The addition of elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) induction and maintenance therapy did not improve outcomes compared with RVd alone in patients with high-risk multiple myeloma, according to the results of the phase 2 SWOG-1211 trial published in Lancet Oncology.1
Despite the availability of immunomodulatory agents and proteasome inhibitors, high-risk multiple myeloma is a disease marked by poor prognoses. The aim of this trial was to evaluate a novel regimen that included a standard-of-care immunomodulatory agent plus a proteasome inhibitor with the anti-SLAMF7 antibody elotuzumab.
“To our knowledge, the SWOG-1211 is the first randomized trial for newly diagnosed high-risk multiple myeloma,” the study authors wrote.
The phase 2 SWOG-1211 trial (ClinicalTrials.gov identifier: NCT01668719) randomly assigned 100 patients with newly diagnosed, high-risk multiple myeloma to receive induction therapy consisting either of elotuzumab plus RVd or RVd alone, followed by dose-attenuated maintenance therapy. Patients who received elotuzumab as part of their induction continued it during their maintenance therapy. The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), overall survival (OS), and toxicity.
At baseline, the median age was 64 years and 40% of patients were female. The majority of patients were classified as high-risk due to a gain or amplification in 1q21 (47%), followed by a deletion in 17p (37%), t(14,16; 11%), t(14;20; 5%), and 17% had 2 or more high-risk features. Most patients had stage II disease by the International Staging and Revised International Staging Systems criteria, followed by stage III and stage I disease. Lactate dehydrogenase levels were greater than 190 U/L in 52% and 50% of patients in the elotuzumab arm and RVd arms, respectively.
The combination of elotuzumab with RVd did not improve ORR (83% vs 88% in the RVd group [2-sided P =.29]). There was also no improvement seen in evaluations of very good partial response or better (2-sided P = .52) and complete response or better (2-sided P =.19).
At a median follow-up of 53.0 months, the median PFS was found to be similar between groups, with a median of 31.47 months with elotuzumab plus RVd compared with 33.64 months with RVd alone (HR, 0.968; 80% CI, 0.697-1.344; P =.45).
There was also no difference in OS, with a median not yet reached in the elotuzumab arm and a median of 68 months in the RVd arm (HR, 1.279; 80% CI, 0.819-2.00; 2-sided P =.48).
The rate of grade 3 or higher adverse events (AEs) was similar between the groups. However, infections, sensory neuropathy, and motor neuropathy were seen more commonly with elotuzumab. There was 1 grade 5 event in the elotuzumab group that was associated with multi-organ failure, “for which study treatment was listed as possibly contributing by the investigator,” the investigators wrote.
“The addition of elotuzumab to RVd induction and maintenance did not improve patient outcomes,” the study authors concluded. They added, however, that the results do “support the role for maintenance therapy with a continuous proteasome inhibitor and immunomodulatory drug combination for patients with high-risk multiple myeloma.”
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Usmani SZ, Hoering A, Ailawadhi S, et al; SWOG1211 Trial Investigators. Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): primary analysis of a randomised, phase 2 trial. Lancet Haematol. Published online December 22, 2020. doi:10.1016/S2352-3026(20)30354-9