Disease burden and presence of at least 2 extranodal sites at either time of treatment (TT) or time of treatment decision (TD) was significantly associated with early disease progression among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, according to a study published in Blood Advances.1
CAR-T therapy is approved for patients with DLBCL who failed at least 2 prior lines of therapy, with clinical trial data suggesting complete response rates of approximately 30% to 40%. The purpose of this study was to determine if certain clinical, biological, or imaging characteristics at TT or TD were associated with relapse among patients with relapsed/refractory DLBCL after CAR T-cell therapy.
The multicenter, retrospective study included data from the medical charts of 116 consecutive patients with relapsed/refractory DLBCL between 2018 and 2020. The 2014 Cheson criteria was used to define relapse or progression of disease after CAR T-cell therapy, with biopsy of FDG-avid sites if feasible to ensure hypermetabolism on PET was not caused by inflammation due to the expansion of CAR T cells.
At TD, the median age was 60.7 years, with 36% of patients older than 65 years. The majority of patients had a good performance status (90%), 28% had at more than 2 extranodal sites, and 47% had elevated LDH. The International Prognostic Index (IPI) was low among 30.2% of patients, low-intermediate among 31%, high-intermediate among 24%, and high among 14%.
The majority of patients had DLBCL (80.2%), followed by transformed follicular lymphoma (14.7%), and primary B-cell lymphoma (5.2%). Treatment with >4 prior lines of therapy occurred in 30% of patients, with 26% who had undergone an autologous stem cell transplant.
Overall, the 6- and 12-month overall survival (OS) rates were 78.5% and 67%, respectively. The median progression-free survival was 7.4 months.
Relapse occurred among 47.4% of patients, with all but 1 relapse occurring within 4 months of CAR T cell infusion. Of the relapses, 49% occurred within the first month of treatment.
In multivariate analyses, relapse at any time was significantly associated with B symptoms (hazard ratio [HR], 1.85; 95% CI, 1.01-3.41; P =.0470) and elevated lactic dehydrogenase (LDH; HR, 2.04; 95% CI, 1.19-3.49; P =.0093) at TD. There was no association between relapse and age, lymphoma subtype, performance status, Ann Arbor stage, extranodal sites, or IPI status.
Early relapse after CAR-T therapy was significantly associated with performance status (HR, 2.95; 95% CI, 1.03-8.45; P =.044) and elevated LDH (HR, 9.61; 95% CI, 1.23-75.41; P =.031) at TD. Death after treatment was associated with having 2 or more extranodal sites at TD (HR, 4.17; 95% CI, 1.99-8.72; P =.00015).
At TT, relapse, early relapse, and death after CAR-T therapy were associated with having 2 or more extranodal sites, C-reactive protein, and total metabolic tumor volume.
The authors concluded that “risk factors identified for early progression at TD and at TT were extranodal involvement and lymphoma burden.”
Vercellino L, Di Blasi R, Kanoun S, et al. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. Published November 12, 2020. doi:10.1182/bloodadvances.2020003001