TY - JOUR
T1 - Ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) regimen for chronic lymphocytic leukemia (CLL) with mutated IGHV and without TP53 aberrations
AU - Jain, Nitin
AU - Thompson, Philip
AU - Burger, Jan
AU - Ferrajoli, Alessandra
AU - Takahashi, Koichi
AU - Estrov, Zeev
AU - Borthakur, Gautam
AU - Bose, Prithviraj
AU - Kadia, Tapan
AU - Pemmaraju, Naveen
AU - Sasaki, Koji
AU - Konopleva, Marina
AU - Jabbour, Elias
AU - Garg, Naveen
AU - Wang, Xuemei
AU - Kanagal-Shamanna, Rashmi
AU - Patel, Keyur
AU - Wang, Wei
AU - Jorgensen, Jeffrey
AU - Wang, Sa
AU - Lopez, Wanda
AU - Ayala, Ana
AU - Plunkett, William
AU - Gandhi, Varsha
AU - Kantarjian, Hagop
AU - O’Brien, Susan
AU - Keating, Michael
AU - Wierda, William G.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41375-021-01280-8
DO - 10.1038/s41375-021-01280-8
M3 - Article
C2 - 34007049
AN - SCOPUS:85106315280
SN - 0887-6924
VL - 35
SP - 3421
EP - 3429
JO - Leukemia
JF - Leukemia
IS - 12
ER -