Evaluation of the clinicopathologic features of diffuse large B cell lymphoma after CD19-targeted CAR T-cell therapy emphasizing the potential diagnostic pitfalls.

ABSTRACT

Clinicopathologic data of 16 cases of DLBCL, NOS after CD19-targeted CAR T-cell therapy were retrospectively reviewed. Statistical analyses were performed to investigate the diagnostic agreement and indicate the relationship of the given types or their alterations (Group I versus Group II) to the prognosis. A total of 5 distinct histologic patterns were summarized. The CAR T cells were somewhat atypical, most of which were CD8 positive in the most cases (86.7%, 13/15), with a relatively high Ki-67 (60-90%). The rearrangement of BCR was demonstrated in all cases. The diagnostic test showed that the diagnostic accuracy in cases of types III (7%) and V (7%) was typically low; the diagnostic agreement in cases of type IV (for B, T, or nonlymphoma) and V (for T, or nonlymphoma) was consistently unsatisfactory. The rates of complete response (CR), partial response (PR), and progressive disease (PD) were 18.8% (3/16), 31.3% (5/16), 50% (8/16), respectively. In the follow-up, 25% (4/16) of cases experienced a recurrence and 31.3% (5/16) had died, of which 3 cases succumbed to the side effects. Group II had better disease-free survival (DFS, P=0.009). This study first described the pathologic features of DLBCL after CD19-targeted CAR T-cell therapy. Familiarity with these histologic features and combinations of medical history and genetic analyses facilitate avoiding misdiagnoses. Multiple biopsies are potentially helpful to estimate the treatment effects or prognosis, and stable alterations to any type of III to V, but not a single given one, may indicate a good prognosis.