus elotuzumab 10 mg/kg administered via IV weekly during cycles 1 and 2 then every other week thereafter (ELd; n = 321).

The median patient age was 66 years, and patients had received a median of two prior therapies (range = 1–4). 

Among patients in the ELd treatment cohort, 10% experienced infusion reactions (IRs), of which 9% were grade 1 or 2 and 1% was grade 3. The most common IRs were pyrexia (3%), chills (1%), and hypertension (1%). No grade 4 or 5 IRs were reported in the ELd group. Treatment was disrupted in 5% of the ELd cohort because of an IR, with two patient discontinuing treatment.

Exposure-adjusted infection rates were 198 in the ELd cohort and 192 in the Ld group.

Grade 3 or 4 adverse events (AEs) were reported in 78% of the ELd cohort (n = 248) compared with 67% of the Ld group (n = 212). Any grade non-hematologic AEs that occurred in the ELd and Ld cohorts included fatigue (48% versus 40%), diarrhea (48% versus 37%), pyrexia (38% versus 25%), constipation (36% versus 28%), cough (33% versus 19%), and muscle spasms (30% versus 27%). Any grade hematologic AEs that occurred in the ELd and Ld cohorts included anemia (41% versus 37%) and neutropenia (34% versus 43%).

See Table 1 for myeloma-related AEs of clinical importance.

“Elotuzumab, in combination with Ld demonstrates a durable and clinically relevant improvement in progression-free survival and overall response rate,” the authors concluded. “The addition of elotuzumab to Ld was associated with minimal added toxicity compared with Ld alone.”

Doss, D., Colson, K., Gleason, C., Richardson, P., & Lonial, S. (2016). Elotuzumab, in combination with lenalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (ELOQUENT-2): A 3-year safety update. Poster presented at the ONS 41st Annual Congress, San Antonio, TX, April 28–May 1, 2016.