Ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) regimen for chronic lymphocytic leukemia (CLL) with mutated IGHV and without TP53 aberrations

Autor: Zeev Estrov, Prithviraj Bose, Varsha Gandhi, Jan A. Burger, Xuemei Wang, Naveen Garg, Rashmi Kanagal-Shamanna, Naveen Pemmaraju, Philip A. Thompson, Ana Ayala, Hagop M. Kantarjian, Koji Sasaki, Keyur P. Patel, Tapan M. Kadia, Alessandra Ferrajoli, Susan O'Brien, Elias Jabbour, Gautam Borthakur, Koichi Takahashi, Marina Konopleva, Wanda Lopez, Michael J. Keating, Wei Wang, William G. Wierda, Nitin Jain, Jeffrey L. Jorgensen, William Plunkett, Sa Wang
Rok vydání: 2021
Předmět:
Adult
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Cyclophosphamide
Chronic lymphocytic leukemia
Immunoglobulin Variable Region
Neutropenia
Antibodies
Monoclonal
Humanized
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Piperidines
Obinutuzumab
Chemoimmunotherapy
hemic and lymphatic diseases
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Biomarkers
Tumor
medicine
Humans
Aged
business.industry
Adenine
Hematology
Middle Aged
Prognosis
medicine.disease
Leukemia
Lymphocytic
Chronic
B-Cell
Fludarabine
Survival Rate
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Ibrutinib
Mutation
Female
Tumor Suppressor Protein p53
Immunoglobulin Heavy Chains
business
IGHV@
Vidarabine
Follow-Up Studies
medicine.drug
Zdroj: Leukemia. 35:3421-3429
ISSN: 1476-5551
0887-6924
Popis: Chemoimmunotherapy with combined fludarabine, cyclophosphamide and rituximab (FCR) has been an effective treatment for patients with chronic lymphocytic leukemia (CLL). We initiated a phase II trial for previously untreated patients with CLL with mutated IGHV and absence of del(17p)/TP53 mutation. Patients received ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) for three cycles. Patients who achieved complete remission (CR)/CR with incomplete count recvoery (CRi) with marrow undetectable measurable residual disease (U-MRD) received additional nine cycles of ibrutinib with three cycles of obinutuzumab; all others received nine additional cycles of ibrutinib and obinutuzumab. Patients in marrow U-MRD remission after cycle 12 discontinued all treatment, including ibrutinib. Forty-five patients were treated. The median follow-up is 41.3 months. Among the total 45 treated patients, after three cycles, 38% achieved CR/CRi and 87% achieved marrow U-MRD. After cycle 12, the corresponding numbers were 67% and 91%, respectively. Overall, 44/45 (98%) patients achieved marrow U-MRD as best response. No patient had CLL progression. The 3-year progression-free survival (PFS) and overall survival (OS) were 98% and 98%, respectively. Per trial design, all patients who completed cycle 12 discontinued ibrutinib, providing for a time-limited therapy. Grade 3-4 neutropenia and thrombocytopenia occurred in 58% and 40% patients, respectively. The iFCG regimen with only 3 cycles of chemotherapy is an effective, time-limited regimen for patients with CLL with mutated IGHV and without del(17p)/TP53 mutation.
Databáze: OpenAIRE
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