title: Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study.
abstract: Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses.
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Narendranath
authors.initials: N
authors.lastname: Epperla
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Cashen
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Kwang W
authors.initials: KW
authors.lastname: Ahn
authors.affiliation: Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Oak
authors.affiliation: Division of Hematology and Oncology, West Virginia University, Morgantown, WV, USA.
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Kanate
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Calzada
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Jonathon B
authors.initials: JB
authors.lastname: Cohen
authors.affiliation: Department of Hematology and Oncology, Levine Cancer Institute/Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Farmer
authors.affiliation: Department of Hematology and Oncology, Levine Cancer Institute/Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Ghosh
authors.affiliation: Division of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tallarico
authors.affiliation: Division of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.affiliation: Bone Marrow Transplantation and Cell Therapy Program, University of Alabama, Birmingham, AL, USA.
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Costa
authors.affiliation: Division of Hematology and Oncology, University of Wisconsin, Madison, WI, USA.
authors.forename: Vaishalee P
authors.initials: VP
authors.lastname: Kenkre
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Parameswaran N
authors.initials: PN
authors.lastname: Hari
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Fenske
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine
keywords: Mantle cell lymphoma; ibrutinib; predictive factors; refractory; relapsed