Expert Discusses the Evolving Field of Multiple Myeloma

The treatment field of multiple myeloma is drastically changing, thanks to advances in antibodies, checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy.

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

Recently reported phase 2 data showed that combining Empliciti (elotuzumab) with Revlimid and dexamethasone induced a greater than 80 percent 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 percent in patients with relapsed/refractory multiple myeloma, according to interim findings of a phase 1 dose-escalation study (NCT02658929).

Could you provide an overview of immunotherapy in myeloma?

Could you expand on those combinations and their efficacy?

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

Eric Smith, M.D., Ph.D., 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 CURE to share his thoughts on the rapidly evolving treatment paradigm in multiple myeloma.I highlighted the combination therapy approach of antibodies targeting both the myeloma cells as well as checkpoint blockades with immunomodulatory drugs, such as Revlimid. I additionally focused on cellular therapy, such as donor transplants and CAR T-cell therapy.It is quite remarkable that monotherapy with either Empliciti or daratumumab is lacking efficacy, especially with Empliciti; however, in combination with Revlimid 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?

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 Rituxan (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.