Feasibility of Combining the Phosphatidylinositol 3-Kinase Inhibitor Copanlisib With Rituximab-Based Immunochemotherapy in Patients With Relapsed Indolent B-cell Lymphoma

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Matasar , M J , Dreyling , M , Leppä , S , Santoro , A , Pedersen , M , Buvaylo , V , Fletcher , M , Childs , B H & Zinzani , P L 2021 , ' Feasibility of Combining the Phosphatidylinositol 3-Kinase Inhibitor Copanlisib With Rituximab-Based Immunochemotherapy in Patients With Relapsed Indolent B-cell Lymphoma ' , Clinical Lymphoma, Myeloma and Leukemia , vol. 21 , no. 11 , pp. E886-E894 . https://doi.org/10.1016/j.clml.2021.06.021

Title: Feasibility of Combining the Phosphatidylinositol 3-Kinase Inhibitor Copanlisib With Rituximab-Based Immunochemotherapy in Patients With Relapsed Indolent B-cell Lymphoma
Author: Matasar, Matthew J.; Dreyling, Martin; Leppä, Sirpa; Santoro, Armando; Pedersen, Michael; Buvaylo, Viktoriya; Fletcher, Monique; Childs, Barrett H.; Zinzani, Pier Luigi
Contributor organization: Department of Oncology
HUS Comprehensive Cancer Center
University of Helsinki
Date: 2021-11
Language: eng
Number of pages: 9
Belongs to series: Clinical Lymphoma, Myeloma and Leukemia
ISSN: 2152-2650
DOI: https://doi.org/10.1016/j.clml.2021.06.021
URI: http://hdl.handle.net/10138/338049
Abstract: Combining oral PI3K inhibitors with immunochemotherapy for indolent B-cell lymphoma has been associated with toxicity. In the Phase III CHRONOS-4 safety run-in, 21 patients received intravenous copanlisib plus rituximab-based immunochemotherapy. There were no dose-limiting toxicities, and preliminary objective response rates were 90% to 100%. Copanlisib is the first PI3K inhibitor to demonstrate safe, tolerable, and effective combinability with immunochemotherapy, with evaluation ongoing. Background: When treating indolent B-cell lymphoma, combining continuously administered oral phosphatidylinositol 3-kinase (PI3K) inhibitors with immunochemotherapy has been associated with toxicity. CHRONOS-4 (Phase III; NCT02626455) investigates the intravenous, intermittently administered pan-class I PI3K inhibitor copanlisib in combination with rituximab plus bendamustine (R-B) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with relapsed indolent B-cell lymphoma. We report safety run-in results. Patients and Methods: Patients aged >= 18 years with relapsed CD20-positive indolent B-cell lymphoma received copanlisib (45 mg, increasing to 60 mg if no dose-limiting toxicities) weekly on an intermittent schedule with R-B or R-CHOP. Primary objective was to identify a recommended Phase III dose (RP3D). We also assessed objective response, safety, and tolerability. Results: Ten patients received copanlisib plus R-B and 11 received copanlisib plus R-CHOP. No dose-limiting toxicities were reported; RP3D was 60 mg. All patients had >= 1 treatment-emergent adverse event (TEAE), most commonly (all grade/grade 3/4) for copanlisib plus R-B: decreased neutrophil count (80%/50%), nausea (70%/0%), decreased platelet count (60%/10%), hyperglycemia (60%/50%); for copanlisib plus R-CHOP: hyperglycemia (82%/64%), hypertension (73%/64%), decreased neutrophil count (64%/64%). Two and 8 patients had serious TEAEs with copanlisib plus R-B and R-CHOP, respectively. Among evaluable patients, objective response rates were 90% (5 complete, 4 partial) and 100% (3 complete, 7 partial) with copanlisib plus R-B and R-CHOP, respectively. Conclusion: Copanlisib is the first PI3K inhibitor to demonstrate safe, tolerable, and effective combinability with immunochemotherapy in patients with relapsed indolent B-cell lymphoma at full dose (60 mg). Further evaluation is ongoing. (C) 2021 The Author(s). Published by Elsevier Inc.
Subject: Bendamustine
CHRONOS-4
Phase III
R-CHOP
Safety run-in
NON-HODGKIN-LYMPHOMA
RESPONSE ASSESSMENT
PI3K INHIBITORS
DOSE-ESCALATION
PHASE-I
MALIGNANCIES
3122 Cancers
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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