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Daratumumab safely added to combination regimens for multiple myeloma
SAN FRANCISCO — The monoclonal antibody daratumumab added to combination backbone regimens safely treated patients with multiple myeloma, according to study results presented at the ASH Annual Meeting and Exposition.
“Daratumumab belongs to a new class of drugs called anti-CD38 monoclonal antibodies,” Maria-Victoria Mateos, MD, PhD, of the University Hospital of Salamanca/IBSAL in Salamanca, Spain, said during a press briefing. “Daratumumab as a single agent has been found to be effective in relapsed and refractory myeloma patients, and according to these results, the main objective of this phase 1 trial has been to combine this monoclonal antibody with different backbone regimens commonly used for the management of multiple myeloma patients.”
Maria-Victoria Mateos
Mateos and colleagues conducted a four-arm study with six patients assigned to each arm. All patients received 16 mg/kg daratumumab (Genmab/Janssen Biotech) combined with their assigned backbone regimen.
Researchers assigned patients who were newly diagnosed with multiple myeloma irrespective of their transplant eligibility to receive bortezomib (Velcade, Millennium Pharmaceuticals) plus dexamethasone or that combination plus thalidomide (Thalomid, Celgene) for 18 3-week cycles.
Patients who were newly diagnosed but ineligible to undergo transplant received nine 6-week cycles of bortezomib, melphalan and prednisone.
The fourth arm consisted of patients who had relapsed on or who were refractory to at least two lines of therapy with two consecutive cycles of lenalidomide (Revlimid, Celgene) and bortezomib. These patients received 4-week cycles of pomalidomide (Pomalyst, Celgene) and dexamethasone until disease progression.
The median duration of daratumumab treatment was 44 days (range, 1-113).
One hundred percent of newly diagnosed patients in the first three treatment arms responded to treatment with a very good partial remission or a partial remission. Fifty percent of patients in the relapsed group responded, which included one patient who achieved a complete remission and two who achieved very good partial remissions.
Researchers noted the only toxicities associated with the addition of daratumumab to the backbone regimens were infusion-related reactions in four patients. Most infusion-related reactions were grade 1, occurred on the first day of treatment and resolved with treatment. There were two cases of rash and one case of bronchospasm.
Other adverse events were likely related to the backbone regimens, researchers said. The most common adverse event of any grade was hematologic toxicity, and the most common grade 1 and grade 2 adverse events were peripheral sensory neuropathy, headache, asthenia, pyrexia and constipation. There were three cases of grade 3 neutropenia and one case of grade 3 anemia in the first three treatment arms. Five patients experienced grade 3 or worse neutropenia and two patients experienced grade 3 anemia in the fourth treatment arm.
“We consider the addition of 16 mg/kg daratumumab to the various backbones [to be] well tolerated in all evaluable patients and it did not result in significant additional toxicity,” Mateos said. “Daratumumab also was associated with high rates of response in combination with the different backbones.”
For more information:
Moreau P. Abstract #176. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.
Disclosure: Researchers report honoraria and research funding from and board of director, employment or advisory/consulting roles with Celgene, Janssen, Merck, Millennium: The Takeda Oncology Company, Novartis, Onyx, Prothena, and Teva.
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