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

Research output: Contribution to journalArticle

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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B-Cell Chronic Lymphocytic Leukemia
Chlorambucil
Disease-Free Survival
Therapeutics
Cyclophosphamide
PCI 32765
Survival
Hematology
Neutropenia
Lymph Nodes
Rituximab
Safety
Drug Therapy
Infection

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Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia: A cross-trial comparison of phase 3 studies. / 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; Gribben, JG; Mokatrin, A; Cheng, M; Styles, L; James, DF; Kipps, TJ; Ghia, P.

In: American Journal of Hematology, Vol. 93, No. 11, 2018, p. 1402-1410.

Research output: Contribution to journalArticle

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, Gribben, JG, Mokatrin, A, Cheng, M, Styles, L, James, DF, Kipps, TJ & 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, vol. 93, no. 11, pp. 1402-1410. https://doi.org/10.1002/ajh.25259
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 ; Gribben, JG ; Mokatrin, A ; Cheng, M ; Styles, L ; James, DF ; Kipps, TJ ; Ghia, P. / Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia: A cross-trial comparison of phase 3 studies. In: American Journal of Hematology. 2018 ; Vol. 93, No. 11. pp. 1402-1410.
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AU - Robak, T

AU - Burger, JA

AU - Tedeschi, A

AU - Barr, PM

AU - Owen, C

AU - Bairey, O

AU - Hillmen, P

AU - Simpson, D

AU - Grosicki, S

AU - Devereux, S

AU - McCarthy, H

AU - Coutre, SE

AU - Quach, H

AU - Gaidano, G

AU - Maslyak, Z

AU - Stevens, DA

AU - Moreno, C

AU - Gill, DS

AU - Flinn, IW

AU - Gribben, JG

AU - Mokatrin, A

AU - Cheng, M

AU - Styles, L

AU - James, DF

AU - Kipps, TJ

AU - Ghia, P

PY - 2018

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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. © 2018 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

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. © 2018 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

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DO - 10.1002/ajh.25259

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VL - 93

SP - 1402

EP - 1410

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

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