Real-World Data Enhance Optimal Use of Cellular Therapies

Robert L. Ferris, MD, PhD

Lineberger Distinguished

Professor
Executive Director
UNC Lineberger Comprehensive Cancer Center and Chief of Oncology Services

UNC Health System

Chapel Hill, NC

Therapeutic opportunities for hematologic malignancies have rapidly advanced over the past 8 years. In particular, the advent of cellular therapies, such as chimeric antigen receptor (CAR) T-cell therapy, has revolutionized the field, where chemotherapy and targeted therapeutic drugs had been the primary approach. Even as CAR T-cell therapy is approved across a number of hemato- logic malignancies, the emergence of protein-engineered bispecific antibody therapy in diffuse large B-cell lymphoma and follicular lymphoma can now reach its full potential.

Together, these cellular treatments present unique logistical and accessibility challenges, and they demand safety and toxicity vigilance. Both require specialized health care centers with experience in toxicities and case management. The short- and long-term toxicities primarily include cytokine release syndrome driven by activated lymphocyte populations, as well as depletion of B cells and associated antibody titers, and the toxicities can lead to infectious complications due to cytopenia.

Direct head-to-head study is warranted in terms of efficacy and sequencing. Further, real-world data may expand the treatments to groups not usually enrolled in prospective, randomized, registrational phase 3 trials, such as Black and Hispanic individuals, or those in rural or underserved socioeconomic areas. During the 42nd Annual CFS, Jennifer Amengual, MD, presented real-world data suggesting that Black patients appeared to have inferior progression-free survival rates and Hispanic groups appeared to have slightly worse overall survival (Page 35). Furthermore, the use of CAR T-cell therapies in older patients is being explored in the clinic despite fewer of these individuals in clinical trials due to factors such as performance status.

In all, it is an exciting time in the hematologic malignancy and aggressive refractory lymphoma space. CAR T cells and bispecific antibodies are both effective and manageable therapies that take advantage of gene and protein engineering technologies. In the real world, patients in every racial and socioeconomic or ethnic group may appear more ill and may not have the ultimate outcomes. These are important data to consider outside clinical trials, particularly for expensive therapies that need to be delivered for optimal benefit in as many populations as possible.