Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia: A cross-trial comparison of phase 3 studies

T Robak, JA Burger, A Tedeschi, PM Barr, C Owen, O Bairey, P Hillmen, D Simpson, S Grosicki, S Devereux, H McCarthy, SE Coutre, H Quach, G Gaidano, Z Maslyak, DA Stevens, C Moreno, DS Gill, IW Flinn, JG GribbenA Mokatrin, M Cheng, L Styles, DF James, TJ Kipps, P Ghia

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Abstract

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. © 2018 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)1402-1410
Number of pages9
JournalAmerican Journal of Hematology
Volume93
Issue number11
DOIs
Publication statusPublished - 2018

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    Robak, T., Burger, JA., Tedeschi, A., Barr, PM., Owen, C., Bairey, O., Hillmen, P., Simpson, D., Grosicki, S., Devereux, S., McCarthy, H., Coutre, SE., Quach, H., Gaidano, G., Maslyak, Z., Stevens, DA., Moreno, C., Gill, DS., Flinn, IW., ... Ghia, P. (2018). Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia: A cross-trial comparison of phase 3 studies. American Journal of Hematology, 93(11), 1402-1410. https://doi.org/10.1002/ajh.25259