Dickran G. Kazandjian, MD, professor of medicine, Myeloma Program, Sylvester Comprehensive Cancer Center, discusses the potential utility of bispecific T-cell engagers (BiTEs) in relapsed/refractory multiple myeloma.

BiTEs are monoclonal antibodies that utilize two binding domains, says Kazandjian. The first binds cytotoxic T cells to CD3, Kazandjian says. The second acts as a bridge to bring the T cell closer to a target on the myeloma cell, such as BCMA, Kazandjian says. In turn, this binding elicits an anticancer immune response, says Kazandjian.

Preliminary findings from studies evaluating BiTEs demonstrated high response rates in patients with heavily pretreated relapsed/refractory multiple myeloma, Kazandjian says. Moreover, some patients derived complete responses and minimal residual disease negativity, Kazandjian explains. It is currently too early to determine whether these responses are durable, but these initial results are encouraging, concludes Kazandjian.

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Dickran G. Kazandjian, MD, discusses the potential utility of bispecific T-cell engagers in relapsed/refractory multiple myeloma.  



Dr. Kazandjian on the Potential Utility of BiTEs in Relapsed/Refractory Multiple Myeloma 

Dickran G. Kazandjian, MD, professor of medicine, Myeloma Program, Sylvester Comprehensive Cancer Center, discusses novel therapeutic targets in multiple myeloma.

Bispecific T-cell engagers and CAR T-cell therapies directed toward novel targets, such as GPRC5D, are emerging in multiple myeloma, says Kazandjian.

Additionally, SLAMF7 is emerging as a potential target for CAR T-cell therapy in multiple myeloma, Kazandjian says. The SLAMF7-targeted monoclonal antibody elotuzumab (Empliciti) was approved in 2018 by the FDA for use in combination with pomalidomide (Pomalyst) and dexamethasone in certain patients with relapsed/refractory multiple myeloma.

In addition to novel targets, CAR T-cell therapies with improved stimulatory and binding domains are emerging in this disease, Kazandjian explains. For example, the phase 1/2 EVOLVE study (NCT03430011) is evaluating a newer CAR T-cell product orvacabtagene autoleucel (JCARH125) in patients with relapsed/refractory multiple myeloma, Kazandjian says. This therapy appears to have a low affinity for binding soluble BCMA, which could improve the therapy’s ability to bind to cell-surface BCMA on myeloma cells, concludes Kazandjian.

Dickran G. Kazandjian, MD, discusses novel therapeutic targets in multiple myeloma.  



Dr. Kazandjian on Novel Therapeutic Targets in Multiple Myeloma 

Dickran G. Kazandjian, MD, professor of medicine, Myeloma Program, Sylvester Comprehensive Cancer Center, discusses the rationale to evaluate retreatment with BCMA-directed therapy in multiple myeloma.

Retreatment with BCMA-targeted therapies is a reasonable therapeutic strategy for patients with multiple myeloma and is being adopted in clinical practice, says Kazandjian. Utilizing different modalities of BCMA-directed therapies may offer patients valuable treatment options, Kazandjian says.

However, evaluating BCMA-directed therapy retreatment has been challenging in the setting of clinical trials because many studies exclude relevant patients, says Kazandjian. For example, a study evaluating a BCMA-directed antibody-drug conjugate may exclude patients who received prior BCMA-directed CAR T-cell therapy, Kazandjian explains. 

If initial efficacy and safety signals emerge suggesting retreatment is feasible, clinical trial inclusion criteria may become less conservative, Kazandjian says. A similar clinical scenario was observed with the CD38-targeted monoclonal antibodies daratumumab (Darzalex) and isatuximab-irfc (Sarclisa), concludes Kazandjian.

Dickran G. Kazandjian, MD, discusses the rationale to evaluate retreatment with BCMA-directed therapy in multiple myeloma.  



Dickran G. Kazandjian, MD

Articles

Dr. Kazandjian on the Potential Utility of BiTEs in Relapsed/Refractory Multiple Myeloma

Dr. Kazandjian on Novel Therapeutic Targets in Multiple Myeloma

Dr. Kazandjian on Evaluating Retreatment With BCMA-Directed Therapy in Multiple Myeloma