In patients with newly diagnosed multiple myeloma, elotuzumab plus bortezomib, lenalidomide, and dexamethasone (Elo-RVD) was associated with significant toxicity and infections, according to preliminary results from an open-label, single arm, phase IIa study (abstract 8002) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2-6 in Chicago.
“The combination of elotuzumab plus RVD was associated with a level of overall response similar to prior studies of RVD in newly diagnosed multiple myeloma,” reported lead study author Jacob Laubach, MD, of the Dana-Farber Cancer Institute in Boston. “A higher than expected number of patients (6/40, 15%) discontinued therapy within the first 4 cycles of treatment due to adverse events. Infection occurred in 50% of patients overall, including one grade 5 sepsis, one grade 4 sepsis, and four patients with grade 3 or higher lung infection.”
Despite the high rate of adverse events, the high rate of overall response among patients receiving 4 or more cycles of therapy was “promising,” Laubach said.
He said that dose and schedule modifications might improve toxicity rates.
Elotuzumab is a humanized IgG1 monoclonal antibody that is approved by the US Food and Drug Administration for use in combination with lenalidomide and dexamethasone as a treatment for relapsed and refractory multiple myeloma. The study authors evaluated the efficacy and safety of 4 cycles of elotuzumab plus lenalidomide, subcutaneous bortezomib, and dexamethasone in newly diagnosed, transplant-eligible patients with multiple myeloma.
Newly diagnosed patients underwent induction therapy with 4 cycles of Elo-RVD and stem cell mobilization, and then either immediate autologous stem cell transplantation (ASCT) or 4 cycles of Elo-RVD. Subsequent maintenance therapy involved 28-day cycles of Elo-RVD for high-risk patients (those with ISS stage III and/or high-risk cytogenetics) or elotuzumab, lenalidomide, and dexamethasone for standard-risk patients (ISS stage I or II without high-risk cytogenetics), until disease progression.
After 4 cycles, 33 of 40 patients experienced partial or complete responses, for an overall response rate of 82%. Median time to first response was 25 days, and the median duration of response had not been reached at the time of analysis. Half (50%) of the patients who did not undergo ASCT and 90% of those who underwent ASCT remained on treatment at the time of analysis.
The most common adverse events (all grades) included fatigue (60% of participants), neuropathy (55%), musculoskeletal and joint pain (55%), infection (50%), back or neck pain (48%), and diarrhea (45%). Grade 3 or higher hematologic events included thrombocytopenia (10% of patients), anemia (5%), febrile neutropenia (5%), lymphopenia (2%), and neutropenia (2%). The most common grade 3 or higher non-hematologic adverse events included hypophosphatemia (12%), fatigue (10%), lung infection (10%), hypertension (10%), increased ALT (5%), and syncope (5%).
Two study participants died. One patient died of sepsis and respiratory failure after treatment cycle 2. Another patient died more than 30 days after discontinuing treatment following hospitalization after cycle 1 for febrile neutropenia and sepsis-related hypotension, and subsequent kidney failure. The research team also recorded grade four cases of thrombocytopenia (5% of patients), hyperglycemia (2%), cardiac arrest (2%), and respiratory failure (2%). Five other study participants discontinued treatment following the emergence of toxicities, including peripheral neuropathy, mood disturbance, hyperglycemia, orthostatic hypotension, demyelinating polyneuropathy, and lung infection.
Dr. Laubach disclosed consulting and research funding from Novartis, Takeda, Janssen, Celgene, and Bristol-Myers Squibb.