Feasibility of combining the phosphatidylinositol 3-kinase inhibitor copanlisib with rituximab-based immunochemotherapy in patients with relapsed indolent B-cell lymphoma Journal Article
| Authors: | Matasar, M. J.; Dreyling, M.; Leppä, S.; Santoro, A.; Pedersen, M.; Buvaylo, V.; Fletcher, M.; Childs, B. H.; Zinzani, P. L. |
| Article Title: | Feasibility of combining the phosphatidylinositol 3-kinase inhibitor copanlisib with rituximab-based immunochemotherapy in patients with relapsed indolent B-cell lymphoma |
| Abstract: | 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. © 2021 The Author(s) |
| Keywords: | adult; cancer chemotherapy; clinical article; controlled study; treatment response; aged; prednisone; constipation; drug tolerability; fatigue; cancer recurrence; doxorubicin; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; monotherapy; recommended drug dose; side effect; treatment duration; rituximab; cancer immunotherapy; infection; multiple cycle treatment; neutrophil count; sensory neuropathy; anemia; mucosa inflammation; nausea; vomiting; bendamustine; cyclophosphamide; vincristine; waldenstroem macroglobulinemia; coughing; drug dose escalation; dyspnea; febrile neutropenia; fever; hyperglycemia; pruritus; rash; alanine aminotransferase; aspartate aminotransferase; hypokalemia; hypotension; prednisolone; b cell lymphoma; cd20 antigen; drug response; therapy delay; urinary tract infection; flu like syndrome; headache; leukocyte count; connective tissue disease; lung infection; gastrointestinal disease; follicular lymphoma; marginal zone lymphoma; allergic reaction; musculoskeletal disease; lymphocyte count; upper respiratory tract infection; platelet count; dysgeusia; decreased appetite; phase 3 clinical trial (topic); eosinophilia; phase iii; r-chop; human; male; female; article; copanlisib; clinical indicator; treatment interruption; alanine aminotransferase level; aspartate aminotransferase level; chronos-4; safety run-in |
| Journal Title: | Clinical Lymphoma, Myeloma and Leukemia |
| Volume: | 21 |
| Issue: | 11 |
| ISSN: | 2152-2650 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2021-11-01 |
| Start Page: | e886 |
| End Page: | e894 |
| Language: | English |
| DOI: | 10.1016/j.clml.2021.06.021 |
| PUBMED: | 34389273 |
| PROVIDER: | scopus |
| PMCID: | PMC9407680 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2021 -- Source: Scopus |
