ASBMT always strives to be a leader in our field – and that includes tackling issues in an ever-changing landscape. That’s why ASBMT leadership is proud to announce the publication of our paper on consensus grading for IEC toxicities, “ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells.”
Published in this very journal, the paper is authored by some of the best minds from around the world. Its inception began after CAR-T cell therapy started becoming one of the most encouraging forms of therapy for hematological malignancies. In recent years, there have been several different CAR-T products approved in the U.S. and Europe, including immunotherapies that use cell- and bi-specific antibody-based approaches.
They were highly successful too: Two CAR T products, tisagenlecleucel and axicabtagene ciloleucel were approved in 2017 in the U.S. and in 2018 in Europe for the treatment of multiply relapsed or refractory B-cell acute lymphoblastic leukemia in patients up to age 25 and multiply relapsed or refractory large B-cell lymphoma in adults, respectively. Tisagenlecleucel was also approved in the U.S. and Europe in 2018 for multiply relapsed or refractory large B-cell lymphoma in adults.
And while these therapies have promising results, they are associated with unique toxicities of cytokine release syndrome (CRS) and neurological toxicity. Some of these toxicities were serious. The symptoms clinicians were seeing with a few therapies were similar to a study published in the New England Journal of Medicine in 2006, where six young, male volunteers were given a low dose of TGN1412, a superagonist monoclonal antibody to CD28. They all required critical care for the rapid onset of multiorgan failure, fever, hypotension, respiratory failure, and more.
ASBMT leaders saw that the assessment and grading of these toxicities greatly varied in clinical trials. This made it hard to figure out the effectiveness and the safety of the therapies. More importantly, it proved difficult for clinicians to develop strategies treat and manage the toxicities. There was also no benchmark to differentiate the effects of neurological toxicities on children or for hospitalized adult CAR-T patients, some of whom are bedridden for related co-morbidities.
ASBMT wanted to come together and create our own system, something that could create a more unified understanding and grading system for CRS. Experts from around the field of cellular transplantation met last summer to workshop definitions and grading for CRS and neurotoxicity. Some of the key goals included:
- Provide a uniform consensus grading system for CRS and neurotoxicity associated with effector cell therapies for use across clinical trials and in the post-approval clinical setting
- Create a system that is objective, easy to use and that accurately categorizes the severity of toxicities
In June 2018, 49 experts from all aspects of the field met. ASBMT, along with representatives from the Center for International Blood and Marrow Transplant Research (CIBMTR), the American Society of Hematology (ASH), and the National Cancer Institute (NCI), among many others, began proposing new definitions and grading for immune effector cell-associated CRS and neurotoxicity.
We’re incredibly proud of the teamwork and camaraderie of this group. This paper is an important step forward in understanding and regulating cellular therapies, allowing them to become more widespread. The more we learn about these therapies, the more lives we can potentially save in the future.
ASBMT leadership, along with the incredibly talented authors of this paper, hope you take the time to read it and access our findings for yourself.