Suzanne Lentzsch, MD, PhD, Director of the Multiple Myeloma and Amyloidosis Program, Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, served as the study’s discussant. She called the 29% response rate in this heavily pretreated or refractory population “quite remarkable” and emphasized that a subset achieved stringent complete responses and very good partial responses.
“The drug is quite active in patients with heavily pretreated myeloma, including 95% who were double-refractory. What’s also important, and I have seen this in my own patients, is that responses were rapid and improved over time,” she commented.
Dr. Lentzsch compared the single-agent activity of daratumumab with that seen with other antibodies. In a phase Ib study of heavily pretreated patients, SAR650984 (10 mg/kg) produced responses in 33%, including 11% complete responses.1 In contrast, elotuzumab, as a single agent, produced no responses, but 26.5% achieved stable disease.2
Monoclonal Antibodies in Combination
When these monoclonal antibodies were combined with lenalidomide (Revlimid) and dexamethasone, however, response rates increased for all drugs. With daratumumab/lenalidomide/dexamethasone, the response rate was increased to 87%, with 50% ≥ very good partial responses, in a study presented at the 2014 ASH Annual Meeting and Exposition.3 “I think that’s remarkable, and responses increased and deepened over time,” she noted.
With SAR650984 plus lenalidomide/dexamethasone, responses increased to 63%,4 and with elotuzumab/lenalidomide/dexamethasone, 92% of patients responded.5
She concluded, “We see dramatic increases in response to monoclonal antibodies when these drugs are combined with immunomodulatory drugs, so I think, based on these data, monoclonal antibodies will be the backbone of myeloma treatments in the future,… and I think it’s time for an R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] in myeloma!” ■
Disclosure: Dr. Lentzsch is on the advisory board of Celgene, Bristol-Myers Squibb, and Janssen and has received a research grant from Celgene.
References
1. Martin TG, Hsu K, Strickland SA, et al: A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma. 2014 ASCO Annual Meeting. Abstract 8532.
2. Zonder JA, Mohrbacher AF, Singhal S, et al: A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 120:552-559, 2012.
3. Plesner T, Arkenau H-T, Lokhorst H, et al: Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. 2014 ASH Annual Meeting. Abstract 84.
4. Martin TG, Baz R, Benson DM, et al: A phase 1b dose escalation trial of SAR650984 (anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma. 2014 ASH Annual Meeting. Abstract 83.
5. Richardson PG, Jagannath S, Moreau P, et al: Final results for the 1703 phase 1b/2 study of elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. 2014 ASH Annual Meeting. Abstract 302.
