Published: Dec 8, 2014 | Updated: Dec 9, 2014
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- The novel monoclonal antibody daratumumab appeared to work well with a variety of backbone regimens in multiple myeloma.
- Note that serious adverse events primarily stemmed from the backbone regimens, but there was one case of "laboratory testing interference" related to daratumumab.
The novel monoclonal antibody daratumumab appeared to work well with a variety of backbone regimens in multiple myeloma, a small, early-phase study suggested.
Four different combinations were well tolerated without significant additional toxicity from the human anti-CD38 monoclonal antibody, Maria-Victoria Mateos, MD, PhD, of the University Hospital of Salamanca, Spain, and colleagues found.
Across the regimens in the 25-patient, open-label, phase I trial, the overall response rate was 100% in newly-diagnosed patients and 50% in those who had relapsed, the researchers reported here at the American Society of Hematology (ASH) meeting.
Daratumumab was associated with a 100% "very good" partial or complete response rate when combined with:
- Bortezomib (Velcade) and dexamethasone
- Bortezomib, melphalan (Alkeran), and prednisone
- Bortezomib, thalidomide (Thalomid), and dexamethasone
The fourth combination with daratumumab added to pomalidomide (Pomalyst) and dexamethasone -- which Mateos noted is used in relapsed and refractory patients -- had one complete response and two very good partial responses (90% or greater reduction in monoclonal protein biomarkers) but two minimal responses and one progression of disease among the six evaluable patients.
Median time to first response was rapid, consistent with what had previously been seen with the various backbone regimens, Mateos said, speaking at an ASH press conference in lieu of session presenter Philippe Moreau, MD, of the University Hospital of Nantes, France.
The drug had previously been tested as a single agent.
"I do think these anti-CD38 antibodies, these are the next blockbuster agents," said Thomas Martin III, MD, of the University of California San Francisco, who presented a phase Ib trial with another novel agent in the class, SAR650984, at the conference.
"These are the next agents that are really going to show some benefit to myeloma patients, and the next 5 years are going to be really fun moving them from the refractory setting to the less refractory setting to the front-line setting," he told reporters at the press briefing.
"Blockbuster is a big word, obviously," cautioned Brad Kahl, MD, press conference moderator and clinical research director for hematologic malignancies at the University of Wisconsin Carbone Cancer Center in Madison.
"Obviously it's very, very early, so probably too early to plant the victory flag in the ground," he told reporters. "Having said that, the early data is very promising. It totally justifies all the comments said earlier about bringing these drugs forward aggressively, moving them into the front line."
Mateos's multicenter study had five patients electively taken off the study medication (one in the bortezomib/dexamethasone backbone regimen group, four in the bortezomib/thalidomide/dexamethasone-based treatment group) for stem-cell transplant after the fourth cycle of treatment.
Three of the patients on the pomalidomide/dexamethasone backbone regimen dropped out of the study; one on physician discretion after the first daratumumab dose and two after disease progression.
Serious adverse events primarily stemmed from the backbone regimens, but there was one case of "laboratory testing interference" related to daratumumab.
Other hematologic and nonhematologic toxicity was consistent with what has previously been reported with the backbone regimens, Mateos said.
Daratumumab infusion-related reactions were mostly grade 1 or 2 and occurred during the first infusion.
Mateos acknowledged that the number of patients in her trial was "very small but we have demonstrated that the combination is feasible, and so the next step is to conduct phase III randomized trials with the different backbone regimens combined with daratumumab."
Several such trials will likely start next year, she said at the press conference.
The trial was sponsored by Janssen.
Mateos disclosed relevant relationships with Janssen.
Martin disclosed relationships with Sanofi and Novartis.
Kahl disclosed relationships with Celgene Corporation, Cell Therapeutics, Genentech, Gilead Sciences, Infinity Pharmaceuticals, Millennium: The Takeda Oncology Company, Seattle Genetics, Roche, AbbVie, Allos, and Pharmacyclics.
Primary source: American Society of Hematology
Source reference: Moreau P, et al "An open-label, multicenter, phase 1b study of daratumumab in combination with backbone regimens in patients with multiple myeloma"ASH 2014; Abstract 176.