Ibrutinib associated with rituximab-platinum salt-based immunochemotherapy in B-cell lymphomas: Results of a phase 1b-II study of the LYSA group Journal Article
| Authors: | Bonnet, C.; Dupuis, J.; Tilly, H.; Lamy, T.; Fruchart, C.; le Gouill, S.; Thieblemont, C.; Morschhauser, F.; Casasnovas, O.; Bouabdallah, K.; Ghesquieres, H.; Van Den Neste, E.; André, M.; Cartron, G.; Salles, G. |
| Article Title: | Ibrutinib associated with rituximab-platinum salt-based immunochemotherapy in B-cell lymphomas: Results of a phase 1b-II study of the LYSA group |
| Abstract: | In the post-rituximab era, patients with relapsed/refractory non-Hodgkin B-cell lymphoma (R/R B-NHL) responding to a platinum salt-based salvage regimen can potentially be cured after intensification followed by autologous stem cell transplantation, with the quality of the response to salvage predicting survival. The Bruton tyrosine kinase inhibitor ibrutinib, given as monotherapy or combined with other molecules, has proven effective in numerous B-cell lymphomas. To evaluate the safety of the combination of ibrutinib, rituximab, dexamethasone, and cytarabine with either cisplatin (R-DHAP) or oxaliplatin (R-DHAOx), we conducted a multicenter Phase 1b-II study in transplant-eligible R/R B-NHL patients, with ibrutinib given using a 3-by-3 dose-escalation design. The combination of R-DHAP and ibrutinib (given from Day 1 to Day 21 of each cycle) was associated with dose-limiting hematological, infectious, and renal toxicities, while we were unable to reach a dose to recommend for Phase II. R-DHAOx could only be combined with a daily dosage of 280 mg ibrutinib when administered continuously. R-DHAP combined with intermittent ibrutinib administration (from Day 5 to Day 18) was found to be highly toxic. On the other hand, when this administration schedule was combined with R-DHAOx, ibrutinib dosing could be increased up to 560 mg but with relevant toxicities. Despite a strong rationale for combining ibrutinib and R-DHAP/R-DHAOx, as both target lymphoma B-cells by different mechanisms, this approach was limited by significant toxicities. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | adult; clinical article; controlled study; treatment outcome; treatment response; unclassified drug; overall survival; drug tolerability; histopathology; neutropenia; cancer recurrence; hepatitis; cisplatin; cancer combination chemotherapy; diarrhea; drug dose reduction; drug safety; hypophosphatemia; cytarabine; rituximab; antineoplastic agent; familial disease; cancer immunotherapy; progression free survival; controlled clinical trial; infection; mantle cell lymphoma; nephrotoxicity; anemia; bleeding; blood toxicity; heart disease; kidney disease; nausea; neuropathy; thrombocytopenia; vomiting; peripheral neuropathy; autologous stem cell transplantation; kidney failure; drug dose escalation; febrile neutropenia; hypokalemia; hyponatremia; b cell lymphoma; cardiotoxicity; sepsis; open study; cross-sectional study; skin disease; safety; antivirus agent; dermatitis; phase 1 clinical trial; genetic disorder; oxaliplatin; cotrimoxazole; alopecia; neurologic disease; gastrointestinal disease; hepatobiliary disease; atrial fibrillation; metabolic disorder; follicular lymphoma; cytopenia; virus pneumonia; hematologic disease; skin infection; bronchitis; epigastric pain; multiple organ failure; hypocalcemia; filgrastim; prostatitis; lymphatic system disease; pegfilgrastim; vein occlusion; diffuse large b cell lymphoma; stomach pain; aplasia; stomach hemorrhage; digestive system injury; ibrutinib; human; male; female; article; nodal marginal zone lymphoma; congenital disorder; r-dhaox; r-dhap; relapsed/refractory non-hodgkin b-cell lymphoma; cisplatin plus cytarabine plus dexamethasone plus rituximab; cytarabine plus dexamethasone plus oxaliplatin plus rituximab; transformed indolent lymphoma |
| Journal Title: | Cancers |
| Volume: | 14 |
| Issue: | 7 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2022-04-01 |
| Start Page: | 1761 |
| Language: | English |
| DOI: | 10.3390/cancers14071761 |
| PROVIDER: | scopus |
| PMCID: | PMC8997053 |
| PUBMED: | 35406532 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
