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A phase 1 study of lenalidomide and ibrutinib in combination with rituximab in relapsed and refractory CLL.

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Citation: Blood Advances. 2(7):762-768, 2018 Apr 10PMID: 29610115Institution: MedStar Washington Hospital CenterDepartment: Hematology and OncologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage] | *Leukemia, Lymphocytic, Chronic, B-Cell/dt [Drug Therapy] | *Salvage Therapy/mt [Methods] | Aged | Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects] | Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use] | Drug Administration Schedule | Female | Humans | Lenalidomide/ad [Administration & Dosage] | Leukemia, Lymphocytic, Chronic, B-Cell/co [Complications] | Male | Maximum Tolerated Dose | Middle Aged | Neutropenia/ci [Chemically Induced] | Progression-Free Survival | Pyrazoles/ad [Administration & Dosage] | Pyrimidines/ad [Administration & Dosage] | Recurrence | Remission Induction/mt [Methods] | Rituximab/ad [Administration & Dosage] | Salvage Therapy/ae [Adverse Effects]Year: 2018 ISSN:

2473-9529

Name of journal: Blood advancesAbstract: Attempts to improve upon the activity of ibrutinib in chronic lymphocytic leukemia (CLL) include the addition of targeted therapies. The combination of lenalidomide and rituximab demonstrated an overall response rate (ORR) of 66% with a complete response (CR) of 12% in the relapsed/refractory setting. Based on these data, we conducted a phase 1 study of rituximab (R), lenalidomide (L), and ibrutinib (I) in relapsed/refractory CLL. Patients received R 375 mg/m<sup>2</sup> cycles 1 to 6 day 1, L on cycles 1 to 12 days 1 to 21, and I until disease progression. Dose escalation used a standard 3+3 design from a dose level (DL) of L 5 mg (DL1) and increasing to 15 mg (DL3) for a total of 3 dose levels. Twelve patients were enrolled; there were 2 dose-limiting toxicities of grade 4 neutropenia at DL3; thus, DL2 was the recommended phase 2 dose. A high incidence of sustained grade 4 neutropenia occurred at all dose levels, prompting study withdrawal in 5 patients, despite growth factor support. The ORR was 67%; ORR at the RP2D was 100% (1 CR). The 12-month progression-free survival at the RP2D was 83%. Preliminary efficacy data with the triplet did not appear superior to prior reports of the rituximab-lenalidomide doublet or single-agent ibrutinib. Given these findings and the sustained neutropenia, this regimen was not pursued. The study was registered at www.clinicaltrials.gov as #NCT02200848.Copyright (c) 2018 by The American Society of Hematology.All authors: Cheson BD, Khan N, Ramzi P, Skarbnik A, Trivedi N, Ujjani C, Wang HFiscal year: FY2018Digital Object Identifier:

https://dx.doi.org/10.1182/bloodadvances.2017015263

Date added to catalog: 2018-05-08

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Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	29610115	Available		29610115

Attempts to improve upon the activity of ibrutinib in chronic lymphocytic leukemia (CLL) include the addition of targeted therapies. The combination of lenalidomide and rituximab demonstrated an overall response rate (ORR) of 66% with a complete response (CR) of 12% in the relapsed/refractory setting. Based on these data, we conducted a phase 1 study of rituximab (R), lenalidomide (L), and ibrutinib (I) in relapsed/refractory CLL. Patients received R 375 mg/m<sup>2</sup> cycles 1 to 6 day 1, L on cycles 1 to 12 days 1 to 21, and I until disease progression. Dose escalation used a standard 3+3 design from a dose level (DL) of L 5 mg (DL1) and increasing to 15 mg (DL3) for a total of 3 dose levels. Twelve patients were enrolled; there were 2 dose-limiting toxicities of grade 4 neutropenia at DL3; thus, DL2 was the recommended phase 2 dose. A high incidence of sustained grade 4 neutropenia occurred at all dose levels, prompting study withdrawal in 5 patients, despite growth factor support. The ORR was 67%; ORR at the RP2D was 100% (1 CR). The 12-month progression-free survival at the RP2D was 83%. Preliminary efficacy data with the triplet did not appear superior to prior reports of the rituximab-lenalidomide doublet or single-agent ibrutinib. Given these findings and the sustained neutropenia, this regimen was not pursued. The study was registered at www.clinicaltrials.gov as #NCT02200848.

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