Ibrutinib Monotherapy in Relapsed or Refractory, Transformed Diffuse Large B-cell Lymphoma

Here, we prospectively investigate ibrutinib monotherapy in 20 patients with relapsed or refractory diffuse large B-cell lymphoma histologically transformed from indolent lymphoma. Objective responses were seen in 35%, with median progression-free survival of 4.1 months (95% confidence interval, 2.4-6.2 months). Ibrutinib shows favorable tolerability and promising activity in this setting that otherwise has limited established treatment options. Background: Histologic 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 patients with R/R tDLBCL in a single-arm study. The primary endpoint was overall response rate. Results: Twenty patients who had received a median of 4 (range, 2-9) prior lines of therapy overall (median, 2.5; range, 1-9 for tDLBCL) were treated. The overall response rate was 35%, including complete responses in 15%. The median progression-free survival and overall survival were 4.1 months (95% confidence interval, 2.4-6.2 months) and 22.4 months (95% confidence interval, 7.5 months to not reached), 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 = .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. Published by Elsevier Inc.

Automated summary

This prospective study investigated the efficacy of ibrutinib monotherapy in 20 patients with histologically transformed diffuse large B-cell lymphoma, showing objective responses in 35% of patients with a median progression-free survival of 4.1 months. Ibrutinib demonstrated favorable tolerability and promising activity in this setting with limited treatment options, suggesting its potential utility as a bridge to more definitive treatments.