TY - JOUR
T1 - Phase 2 study of ibrutinib in classic and variant hairy cell leukemia
AU - Rogers, Kerry A.
AU - Andritsos, Leslie A.
AU - Wei, Lai
AU - McLaughlin, Eric M.
AU - Ruppert, Amy S.
AU - Anghelina, Mirela
AU - Blachly, James S.
AU - Call, Timothy
AU - Chihara, Dai
AU - Dauki, Anees
AU - Guo, Ling
AU - Ivy, S. Percy
AU - James, Lacey R.
AU - Jones, Daniel
AU - Kreitman, Robert J.
AU - Lozanski, Gerard
AU - Lucas, David M.
AU - Ngankeu, Apollinaire
AU - Phelps, Mitch
AU - Ravandi, Farhad
AU - Schiffer, Charles A.
AU - Carson, William E.
AU - Jones, Jeffrey A.
AU - Grever, Michael R.
N1 - Funding Information:
The authors acknowledge members of The Ohio State University Multisite Clinical Trials Program, including Jennifer Sexton, Alison Neal, Rebecca Imboden, and Rana Roberts; members of The Ohio State University Clinical Trials Office, including Terri Hutchinson, for supporting this study; and Theresa Yu, Lieutenant, United States Public Health Service/National Cancer Institute for her contribution to this study. This work was supported, in part, by The Ohio State University Comprehensive Cancer Center, by grants from the National Institutes of Health, National Cancer Institute (UM1CA186712 and P30 CA016058), and by the Hairy Cell Leukemia Foundation. K.A.R. is a Scholar in Clinical Research of the Leukemia & Lymphoma Society (CDP 2331-20).
Funding Information:
This work was supported, in part, by The Ohio State University Comprehensive Cancer Center, by grants from the National Institutes of Health, National Cancer Institute (UM1CA186712 and P30 CA016058), and by the Hairy Cell Leukemia Foundation. K.A.R. is a Scholar in Clinical Research of the Leukemia & Lymphoma Society (CDP 2331-20).
Funding Information:
This study was a phase 2 multisite, open-label, single-agent study funded by the National Cancer Institute, and participating sites are listed in the supplemental Data. Ibrutinib is provided by the National Cancer Institute through an agreement with Pharmacyclics. All patients provided informed consent. The study was conducted according to the principles of the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice. The protocol was approved by the institutional review boards of all participating sites.
Publisher Copyright:
© 2021 American Society of Hematology
PY - 2021/6/24
Y1 - 2021/6/24
N2 - Hairy cell leukemia (HCL) is a rare B-cell malignancy, and there is a need for novel treatments for patients who do not benefit from purine analogs. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown, so we conducted a multisite phase 2 study of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate (ORR) at 32 weeks, and we also assessed response at 48 weeks and best response during treatment. Key secondary objectives were characterization of toxicity and determination of progression-free survival (PFS) and overall survival (OS). Thirty-seven patients were enrolled at 2 different doses (24 at 420 mg, 13 at 840 mg). The median duration of follow-up was 3.5 years (range, 0-5.9 years). The ORR at 32 weeks was 24%, which increased to 36% at 48 weeks. The best ORR was 54%. The estimated 36-month PFS was 73% and OS was 85%. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common: anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to patients with HCL with objective responses and results in prolonged disease control. Although the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable PFS suggests that ibrutinib may be beneficial in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01841723.
AB - Hairy cell leukemia (HCL) is a rare B-cell malignancy, and there is a need for novel treatments for patients who do not benefit from purine analogs. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown, so we conducted a multisite phase 2 study of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate (ORR) at 32 weeks, and we also assessed response at 48 weeks and best response during treatment. Key secondary objectives were characterization of toxicity and determination of progression-free survival (PFS) and overall survival (OS). Thirty-seven patients were enrolled at 2 different doses (24 at 420 mg, 13 at 840 mg). The median duration of follow-up was 3.5 years (range, 0-5.9 years). The ORR at 32 weeks was 24%, which increased to 36% at 48 weeks. The best ORR was 54%. The estimated 36-month PFS was 73% and OS was 85%. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common: anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to patients with HCL with objective responses and results in prolonged disease control. Although the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable PFS suggests that ibrutinib may be beneficial in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01841723.
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U2 - 10.1182/blood.2020009688
DO - 10.1182/blood.2020009688
M3 - Article
C2 - 33754642
AN - SCOPUS:85108412516
SN - 0006-4971
VL - 137
SP - 3473
EP - 3483
JO - Blood
JF - Blood
IS - 25
ER -