EBMT NEWSLETTER | September 2017 | Volume 58 - Issue 4

Important dates
Novartis announced on August 30, 2017 that the FDA has approved a CAR-T cell therapy, Kymriah™ (tisagenlecleucel, CTL019), for children and young adults with B-cell acute lymphoblastic leukemia (ALL) that is refractory or has relapsed at least twice. For more information, read the press release.

We interviewed Professor Arnon Nagler, EBMT Board Member, to get his explanations and views about this important milestone: 
Professor Arnon Nagler, hematologist at the Chaim Sheba Medical Center, Tel-Hashomer and Chair of the EBMT Acute Leukaemia Working Party.  

Can you explain what the treatment requires?

Arnon Nagler: First and above all the expertise and experience in treating hematological malignancies and stem cell transplantation and cellular therapy; second, GMP facility; third, the construct and vector to be transfected into the T cells; fourth, molecular and cellular lab; fifth, approval by National and International regulatory bodies (for example JACIE) for the lab in general and for the CAR-T cells in particular.

Why does this represent a major advance in treating patients with Acute Lymphoblastic Leukaemia (ALL)?

Arnon Nagler: ALL that do not respond to initial therapy (resistant) and or relapse following therapy is a devastating disease that cannot be cured by chemotherapy. Cellular therapy in the form of allogeneic transplantation used and is still the only establish curative therapy. However, first, achieving complete response (CR) or reducing tumor burden pre transplant significantly increase the chance of success and second, transplant is with substantial toxicity that is reduced if patient arrive to the transplant in CR or with low tumor burden. CAR T cells is a novel mode of cellular immunotherapy that can achieve this goal and bridge the patient to transplant. Other options are novel recently approved monoclonal antibodies.

Does the CAR T-cell therapy pose safety risk?

Arnon Nagler: Yes, there are safety issues with CAR-T cells: mainly cytokine release syndrome (CRS) and neurotoxicity that some believe is part of the CRS. Incidence correlates with the tumor mass, for example: number of blasts and the number of the CAR-T cells infused. The treatment is based on anti IL-6 antibodies.

What are some of the main challenges in immunotherapy?

Arnon Nagler: Challenges in immunotherapy are efficacy and safety. The anti-tumor effect needs to be specific, stable and last for long time to ensure cure. It needs to reach the tumor and be effective. It should raise antibodies or resistance from the body and it should be safe with minimal side effects and no early or late toxicity.

The FDA discussed mandating a patient registry that would track patients for up to 15 years. Is it the EBMT patient registry?

Arnon Nagler: The EBMT has been developing a dedicated registry for cellular products and clinical trials of cell and cell-based gene therapy. This EBMT registry will be used to evaluate patient outcomes and CTL019's long- and short-term safety.
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