EXPERT ANALYSIS FROM IMEDEX: LYMPHOMA & MYELOMA
NEW YORK (FRONTLINE MEDICAL NEWS) – Monoclonal antibodies may soon have more of a role in the front-line treatment setting for multiple myeloma and as part of precollection/transplant regimens–or “so-called in vivo purges,” according to Tomer M. Mark, MD, of the department of clinical medicine at the Cornell University, New York.
They could also be used both in the preclinical setting for smoldering multiple myeloma, and for maintenance following transplant, which makes sense given that they are, for the most part, not myelosuppressive and have “very tolerable toxicities,” he said.
Myeloma is “sort of catching up to lymphoma in terms of antibody use and development. … Approval trials are underway,” Dr. Mark said at Imedex: Lymphoma & Myeloma, an international congress on hematologic malignancies.
The successes of the phase III trials CASTOR and POLLUX in patients with relapsed and refractory multiple myeloma have paved the way for trials to examine daratumumab in first-line combination therapy.
In POLLUX, progression-free survival, time to progression, and overall response rate were superior with daratumumab in combination with lenalidomide/dexamethasone, as compared with lenalidomide/dexamethasone alone, in relapsed or refractory multiple myeloma patients. In CASTOR, daratumumab in combination with bortezomib and dexamethasone was superior to bortezomib and dexamethasone alone in a similar patient population. Of note, the effect was attenuated in those with multiple prior lines of treatment, which is, perhaps, an argument for moving monoclonal antibodies closer to the start of therapy, he said.
Daratumumab (Darzalex), which targets CD38, is currently indicated for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and an immunomodulatory agent.
Similarly, elotuzumab (Empliciti), an immunostimulatory monoclonal antibody targeting a cell-surface receptor with both direct activation of natural killer cells and the capacity to trigger antibody-dependent, cell-mediated cytotoxicity of myeloma cells, is indicated in combination with lenalidomide/dexamethasone in patients who have received one to three therapies. Elotuzumab was shown in one trial to be associated with progression-free survival of 68% at 1 and 41% at 2 years when used with lenalidomide/dexamethasone. Patients receiving elotuzumab had a relative reduction of 30% in the risk of disease progression or death as compared with the control group.
In an ongoing trial with initial results reported at the 2015 American Society of Hematology annual meeting, elotuzumab with bortezomib/dexamethasone was associated with a more modest improvement in median progression-free survival, which was 9.9 months with triple therapy and 6.8 months with bortezomib/dexamethasone alone.
Both drugs have shown activity as single agents. In a phase I study, elotuzumab was associated with disease stability in 26% of patients, Dr. Mark said. Daratumumab, used as monotherapy in a study of relapsed or relapsed/refractory multiple myeloma patients, was associated with good overall response and progression-free survival, and “quite amazing” overall survival of 65%.
Other monoclonal antibodies in development include isatuximab (anti-CD38), lorvotuzumab mertansine (anti-CD56), and indatuximab ravtansine (anti-CD128), Dr. Mark said.
Dr. Mark reported receiving research funding from Celgene and Amgen, serving on speakers bureaus for Celgene, Millennium, Amgen, and Bristol-Myers Squibb, and serving on an advisory committee for Celgene and Millennium.
