Paul G. Richardson, MD

Study discussant Paul G. Richardson, MD, the RJ Corman Professor of Medicine at Harvard Medical School and the Jerome Lipper Multiple Myeloma Chair at Dana-Farber Cancer Institute, Boston, commented, “The evolving role of monoclonal antibodies in multiple myeloma has been worth the wait. You can see from the CASTOR study that we are really transforming outcomes with the advent of these molecules.”

“CASTOR’s progression-free survival is dramatic, and, as Dr. Palumbo said, unprecedented. It’s also important to recognize the high rate of complete responses and minimal residual disease negativity. Particularly impressive is the effect in patients with only one prior line of treatment,” he commented.

Numerous Mechanisms of Action

Monoclonal antibody–based targeting of myeloma works through numerous mechanisms, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and apoptosis/growth arrest via targeting of signaling pathways. “What’s so striking from CASTOR is that the direct antitumor effect appears to be so important,” he observed. “The mechanism driving [efficacy] suggests the apoptotic pathway is important.”

The benefit of the DVd (daratumumab, bortezomib, dexamethasone) triplet notwithstanding, Dr. ­Richardson also noted that “the signal is even more pronounced” when daratumumab is combined with lenalidomide/dexamethasone.

Additional Studies With Daratumumab

In a study from the 2015 ASH Annual Meeting, Plesner et al reported that 81% of patients responded to daratumumab plus lenalidomide/dexamethasone and 63% of patients achieved ≥ a very good partial response.¹ Also reported at ASH, the combination of daratumumab and pomalidomide (Pomalyst)/dexamethasone produced a response rate of 71% and ≥ a very good partial response rate of 43%.²

At the European Hematology Association Annual Meeting, results will be reported for the POLLUX study of daratumumab plus lenalidomide/dexamethasone. They showed a median progression-free survival that was not reached for daratumumab, lenalidomide (Revlimid), and dexamethasone, compared with 18.4 months for lenalidomide and dexamethasone, yielding a hazard ratio of 0.37 (P < .0001).³

“In the relapse setting, this is quite remarkable,” Dr. Richardson noted. “Truly, the advent of the monoclonal antibody platform has resulted in unprecedented hazard ratios and dramatically improved patient outcome.” ■

Disclosure: The study was funded by Janssen Research and Development.

References

1. Plesner T, Hendrik-Tobias A, Gimsing P, et al: Daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: Updated results of a phase 1/2 study (GEN503). 2015 ASH Annual Meeting. Abstract 507. Presented December 7, 2015.

2. Chari A, Lonial S, Suvannasankha A, et al: Open-label, multicenter, phase 1b study of daratumumab in combination with pomalidomide and dexamethasone in patients with at least 2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma. 2015 ASH Annual Meeting. Abstract 508. Presented December 7, 2015.

3. Dimopoulos M, Oriol A, Nahi H, et al: An open-label, randomized phase 3 study of daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: POLLUX. 2016 European Hematology Association Annual Meeting. Abstract LBA2238. Presented June 10, 2016.