TY - JOUR
T1 - Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia
T2 - A cross-trial comparison of phase 3 studies
AU - Robak, Tadeusz
AU - Burger, Jan A.
AU - Tedeschi, Alessandra
AU - Barr, Paul M.
AU - Owen, Carolyn
AU - Bairey, Osnat
AU - Hillmen, Peter
AU - Simpson, David
AU - Grosicki, Sebastian
AU - Devereux, Stephen
AU - McCarthy, Helen
AU - Coutre, Steven E.
AU - Quach, Hang
AU - Gaidano, Gianluca
AU - Maslyak, Zvenyslava
AU - Stevens, Don A.
AU - Moreno, Carol
AU - Gill, Devinder S.
AU - Flinn, Ian W.
AU - Gribben, John G.
AU - Mokatrin, Ahmad
AU - Cheng, Mei
AU - Styles, Lori
AU - James, Danelle F.
AU - Kipps, Thomas J.
AU - Ghia, Paolo
N1 - Publisher Copyright:
© 2018 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
PY - 2018/11
Y1 - 2018/11
N2 - Chemoimmunotherapy (CIT) and targeted therapy with single-agent ibrutinib are both recommended first-line treatments for chronic lymphocytic leukemia (CLL), although their outcomes have not been directly compared. Using ibrutinib data from the RESONATE-2 (PCYC-1115/1116) study conducted in patients ≥65 years without del(17p), we performed a cross-trial comparison with CIT data from published phase 3 studies in first-line treatment of CLL. Progression-free survival (PFS), overall survival (OS), and safety data for ibrutinib (median follow-up 35.7 months) were evaluated alongside available CIT data. CIT regimens included: fludarabine + cyclophosphamide + rituximab (CLL8, CLL10), bendamustine + rituximab (CLL10), obinutuzumab + chlorambucil and rituximab + chlorambucil (CLL11), and ofatumumab + chlorambucil (COMPLEMENT-1). Median age across studies was 61-74 years, with older populations receiving ibrutinib, obinutuzumab + chlorambucil, or rituximab + chlorambucil. Median follow-up varied across studies/regimens (range 14.5-37.4 months). Among all patients, PFS appeared longer with ibrutinib relative to CIT and OS appeared comparable. Relative to CIT studies that similarly excluded patients with del(17p) (CLL10) or enrolled older/less-fit patients (CLL11), PFS appeared favorable for ibrutinib in high-risk subgroups, including advanced disease, bulky lymph nodes, unmutated IGHV status, and presence of del(11q). Grade ≥ 3 infections ranged from 9% (ofatumumab + chlorambucil) to 40% (fludarabine + cyclophosphamide + rituximab), and was 25% with ibrutinib. Grade ≥ 3 neutropenia was 12% for ibrutinib and 26%-84% for CIT. Although definitive conclusions cannot be made due to inherent limitations of cross-trial comparisons, this report suggests that ibrutinib has a favorable benefit/risk profile and may potentially eliminate the need for chemotherapy in some patients. Randomized, comparative studies are needed to support these findings.
AB - Chemoimmunotherapy (CIT) and targeted therapy with single-agent ibrutinib are both recommended first-line treatments for chronic lymphocytic leukemia (CLL), although their outcomes have not been directly compared. Using ibrutinib data from the RESONATE-2 (PCYC-1115/1116) study conducted in patients ≥65 years without del(17p), we performed a cross-trial comparison with CIT data from published phase 3 studies in first-line treatment of CLL. Progression-free survival (PFS), overall survival (OS), and safety data for ibrutinib (median follow-up 35.7 months) were evaluated alongside available CIT data. CIT regimens included: fludarabine + cyclophosphamide + rituximab (CLL8, CLL10), bendamustine + rituximab (CLL10), obinutuzumab + chlorambucil and rituximab + chlorambucil (CLL11), and ofatumumab + chlorambucil (COMPLEMENT-1). Median age across studies was 61-74 years, with older populations receiving ibrutinib, obinutuzumab + chlorambucil, or rituximab + chlorambucil. Median follow-up varied across studies/regimens (range 14.5-37.4 months). Among all patients, PFS appeared longer with ibrutinib relative to CIT and OS appeared comparable. Relative to CIT studies that similarly excluded patients with del(17p) (CLL10) or enrolled older/less-fit patients (CLL11), PFS appeared favorable for ibrutinib in high-risk subgroups, including advanced disease, bulky lymph nodes, unmutated IGHV status, and presence of del(11q). Grade ≥ 3 infections ranged from 9% (ofatumumab + chlorambucil) to 40% (fludarabine + cyclophosphamide + rituximab), and was 25% with ibrutinib. Grade ≥ 3 neutropenia was 12% for ibrutinib and 26%-84% for CIT. Although definitive conclusions cannot be made due to inherent limitations of cross-trial comparisons, this report suggests that ibrutinib has a favorable benefit/risk profile and may potentially eliminate the need for chemotherapy in some patients. Randomized, comparative studies are needed to support these findings.
UR - http://www.scopus.com/inward/record.url?scp=85054559377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054559377&partnerID=8YFLogxK
U2 - 10.1002/ajh.25259
DO - 10.1002/ajh.25259
M3 - Article
C2 - 30129285
AN - SCOPUS:85054559377
SN - 0361-8609
VL - 93
SP - 1402
EP - 1410
JO - American journal of hematology
JF - American journal of hematology
IS - 11
ER -