ADC and CAR T-Cell Therapy Put DLBCL in the Spotlight at ASH Conference

According to John M. Burke, MD, clinical trial results presented at the ASH Annual Meeting may change the management of diffuse large B-cell lymphoma.

As the new co-editor of Targeted Therapies in Oncology™ (TTO), I am delighted and honored to work alongside Dr. Robert Ferris and the entire TTO team. My clinical practice focuses on hematological malignancies, and what better problem for me to start than one focused on the 2021 Annual Meeting of the American Society of Hematology (ASH). In recent years, at the ASH conference, diffuse large B-cell lymphoma (DLBCL) has taken precedence over other hematological malignancies.

This year at ASH was different. Two major developments have the potential to revolutionize the management of DLBCL in more than 2 decades. The first development was the POLARIX trial (NCT03274492). In the trial, patients with previously untreated DLBCL were randomly assigned to chemotherapy R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or anti-CD79b antibody conjugate polatuzumab vedotin (Polivy) plus R- CHP (pola-R-CHP). Pola-R-CHP improved progression-free survival and reduced the need for additional antilymphoma therapy; however, the complete response rate and overall survival were not affected.

The second major development was the study of chimeric antigen receptor (CAR) T cell therapy in the management of first relapse of DLBCL. Three studies compared CAR T-cell therapies with conventional high-dose chemotherapy and autologous stem cell transplantation in patients whose DLBCL had relapsed within 12 months of their initial treatment. In the ZUMA-7 trial (NCT03391466), axicabtagene ciloleucel (axi-cel; Yescarta) improved event-free survival (EFS) and response rates. In the TRANSFORM trial (NCT03575351), lisocabbagen maraleucel (liso-cel; Breyanzi) improved EFS, progression-free survival and complete response rate. Paradoxically, however, in the BELINDA trial (NCT03570892), tisagenlecleucel (tisa-cel; Kymriah) did not improve EFS or response rate compared to standard therapy.

Taken together, these findings have the potential to change the management of DLBCL. Whether the standard of first-line R-CHOP followed by high-dose chemotherapy and autologous stem cell transplantation for first relapse will change in practice may depend on regulatory approvals of these products, reviews by expert panels writing guidelines and pathways, the ability to manufacture products and deliver them to the appropriate patients in a timely manner, and society’s ability to pay the costs of these new agents.