Elotuzumab Plus PVd Has Antitumor Activity in Heavily Pretreated R/R Myeloma

Elotuzumab Plus PVd in R/R Myeloma

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The addition of elotuzumab (Empliciti) to pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) demonstrated antitumor activity with an expected safety profile in patients with relapsed/refractory multiple myeloma who had received a median of 3 prior lines of therapy and were previously treated with lenalidomide (Revlimid) and a proteasome inhibitor (PI).1

Data from the phase 2 trial (NCT02718833), which were published in Blood Advances, showed that in patients from the overall population (n = 48), the objective response rate (ORR) with elotuzumab plus PVd was 56.3% (95% CI, 42.3%-69.3%). A higher response rate of 73.7% (95% CI, 51.2%-88.2%) was shown in patients who had received 1 prior line of therapy. Additionally, the ORR was 44.8% (95% CI, 28.4%-62.3%) in patients who had received 2 or more prior lines of therapy. The ORR among patients who were previously treated with anti-CD38 antibody therapy was 35.7% (95% CI, 16.3%-61.3%).

“The safety profile of elotuzumab/PVd showed adverse effects [AEs] as expected from the drugs used in the regimen, with neutropenia and infections being the more common high-grade AEs,” lead study author Andrew J. Yee, MD, and coauthors wrote in the publication.

Yee is the clinical director of the Center for Multiple Myeloma at Massachusetts General Hospital, as well as an assistant professor of medicine at Harvard Medical School, both in Boston.

Diving Into the Background, Study Design, and Baseline Patient Characteristics

In November 2018, the FDA approved elotuzumab plus pomalidomide and low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma after previously receiving 2 or more therapies, which included lenalidomide and a PI.2 The regulatory decision was based on data from the phase 2 ELOQUENT-3 trial (NCT02654132), which evaluated elotuzumab plus pomalidomide and dexamethasone in this patient population.

The present multicenter, prospective phase 2 study evaluating the quadruplet of elotuzumab plus PVd included patients with relapsed/refractory multiple myeloma who had received at least 1 prior line of treatment, which included at least 2 cycles of lenalidomide and 2 cycles of a PI in separate regimens or as a simultaneous regimen.1 All patients on the trial with relapsed/refractory disease must have had disease progression within 60 days following the completion of their last therapy. Those with adequate organ function and measurable disease were included on the study, along with those who had received prior pomalidomide or bortezomib therapy.

All patients were treated with intravenous (IV) elotuzumab at 10 mg/kg weekly during cycles 1 to 2, then 10 mg/kg on days 1 and 15 of cycles 3 to 8, and 20 mg/kg on day 1 of cycles 9 and onward in 28-day cycles. Oral pomalidomide was given at 4 mg on days 1 to 21. Subcutaneous bortezomib was given at 1.3 mg/m2 on days 1, 8, and 15 of cycles 1 to 8. In cycle 9 and beyond, subcutaneous bortezomib was administered on days 1 and 15.

The primary end point was ORR per the International Myeloma Working Group criteria; secondary end points were progression-free survival (PFS) and safety.

In the overall population, the median age was 64 years (range, 40-80), and 73% of patients were male. Of note, patients were White (83%), Asian (8.3%), Black (4.2%), or other (4.2%). The median number of prior lines of therapy was 3 (range, 1-9); patients had received 1 (40%), 2 (8.3%), 3 (16.7%), or 4 or more (35%) prior lines. Additionally, 6%, 12%, and 50% of patients had stage I, II, or III disease, respectively, per the International Staging System. Previous therapies included autologous stem cell transplantation (48%), an immunomodulatory drug (100%), lenalidomide (100%), and pomalidomide (33%). The most common PI patients had previously received was bortezomib (96%), and the most common CD28-directed monoclonal antibody patients had previously received was daratumumab (Darzalex; 25%). Most patients had standard-risk disease per fluorescence in situ hybridization (FISH; 44%), and 25% of patients had high-risk disease. Furthermore, deletion 17p, translocation 4;14, translocation 14;16, and 1q gain were present in 17%, 6%, 4%, and 29% of patients, respectively.

Sharing Additional Efficacy and Safety Data

At a median follow-up of 36.8 months, the median PFS was 10 months (95% CI, 7.75-20.1). The median PFS in patients who had received 1 prior line of therapy and were refractory to lenalidomide (n = 19) was 23.4 months (95% CI, 10-not reached [NR]). The median PFS was 7.75 months (95% CI, 6.54-13.1) in patients who were treated with 2 or more prior lines of therapy. Moreover, patients treated with a prior anti-CD38 antibody had a median PFS of 5.82 months (95% CI, 2.8-27.9), and those treated with this class of agent in their last line of therapy had a median PFS of 7.69 months (95% CI, 2.83-NR). Patients with high-risk disease per FISH had a median PFS of 8.89 months (95% CI, 6.54-NR). Of note, the median overall survival for all treated patients was 25.2 months (95% CI, 18.4-NR).

Regarding safety, the most common grade 3 or greater AEs included neutropenia (33%), infections of any type (33%), lung infection (27%), hypophosphatemia (19%), and thrombocytopenia (15%). Notably, 2 patients had febrile neutropenia. At the time of disease progression, 2 patients died, 1 each due to Escherichia coli bacteremia and pneumonia. There were no infusion-related reactions associated with elotuzumab; however, there were 3 grade 3 incidences of rash associated with pomalidomide.

Three patients discontinued treatment, 1 each because of stroke, pulmonary embolism leading to death, and infection. Additionally, most patients had dose reductions. Pomalidomide doses were reduced to 3 mg in 25 patients, 2 mg in 5 patients, and 1 mg in 2 patients. In a similar trend, bortezomib dosing was reduced to 1 mg/m2 in 14 patients and 0.7 mg/m2 in 4 patients. The dose of oral dexamethasone was reduced in 24 patients, and 7 patients required a reduced dose of IV dexamethasone.

“Given the rapidly changing treatment landscape, the place of elotuzumab is undergoing further examination,” the study authors concluded. “Overall, the findings from this phase 2 trial of elotuzumab/PVd support the use of this combination in this changing landscape.”

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. U.S. Food and Drug Administration approves Empliciti (elotuzumab) plus pomalidomide and dexamethasone, a new immunotherapy combination for certain patients with relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. November 6, 2018. Accessed May 27, 2025. https://news.bms.com/news/details/2018/US-Food-and-Drug-Administration-Approves-Empliciti-elotuzumab-Plus-Pomalidomide-and-Dexamethasone-a-New-Immunotherapy-Combination-for-Certain-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx