Lazaros John Lekakis, MD, associate professor of clinical medicine, Sylvester Comprehensive Cancer Center, University of Miami, discusses ways of managing the toxicity of CAR T-cell therapy.

One of the biggest challenges with CAR T-cell therapy is the toxicity profile, as there are a number of unanswered questions, Lekakis says. For grade 3/4 neurotoxicity, high-dose steroids are typically given. Steroids may also be appropriate for patients with grade 2 neurotoxicity, says Lekakis. However, researchers don’t yet know the impact of corticosteroids on T cells.

One toxicity that researchers struggle with is a rare condition called cerebral edema, Lekakis notes. This is the most severe case of neurotoxicity a patient can develop. Cerebral edema occurs in 1% to 2% of patients treated with CAR T-cell therapy, but it is mostly fatal. Physicians currently manage this with corticosteroids in an attempt to induce hypocapnia, but it remains a major challenge.

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Lazaros John Lekakis, MD, associate professor of clinical medicine, Sylvester Comprehensive Cancer Center, University of Miami, discusses managing the toxicity of CAR T-cell therapy.

Dr. Lekakis on Managing the Toxicity of CAR T-Cell Therapy

Lazaros John Lekakis, MD, associate professor of clinical medicine, Sylvester Comprehensive Cancer Center, University of Miami, discusses real-world data with CAR T-cell therapy from the 2018 ASH Annual Meeting.

The real-world data for the use of axicabtagene ciloleucel (axi-cel; Yescarta) came as a surprise to some physicians, says Lekakis. A lot of people in the community thought the ZUMA-1 trial data would not be reproducible in practice as there were very strict exclusion criteria for the study. However, the real-world data with over 200 patients showed a complete response rate that was consistent with the data from the ZUMA-1 trial.

Moreover, it was not the only trial that demonstrated those results in a real-world setting, says Lekakis. Taken collectively, these data show that approximately 37% of patients had no evidence of disease at the time of data cutoff. These patients are most likely cured because very few relapses happen after a 6-month cutoff, adds Lekakis.

Lazaros John Lekakis, MD, associate professor of clinical medicine, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses real-world data with CAR T-cell therapy from the 2018 ASH Annual Meeting.

Dr. Lekakis on Real-World Data With CAR T-Cell Therapy in Lymphoma

Lazaros John Lekakis, MD, associate professor of clinical medicine, Sylvester Comprehensive Cancer Center, University of Miami, discusses current research with chimeric antigen receptor (CAR) T-cell therapy across hematologic malignancies.

Bispecific CAR T cells are an area of active investigation in B-cell malignancies, explains Lekakis. Currently, tisagenlecleucel (Kymriah) and axicabtagene-ciloleucel (Yescarta) are approved for patients with relapsed or refractory diffuse large B-cell lymphoma, both of which target CD19. Some of the dual targets under investigation include CD19 and CD22. Dual-targeted CAR T cells may be more effective, explains Lekakis as CAR T-cell evasion can occur with CD19 clones, he explains.

In multiple myeloma, several products are under investigation—–all of which target BCMA. Some companies are combining CAR T cells with PD-1/PD-L1 inhibitors to try to evade T-cell exhaustion, explains Lekakis. Combinations of CD19-specific CAR T cells and lenalidomide (Revlimid) and rituximab (Rituxan) are also under exploration, adds Lekakis.

Lazaros John Lekakis, MD

Articles

Dr. Lekakis on Managing the Toxicity of CAR T-Cell Therapy

Dr. Lekakis on Real-World Data With CAR T-Cell Therapy in Lymphoma

Dr. Lekakis on Current Research With CAR T-Cell Therapy