Expert Highlights Immunotherapy Advances in Myeloma

Eric Smith, MD, PhD

Advances with antibodies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T-cell therapies are rapidly transforming the treatment landscape in multiple myeloma.

In November 2016, the FDA approved daratumumab in combination with lenalidomide (Revlimid) and dexamethasone or bortezomib (Velcade) and dexamethasone for patients with relapsed multiple myeloma following at least 1 prior therapy.

Recently reported phase II data showed that combining elotuzumab (Empliciti) with lenalidomide (Revlimid) and dexamethasone induced a greater than 80% response rate in patients with high-risk smoldering multiple myeloma.

And the investigational anti—B-cell maturation antigen (BCMA) CAR T-cell therapy bb2121 had an objective response rate of 78% in patients with relapsed/refractory multiple myeloma, according to interim findings of a phase I dose-escalation study (NCT02658929).

OncLive: Could you provide an overview of your talk on immunotherapy in myeloma?

Could you expand on those combinations and their efficacy?

Regarding the CAR T-cell, what are the next steps?

Eric Smith, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discussed several of these treatments at the 2016 Chemotherapy Foundation Symposium. During the meeting, Smith sat down with OncLive to share his thoughts on the rapidly evolving treatment paradigm in multiple myeloma.Smith: I highlighted the combination therapy approach of antibodies targeting both the myeloma cells as well as checkpoint blockades with immunomodulatory drugs, such as lenalidomide. I additionally focused on cellular therapy, such as donor transplants and CAR T-cell therapy.It is quite remarkable that monotherapy with either elotuzumab or daratumumab is lacking efficacy, especially with elotuzumab; however, in combination with lenalidomide and dexamethasone we've seen some interesting results. Advances in CAR T-cells for multiple myeloma are very exciting, the target right now seems to be BCMA. There are some initial studies coming out of the National Cancer Institute and the University of Pennsylvania that show remarkable efficacy in at least a subset of patients being treated at high doses.

What role do you foresee immunotherapy having in this disease?

What do you hope community oncologists take away from your presentation?

The next steps are going to include using a fully human CAR to minimize the potential immune responses against chimeric androgen receptors, which is shown to be clinically relevant in some lymphoma patients. Either using CAR T-cells in combination with drugs such as checkpoint blockade or using CAR T-cells that express more than one gene, both B-chimeric antigen receptors and then another gene to give them an advantage in the immune suppressive tumor microenvironment.I see a huge role for immunotherapy, even though myeloma is still considered incurable. Immunotherapy is a way to hopefully shift that paradigm and get durable responses—or even cures. I see antibodies such as daratumumab targeting the myeloma cells and upfront, will hopefully be myeloma's rituximab. And certainly, there is a lot of room for checkpoint blockades and for CAR T-cell therapy in the later stages of disease also moving upfront. CAR T-cell therapy could replace high dose melphalan in stem cell rescue in the future. I hope that they learned that there are a lot of options out there, especially for relapsed and refractory myeloma, and that they will carefully consider referral for clinical trials, either with checkpoint blockades or with cellular therapies.

References

1. Ghobrial IM, Badros AZ, Vredenburgh JJ, et al. Phase II trial of combination of elotuzumab, lenalidomide, and dexamethasone in high-risk smoldering multiple myeloma. Presented at: American Society of Hematology 58th Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract 976.
2. Badros AZ, Hyjek E, Ma N, et al. Pembrolizumab in Combination with Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM). Presented at: 58th ASH Annual Meeting and Exposition; San Diego, California; December 3-6, 2016. Abstract 490.