CAR-Modified T Cell Therapy in ALL

Panelists: Dan Douer, MD, MSK; Richard M. Harris, MD, Cedars Sinai; Jeffrey Lancet, MD, Moffitt; Mark R. Litzow, MD, Mayo Clinic; Leonard S. Sender

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Chimeric antigen receptor (CAR) T cell therapies are engineered through the genetic modification of an individual’s T cells to express a synthetic receptor that recognizes a particular antigen or protein, explains Dan Douer, MD. The process of transforming the T cells in the laboratory can take 4 to 5 weeks, which may be too long of a delay in the treatment of acute lymphoblastic leukemia, Douer suggests.

Severe cytokine release syndrome is the main adverse event with the CAR T cell therapies, Douer notes. This side effect occurs when a mixture of cytokines are released after activated T cells attack leukemic cells. Clinical presentation ranges from fever to septic shock. Other toxicities include neurologic side effects, such as seizures and altered mental status, notes Douer.

Similarities exist between CAR T-cell therapies and blinatumomab, explains Douer. In general, both therapies target CD19 and recruit the immune system to attack the cancer. Whether these two methods of treatment can be sequenced or combined remains unanswered, notes Mark R. Litzow, MD.

PD-1 and PD-L1 targeted monoclonal antibodies represent another potential immunotherapy strategy on the horizon for patients with B cell malignancies, believes Raoul Tibes, MD. These immune checkpoint inhibitors are approved in melanoma and lung cancer and are currently being evaluated in lymphoma, myelodysplastic syndromes, and other malignancies.
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