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Elotuzumab-Based Regimen Demonstrates Efficacy in Relapsed/Refractory Multiple Myeloma
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A phase 2 study showed that elotuzumab combined with pomalidomide, bortezomib, and dexamethasone was safe and efficacious.
Elotuzumab (Empliciti; Bristol Myers Squibb) in combination with pomalidomide (Pomalyst; Bristol Myers Squibb Pharmaceutical Corporation), bortezomib (Velcade; Millennium/Takeda and Janssen Pharmaceutical Companies), and dexamethasone (PVd) was a safe, efficacious quadruple therapy for treatment of patients with relapsed/refractory multiple myeloma (RRMM). The favorable results were seen in the phase 2 OPTIMISMM study (NCT02718833).1
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MM is an incurable disease, and most patients eventually relapse following treatment and become increasingly refractory with each successive line of therapy. Despite the development of novel agents, including immunomodulatory drugs, proteasome inhibitors, or monoclonal antibodies (mAb), which have yielded substantial outcomes, dynamic approaches are needed to manage the disease. Combination therapies have become first-line care for a multitude of cancers, including MM. Double, triple, and emerging quadruple therapies are at the forefront of clinical research and treatment of a broad spectrum of cancers.2
Elotuzumab is a humanized immunoglobulin G1 immunostimulatory mAb that targets signaling lymphocyte activation molecule F7 (SLAMF7), which is highly expressed on the surface of natural killer (NK) cells and myeloma cells but not on the surface of other healthy tissues. According to findings from other clinical trials, elotuzumab improved overall response rates (ORR) and progression-free survival (PFS) in various combinations, including lenalidomide and dexamethasone (ELOQUENT-2; NCT01239797); bortezomib and dexamethasone; and pomalidomide and dexamethasone (ELOQUENT-3; NCT02654132).2-4
In the multicenter, phase 2 OPTIMISMM study, researchers evaluated the safety and efficacy of elotuzumab plus PVd (elo-PVd) in 48 patients with RRMM who had received a median of 3 prior lines of therapy (range, 1 to 9). They received the treatment in 28-day cycles. Elotuzumab was administered at 10 mg per kg intravenously (IV) weekly for the first 2 cycles. During cycles 3 to 8, it was given at the same dose on days 1 and 15. Starting in cycle 9, the dose was increased to 20 mg per kg IV on day 1 of each cycle. Pomalidomide was taken at 4 mg orally once daily on days 1 through 21 of each cycle. Bortezomib was administered subcutaneously at 1.3 mg per m² on days 1, 8, and 15 for the first 8 cycles. From cycle 9 onward, it was given only on days 1 and 15.2
Dexamethasone was used as a premedication when elotuzumab was given. Patients took 28 mg orally between 3 and 24 hours before the infusion, followed by an additional 8 mg dose 45 to 90 minutes before the infusion. On weeks without elotuzumab, dexamethasone was given as a 40 mg weekly dose, which could be split over 2 days if necessary.2
The primary end point of the study was ORR, with secondary end points of PFS and safety. The ORR was 56.3% (95% CI, 42.3-69.3) for the overall population; however, patients who received 1 prior line of therapy had higher responses (73.7%; 95% CI, 51.2-88.2) than those with 2 or more prior lines of therapy (44.8%; 95% CI, 28.4-62.3). The median PFS was 23.4 months (95% CI, 10 to not reached) for patients who had received 1 previous line of therapy (n = 19; all lenalidomide resistant; bortezomib, n = 18; carfilzomib [Kyprolis; Onyx Pharmaceuticals], n = 1), and 7.75 months (95% CI, 6.54-13.1) for patients who had received 2 or more prior lines of therapy.2
The most frequent grade 3 or higher adverse events included neutropenia (33%), infections of any kind (33%), lung infection (27%), hypophosphatemia (19%), and thrombocytopenia (15%).2
The findings suggest that elo-PVd may be a safe and efficacious quadruplet therapy for some patients with MM. Continued studies are needed to fully determine its place in the MM treatment paradigm.
