Eric Smith, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses chimeric antigen receptor (CAR) T cell persistence in patients with multiple myeloma.

Smith says that a way to advance CAR T-cell therapy for patients with myeloma is with novel CAR T-cell vectors that enhance the depth and persistence of responses for patients. In myeloma, multiple studies with CD19 and BCMA CAR T cells have shown that the expansion and persistence of the gene-modified T cells correlate with deeper and more durable responses, he adds.

The reason that Smith says persistence is important is because a proportion of patients with myeloma are relapsing after CAR T-cell therapy. One reason for this relapse is that the target antigen gets downregulated or is not expressed in a small population of cells, and those cells end up growing out. For that reason, Smith says that investigators are looking at dual targeting.

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Dr. Smith Discusses CAR T Cell Persistence in Myeloma

Eric Smith, MD, PhD, medical oncologist, Memorial Sloan Kettering (MSK) Cancer Center, discusses novel chimeric antigen receptor (CAR) T-cell therapies in development for the treatment of patients with multiple myeloma.

Smith says that he spends most of his time in the laboratory, where he makes novel CAR T-cell designs that are aimed at increasing persistence. In myeloma, the CAR T-cell therapy with the most data is bb2121, which has been studied in the relapsed population in US-based clinical trials.

Another novel therapy is JCARH125, which is progressing in clinical trials now, although the results have yet to be reported. JCARH125 is a human-derived CAR T-cell therapy, which may limit the patient's immune response against the CAR T cell, Smith explains.

Other things that are being looked at for the next generation of CAR T-cell therapies include targeting more than 1 target with the same CAR vector. At MSK, Smith and his colleagues have created “armored CAR T cells,” which are modified to not only encode for the CAR, but also for a second gene that encodes a protein. This gives the T cells a further advantage to eradicate the myeloma in the immunosuppressive microenvironment, Smith says.

Eric Smith, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses novel chimeric antigen receptor (CAR) T-cell therapies in development for the treatment of patients with multiple myeloma.

Dr. Smith Discusses Novel CAR T-Cell Therapies for Myeloma

Eric Smith, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses CD19 (19-28Z) chimeric antigen receptor (CAR) T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL).

In a study of adult patients with relapsed/refractory B-ALL, investigators aimed to identify patients who would benefit from 19-28z CAR T-cell therapy, measured by durable long-term survival and reduced toxicities.

Results showed that the complete remission rate was 85% in this typically poor-prognosis setting.

Eric Smith, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses CD19 (19-28Z) CAR T-cell therapy in B-cell acute lymphoblastic leukemia.

Dr. Smith Discusses CD19 CAR T-Cell Therapy in B-ALL

Eric Smith, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses chimeric androgen receptor (CAR) T-cell therapy in multiple myeloma.

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

Smith says that next steps are going to include using a fully human CAR to minimize the potential immune responses against CAR.

Dr. Smith Discusses CAR T Cells in Multiple Myeloma

Eric Smith, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the potential of immunotherapy in the treatment landscape of multiple myeloma.

Smith sees a huge role for immunotherapy in the field. Although the disease is still considered incurable, immunotherapy is a hopeful way to shift that paradigm and get durable responses—or even cures&mdash;in patients. Additionally, he says, monoclonal antibodies such as upfront daratumumab (Darzalex) could have the same impact as rituximab (Rituxan) has had in non-Hodgkin lymphoma. There is also room for checkpoint blockades and chimeric antigen receptor (CAR) T-cell therapy in frontline and later-lines of therapy. CAR T-cell therapy could replace high-dose melphalan (Alkeran) in stem cell rescue in the future, he adds.

It is important for community oncologists to know that there are many therapeutic options available, especially for relapsed/refractory patients, but they should also consider referring patients to clinical trials that are exploring checkpoint blockades or cellular therapies.

Eric Smith, MD, PhD

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Dr. Smith Discusses CAR T Cell Persistence in Myeloma

Dr. Smith Discusses Novel CAR T-Cell Therapies for Myeloma

Dr. Smith Discusses CD19 CAR T-Cell Therapy in B-ALL

Dr. Smith Discusses CAR T Cells in Multiple Myeloma

Dr. Smith on Immunotherapy Potential in Multiple Myeloma