Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia

Mauricette Michallet; Peter Dreger; Mohamad Sobh; Linda Koster; Jennifer Hoek; Ariane Boumendil; Christof Scheid; Christopher P Fox; Gerald Wulf; William Krüger; Michel van Gelder; Paolo Corradini; Domenico Russo; Jakob Passweg; Hélène Schoemans; Wolfgang Bethge; Nicolaas Schaap; Jan Cornelissen; Paul Browne; Nadira Durakovic; Lutz Muller; Silvia Montoto; Nicolaus Kroger; Johannes Schetelig; French Cooperative Group for CLL, SFGM-TC, and the EBMT Chronic Malignancy and Lymphoma Working Parties

doi:10.1038/s41409-019-0742-7

Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia

Mauricette Michallet^*, Peter Dreger, Mohamad Sobh, Linda Koster, Jennifer Hoek, Ariane Boumendil, Christof Scheid, Christopher P Fox, Gerald Wulf, William Krüger, Michel van Gelder, Paolo Corradini, Domenico Russo, Jakob Passweg, Hélène Schoemans, Wolfgang Bethge, Nicolaas Schaap, Jan Cornelissen, Paul Browne, Nadira DurakovicLutz Muller, Silvia Montoto, Nicolaus Kroger, Johannes Schetelig, French Cooperative Group for CLL, SFGM-TC, and the EBMT Chronic Malignancy and Lymphoma Working Parties

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.

Original language	English
Pages (from-to)	884-890
Number of pages	7
Journal	Bone Marrow Transplantation
Volume	55
Issue number	5
Early online date	7 Nov 2019
DOIs	https://doi.org/10.1038/s41409-019-0742-7
Publication status	Published - May 2020

Keywords

STEM-CELL TRANSPLANTATION
HIGH-RISK CLL
TARGETING BTK
T-CELLS
OUTCOMES
FAILURE
DISEASE

Access to Document

10.1038/s41409-019-0742-7

Cite this

Michallet, M., Dreger, P., Sobh, M., Koster, L., Hoek, J., Boumendil, A., Scheid, C., Fox, C. P., Wulf, G., Krüger, W., van Gelder, M., Corradini, P., Russo, D., Passweg, J., Schoemans, H., Bethge, W., Schaap, N., Cornelissen, J., Browne, P., ... French Cooperative Group for CLL, SFGM-TC, and the EBMT Chronic Malignancy and Lymphoma Working Parties (2020). Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia. Bone Marrow Transplantation, 55(5), 884-890. https://doi.org/10.1038/s41409-019-0742-7

@article{ec6c12dc678243c7bf7b4a77082fcd1d,

title = "Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia",

abstract = "The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.",

keywords = "STEM-CELL TRANSPLANTATION, HIGH-RISK CLL, TARGETING BTK, T-CELLS, OUTCOMES, FAILURE, DISEASE",

author = "Mauricette Michallet and Peter Dreger and Mohamad Sobh and Linda Koster and Jennifer Hoek and Ariane Boumendil and Christof Scheid and Fox, {Christopher P} and Gerald Wulf and William Kr{\"u}ger and {van Gelder}, Michel and Paolo Corradini and Domenico Russo and Jakob Passweg and H{\'e}l{\`e}ne Schoemans and Wolfgang Bethge and Nicolaas Schaap and Jan Cornelissen and Paul Browne and Nadira Durakovic and Lutz Muller and Silvia Montoto and Nicolaus Kroger and Johannes Schetelig and {French Cooperative Group for CLL, SFGM-TC, and the EBMT Chronic Malignancy and Lymphoma Working Parties}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = may,

doi = "10.1038/s41409-019-0742-7",

language = "English",

volume = "55",

pages = "884--890",

journal = "Bone Marrow Transplantation",

issn = "0268-3369",

publisher = "Nature Publishing Group",

number = "5",

}

Michallet, M, Dreger, P, Sobh, M, Koster, L, Hoek, J, Boumendil, A, Scheid, C, Fox, CP, Wulf, G, Krüger, W, van Gelder, M, Corradini, P, Russo, D, Passweg, J, Schoemans, H, Bethge, W, Schaap, N, Cornelissen, J, Browne, P, Durakovic, N, Muller, L, Montoto, S, Kroger, N, Schetelig, J & French Cooperative Group for CLL, SFGM-TC, and the EBMT Chronic Malignancy and Lymphoma Working Parties 2020, 'Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia', Bone Marrow Transplantation, vol. 55, no. 5, pp. 884-890. https://doi.org/10.1038/s41409-019-0742-7

TY - JOUR

T1 - Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia

AU - Michallet, Mauricette

AU - Dreger, Peter

AU - Sobh, Mohamad

AU - Koster, Linda

AU - Hoek, Jennifer

AU - Boumendil, Ariane

AU - Scheid, Christof

AU - Fox, Christopher P

AU - Wulf, Gerald

AU - Krüger, William

AU - van Gelder, Michel

AU - Corradini, Paolo

AU - Russo, Domenico

AU - Passweg, Jakob

AU - Schoemans, Hélène

AU - Bethge, Wolfgang

AU - Schaap, Nicolaas

AU - Cornelissen, Jan

AU - Browne, Paul

AU - Durakovic, Nadira

AU - Muller, Lutz

AU - Montoto, Silvia

AU - Kroger, Nicolaus

AU - Schetelig, Johannes

AU - French Cooperative Group for CLL, SFGM-TC, and the EBMT Chronic Malignancy and Lymphoma Working Parties

PY - 2020/5

Y1 - 2020/5

N2 - The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.

AB - The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.

KW - STEM-CELL TRANSPLANTATION

KW - HIGH-RISK CLL

KW - TARGETING BTK

KW - T-CELLS

KW - OUTCOMES

KW - FAILURE

KW - DISEASE

U2 - 10.1038/s41409-019-0742-7

DO - 10.1038/s41409-019-0742-7

M3 - Article

C2 - 31700137

SN - 0268-3369

VL - 55

SP - 884

EP - 890

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

IS - 5

ER -