ASH 2023: Durable Responses Observed with Valemetostat Improved Outcomes in Second-Line Treatment of Large B-Cell Lymphoma in the Era of CAR T-Cell Therapies

The treatment landscape of large B-cell lymphomas (LBCL) has changed dramatically in recent years, driven in part by the emergence of chimeric antigen receptor (CAR) T-cell therapies. To understand how these drugs have changed survival in patients with LBCL, investigators analyzed outcomes from the Lymphoma Epidemiology of Outcomes (LEO) Consortium for Real World Evidence (CReWE) study among participants with relapsed/ refractory LBCL in the second-line treatment setting.

LRF grantee Jean L. Koff, MD, MSc of Winship Cancer Institute was one of the main contributing investigators in this study. Results were presented by LRF Scientific Advisory Board member Loretta Nastoupil, MD of University of Texas MD Anderson Cancer Center.

Data for 1,523 patients who received second-line therapy between 2002 and 2022 were included in the analysis. From 2002 to 2010, before CAR T-cell therapies were available, 9% of patients received second-line therapy in a clinical trial setting. That number rose to 13% in the era of CAR T-cell clinical trials (2011 to 2017) and 17% following the approval of CAR T-cell therapies in the third-line setting and beyond. In total, 0.6% of patients from 2011 and 2017 and 13% of those from 2018 to 222 received second-line CAR T-cell therapy.

Among patients treated in 2002 to 2010, the 24-month event-free survival rate was 22%; this increased to 28% among those treated following the emergence of investigational CAR T-cell therapies. Among patients who received a second-line CAR T-cell therapy in clinical trials from 2011 to 2017, the 24-month event free survival rate was 50%. The 24 month overall survival rate increased over these intervals as well, particularly for those who received investigational CAR T-cell therapy. From 2011 to 2017, the 24-month overall survival rate was 47% among all patients, and 75% among those who received CAR T-cell therapy.

Survival rates in the second-line setting were similar from 2018 to 2022 as in the previous era (2011 to 2017), despite an increase in the number of patients receiving second-line CAR T-cell therapy. The investigators noted that additional analyses of factors associated with improved survival in these eras is still ongoing.

This study also included contributions from LRF SAB members James Cerhan, MD, PhD of Mayo Clinic, Rochester; Christopher Flowers, MD, MS of MD Anderson Cancer Center; Thomas Habermann, MD of Mayo Clinic, Rochester; Brad Kahl, MD of Washington University School of Medicine; Izidore Lossos, MD of University of Miami Health System; Peter Martin, MD of Weill Cornell Medicine; former SAB member Brian Link, MD of University of Iowa Carver College of Medicine; and LRF grantees Carla Casulo, MD of University of Rochester Medical Center; Dai Chihara, MD, PhD of MD Anderson Cancer Center; Jonathon B. Cohen, MD, MS of Winship Cancer Institute; Arushi Khurana, MBBS of Mayo Clinic, Rochester; and Matthew Maurer, D.M.Sc of Mayo Clinic, Rochester.