Ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (GA101) (iFCG) for previously untreated patients with chronic lymphocytic leukemia (CLL) with mutated IGHV and non-del (17p)
| Autor: | Alessandra Ferrajoli, Varsha Gandhi, William G. Wierda, Michael J. Keating, Nitin Jain, Jan A. Burger, Gautam Borthakur, Philip A. Thompson, Prithviraj Bose, Zeev Estrov, Hagop M. Kantarjian, William Plunkett, Susan O'Brien, Wanda Lopez |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Cyclophosphamide business.industry Chronic lymphocytic leukemia medicine.disease Fludarabine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Obinutuzumab 030220 oncology & carcinogenesis Internal medicine Ibrutinib Immunology medicine business IGHV@ 030215 immunology medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 35:7522-7522 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 7522 Background: Pts with mutated IGHV ( IGHV-M) have favorable long-term outcomes after FCR. Methods: We designed an investigator-initiated phase II trial with ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) for previously untreated pts with IGHV-M CLL (NCT02629809). The intent was to limit FC to 3 courses, potentially reducing short- and long-term toxicity, while maintaining efficacy through addition of ibrutinib and obinutuzumab. Key eligibility included age ≥18, IGHV-M, no del17p. Pts received 3 courses of iFCG. G-CSF was not mandated. Primary endpoint: CR/CRi with bone marrow (BM) MRD-neg (4-color flow-cytometry) after 3 courses of iFCG. Pts meeting primary endpoint received ibrutinib with obinutuzumab (iG) for C3-6, then ibrutinib C7-12. Pts not achieving primary endpoint received iG (C4-12). All pts who are MRD neg at 1 year will stop all therapy, including ibrutinib. Pts MRD+ at 1 year may continue ibrutinib. Historic C3 BM MRD-neg with FCR in IGHV-M 26% (Strati, Blood 2014). Target BM MRD-neg after iFCG x3 is 45%. Sample size 45. Results: 23 pts started treatment. Median age 59 yrs (25-71). Prognostic markers [del13q (n=17), negative (n=3); trisomy 12 (n=3)]. 18 pts completed 3 courses of iFCG and had initial response assessment (the remaining 5 pts too early). All 18 pts had a response; 14/18 (78%) achieved MRD-neg in BM at 3 month with 7/18 achieving CR/CRi (all MRD neg). No pt has progressed, and all but one continue to receive treatment. Of the 23 pts, 11 pts had G3-4 neutropenia and 5 pts had G3-4 thrombocytopenia. 4 pt had neutropenic fever. 1 pt who achieved MRD-neg CR developed pulmonary MAC infection, and declined further therapy. 1 pt had atrial fibrillation. G3 ALT developed in 3 pts. FC was dose reduced in 10 pts; ibrutinib dose-reduced in 2 pts. Conclusions: iFCG achieves high rate of MRD-neg remission after 3 courses. Pt enrollment continues, and updated results will be presented at the ASCO meeting. Clinical trial information: NCT02629809. [Table: see text] |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|