Richard T. Maziarz, MD, professor of medicine at Oregon Health & Science University, Knight Cancer Institute, discusses unanswered questions with CAR T-cell therapy in diffuse large B-cell lymphoma (DLBCL).

Traditionally in DLBCL, physicians expected 15% to 20% of patients to be alive at the 2-year mark. Now, with the emergence of CAR T-cell therapy, researchers expect approximately 40% of patients to be alive at the 2-year mark. This is encouraging because a survival of at least 2 years indicates long-term survival, Maziarz says. However, that still leaves 60% of patients who need effective therapy. Therefore, a better understanding of what drives resistance is crucial.

Moreover, CAR T-cell therapy is associated with unique toxicities, and researchers need to make the treatment safer so more patients can receive it. For example, a proliferation event can occur as a result of cells growing fast.

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Richard T. Maziarz, MD, professor of medicine at Oregon Health & Science University, Knight Cancer Institute, discusses unanswered questions with CAR T-cell therapy in diffuse large B-cell lymphoma.

Dr. Maziarz on Unanswered Questions With CAR T-Cell Therapy in DLBCL

Richard T. Maziarz, MD, professor of medicine at Oregon Health & Science University, Knight Cancer Institute, discusses sustained responses with tisagenlecleucel (Kymriah) in the treatment of patients with diffuse large B-cell lymphoma (DLBCL).

The community was probably surprised at first that the chimeric antigen receptor (CAR) T-cell product proved effective in humans—not just mouse models, says Maziarz. In the JULIET trial, which had updated data presented at the 2018 ASH Annual Meeting, investigators reported sustained responses with tisagenlecleucel in this patient population, beyond the short-term. This is especially important to note due to the skepticism that often comes with early data from clinical trials, where a drug might induce a short-term response in patients due to several factors, such as selection. Data showing long-term durable responses with the agent confirm its utility.

At a median follow-up of 19 months, over 40% of the patients were reported to be in sustained remission and 54% of the patients have a complete or partial remission. Maziarz notes that the patients in partial remission can still go into complete remission because the CAR T cells continue to work over time and remain in the body indefinitely. The natural history of DLBCL has changed, said Maziarz; patients who have historically had a very poor prognosis now have a chance of extending survival.

Richard T. Maziarz, MD, professor of medicine at Oregon Health & Science University, Knight Cancer Institute, discusses sustained responses with tisagenlecleucel in the treatment of patients with diffuse large B-cell lymphoma.

Dr. Maziarz on Sustained Responses With Tisagenlecleucel in DLBCL

Richard T. Maziarz, MD, professor of medicine at Oregon Health & Science University, Knight Cancer Institute, discusses the promise of tisagenlecleucel (Kymriah) in the treatment of patients with diffuse large B-cell lymphoma (DLBCL).

The JULIET trial, which was presented at the 2018 ASH Annual Meeting, assessed the safety and efficacy of the CD19-directed chimeric antigen receptor T-cell product tisagenlecleucel in patients with relapsed/refractory DLBCL. In these patients, Maziarz says, their own immune cells have allowed the cancer to evade them and grow. With this therapy, investigators take the T cells out of the patients’ bodies and genetically alter them, and in doing so, these cells have a new receptor.

The beauty of this therapy, Maziarz says, is that immune cells live in the body for life. The mechanism of tisagenlecleucel alters the original receptor of the T cell—which may have been irrelevant to fighting the cancer&mdash;and directs it toward the disease.

In the study, overall response rate was 54% at a median follow-up of 19 months. There was a complete remission rate of 40%, with the rest of the responders achieving a partial response.

Richard T. Maziarz, MD, professor of medicine at Oregon Health & Science University, Knight Cancer Institute, discusses the promise of tisagenlecleucel in the treatment of patients with diffuse large B-cell lymphoma.

Richard T. Maziarz, MD

Articles

Dr. Maziarz on Unanswered Questions With CAR T-Cell Therapy in DLBCL

Dr. Maziarz on Sustained Responses With Tisagenlecleucel in DLBCL

Dr. Maziarz Discusses Promise of Tisagenlecleucel in DLBCL