Elotuzumab Plus PVd Displays Efficacy in Relapsed/Refractory Multiple Myeloma

Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone was well tolerated in patients with relapsed/refractory multiple myeloma.

Elotuzumab (Empliciti) in addition to pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (elo-PVd) exhibited efficacy and tolerability in patients with relapsed/refractory multiple myeloma who received at least 1 prior line of therapy, according to findings from a prospective phase 2 trial (NCT02718833) published in Blood Advances.¹

Efficacy data revealed that among 48 patients treated with elo-PVd, the overall response rate (ORR) was 56.3% (95% CI, 42.3%-69.3%), while for those treated with only 1 prior line of therapy, it was 73.7% (95% CI, 51.2%-88.2%), and those with 2 or more lines of therapy had an ORR of 44.8% (95% CI, 28.4%-62.3%). Additionally, among patients who received prior anti-CD38 antibody therapy, the ORR was 35.7% (95% CI, 16.3%-61.3%).

In the overall population, the median progression-free survival (PFS) was 10.0 months (95% CI, 7.75-20.1) at a median follow up of 36.8 months; among those who received only 1 prior line of therapy, the median PFS was 23.4 months (95% CI, 10.0-not reached [NR]), and those with 2 or more lines of therapy it was 7.75 months (95% CI, 6.54-13.1). Furthermore, the median PFS was 5.82 months (95% CI, 2.8-27.9) among patients who received prior anti-CD38 antibody therapy, and was 7.69 months (95% CI, 2.83-NR) if it was the last line of therapy. For those with high-risk fluorescence in situ hybridization, the median PFS was 8.89 months (95% CI, 6.54-NR).

The median OS for the entire population was 25.2 months (95% CI, 18.4-NR).

“In this phase 2 trial of [patients with] relapsed/refractory [disease] with a median of 3 prior lines of therapy and prior treatment with lenalidomide and a proteasome inhibitor, we found that the combination of elo-PVd yielded an ORR of 56.3% and a median PFS of 10.0 months,” Andrew J. Yee, MD, assistant professor of medicine at Harvard Medical School and clinical director of the Center for Multiple Myeloma at Massachusetts General Hospital, wrote in the publication with study coinvestigators.¹ “These response rates are notable given the extensive prior treatment history: [33% were previously exposed to pomalidomide, 29% to carfilzomib, and 29% to an anti-CD38 antibody]; 13% of patients were penta-drug exposed (ie, exposure to these 3 agents along with lenalidomide and bortezomib). The safety profile of elo-PVd showed adverse effects as expected from the drugs used in the regimen...”

The trial enrolled patients with relapsed/refractory multiple myeloma having received at least 2 cycles of lenalidomide and 2 cycles of a proteasome inhibitor to receive elo-PVd. Patients treated with prior pomalidomide or bortezomib therapy were permitted for enrollment; prior elotuzumab therapy was not permitted.

Those treated received 10 mg/kg of intravenous elotuzumab once weekly for one to two 28-day cycles; biweekly for cycles 3 to 9, and then 20 mg/kg on day 1 of each cycle thereafter. Patients additionally received 4 mg of oral pomalidomide on days 1 to 21; as well as 1.3 mg/m² of subcutaneous bortezomib on days 1, 8, and 15 for cycles 1 to 8; and days 1 and 15 as an injection for each cycle thereafter. Dexamethasone was received at 28 mg orally between 3 to 24 hours before elotuzumab infusion and then 8 mg 45 to 90 minutes before infusion; on weeks without elotuzumab, 40 mg of dexamethasone was given weekly.

Patients on trial had a median age of 64 years (range, 40-80), 73% were male, and 83% were White. The median number of prior lines of therapy was 3 (range, 1-9); 40% of patients had only 1 prior line of therapy and 35% had 4 or more lines of therapy. A total of 50% of patients had International Staging System (ISS) stage III disease, and 44% were classified standard risk by fluorescence in situ hybridization (FISH).

The co-primary end points of the study were ORR and treatment-related adverse effects (TRAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria.² The secondary end point was PFS.

The most common hematologic AEs included neutrophil count decrease (any-grade: 60%; grade 3 or higher: 33%), anemia (60%, 10%), white blood cell decrease (54%, 19%), and platelet count decrease (48%, 15%). The most common non-hematologic AEs included fatigue (75%, 2%), infections (75%, 33%), upper respiratory infection (60%, 4%), hyperglycemia (56%, 4%), diarrhea (56%, 2%), and musculoskeletal pain (54%, 4%.

A total of 2 deaths were attributable to infection at the time of disease progression, due to Escherichia coli bacteremia and pneumonia. No infusion-related reactions were observed with elotuzumab. Three grade 3 instances of rash attributable to rash occurred but were resolved with supportive measures. Additionally, treatment-related discontinuations occurred in 3 patients and included stroke, pulmonary embolism leading to death, and infection.

References

1. Yee AJ, Laubach JP, Campagnaro EL, et al. Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma. Blood Adv. 2025;9(5):1163-1170. doi:10.1182/bloodadvances.2024014717
2. A study of elotuzumab with pomalidomide, bortezomib, and dexamethasone in relapsed multiple myeloma. ClinicalTrials.gov. Updated April 16, 2024. Accessed March 11, 2025. https://tinyurl.com/mptp5sua