Ibrutinib monotherapy in relapsed or refractory, transformed diffuse large B-cell lymphoma

Abstract Background Histological transformation to diffuse large B-cell lymphoma (tDLBCL) occurs in a significant proportion of indolent lymphomas. However, few studies of novel agents inform its management, particularly when relapsed after or refractory (R/R) to prior treatment. Patients and Methods We prospectively evaluated ibrutinib monotherapy in pathologically documented R/R tDLBCL in a single-arm study. The primary endpoint was overall response rate (ORR). Results Twenty patients who had received a median 4 (range 2–9) prior lines of therapy overall [median 2.5 (range 1–9) for tDLBCL] were treated. ORR was 35%, including complete responses in 15%. Median progression-free survival and overall survival were 4.1 months (95% CI, 2.4 – 6.2) and 22.4 months (95% CI 7.5 – NR), respectively. Disease control > 2 months was seen in 75% and > 1 year in 15%. Response was associated with either low tumor bulk or low metabolic tumor volume (p = 0.05) but not with antecedent lymphoma histology (p = 1.0). Treatment-related adverse events were consistent with prior studies of ibrutinib. Conclusions Ibrutinib showed low toxicity and meaningful efficacy in R/R tDLBCL, including short term disease control in most cases. Results demonstrate the potential utility of ibrutinib in this challenging clinical setting, including as a potential bridge to more definitive treatments.