Solomon A Graf1, Ryan D Cassaday2, Karolyn Morris3, Jenna M Voutsinas4, Qian Vicky Wu4, Sanaz Behnia5, Ryan C Lynch6, Elizabeth Krakow6, Heather Rasmussen3, Thomas R Chauncey1, Sandra Kanan3, Lorinda Soma7, Stephen D Smith6, Ajay K Gopal8. 1. Division of Medical Oncology, University of Washington Medicine, Seattle, WA; Clinical Research Division, Fred Hutch Cancer Research Center, Seattle, WA; Department of Hospital and Specialty Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, WA. 2. Clinical Research Division, Fred Hutch Cancer Research Center, Seattle, WA; Division of Hematology. 3. Division of Medical Oncology, University of Washington Medicine, Seattle, WA. 4. Clinical Research Division, Fred Hutch Cancer Research Center, Seattle, WA. 5. Division of Nuclear Medicine, Department of Radiology. 6. Division of Medical Oncology, University of Washington Medicine, Seattle, WA; Clinical Research Division, Fred Hutch Cancer Research Center, Seattle, WA. 7. Department of Pathology, University of Washington Medicine, Seattle, WA. 8. Division of Medical Oncology, University of Washington Medicine, Seattle, WA; Clinical Research Division, Fred Hutch Cancer Research Center, Seattle, WA. Electronic address: agopal@uw.edu.
Abstract
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.
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.
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