Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells

Brian K Link; Clive S Zent; Ronald P Taylor; Sue E Blackwell; Margaret A Lindorfer; Suresh Veeramani; George J Weiner; Paul V Beum; Betsy LaPlant; Wenting Wu; Timothy G Call; Deborah A Bowen; Michael J Conte; Lori A Frederick; Nisar A Baig; David S Viswanatha; Thomas E Witzig

doi:10.1002/ajh.23737

$Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells$

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Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells

Brian K Link, Clive S Zent, Ronald P Taylor, Sue E Blackwell, Margaret A Lindorfer, Suresh Veeramani, George J Weiner, Paul V Beum, Betsy LaPlant, Wenting Wu, …

American journal of hematology, Vol.89(7), pp.757-765

07/2014

DOI: 10.1002/ajh.23737

PMCID: PMC4280857

PMID: 24723493

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Abstract

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analogue refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a phase II trial testing the efficacy and tolerability of a short duration regimen combining pentostatin, alemtuzumab, and low dose high frequency rituximab (PAR) designed to decrease the risk of treatment associated infections and limit loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n=36) or previously untreated with 17p13 deletion (17p13-)(n=3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional and eight patients had purine analogue refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy with only five (13%) patients having treatment limiting toxicity, and no treatment related deaths. Twenty-two (56%) patients responded to treatment with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression free survival was 7.2 months, time to next treatment 9.1 months, and overall survival 34.1 months. The majority of deaths (82%) were caused by progressive disease including transformed diffuse large B cell lymphoma (n=6). Correlative studies showed that low dose rituximab activates complement and NK cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that PAR is a tolerable and effective therapy for CLL and that low dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression.

trogocytosis

refractory

17p13 deletion

Chronic lymphocytic leukemia

CLL

SLL

alemtuzumab and low dose rituximab

small lymphocytic lymphoma

relapsed

TP53

p53

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Title: Subtitle: Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells
Creators: Brian K Link - Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City IA
Clive S Zent - Division of Hematology, Mayo Clinic, Rochester MN
Ronald P Taylor - Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville VA
Sue E Blackwell - Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City IA
Margaret A Lindorfer - Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville VA
Suresh Veeramani - Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City IA
George J Weiner - Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City IA
Paul V Beum - Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville VA
Betsy LaPlant - Department of Health Sciences Research, Mayo Clinic, Rochester MN
Wenting Wu - Department of Health Sciences Research, Mayo Clinic, Rochester MN
Timothy G Call - Division of Hematology, Mayo Clinic, Rochester MN
Deborah A Bowen - Division of Hematology, Mayo Clinic, Rochester MN
Michael J Conte - Division of Hematology, Mayo Clinic, Rochester MN
Lori A Frederick - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN
Nisar A Baig - Division of Hematology, Mayo Clinic, Rochester MN
David S Viswanatha - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN
Thomas E Witzig - Division of Hematology, Mayo Clinic, Rochester MN
Resource Type: Journal article
Publication Details: American journal of hematology, Vol.89(7), pp.757-765
DOI: 10.1002/ajh.23737
PMID: 24723493
PMCID: PMC4280857
NLM abbreviation: Am J Hematol
ISSN: 0361-8609
eISSN: 1096-8652
Grant note: DOI: 10.13039/100000054, name: National Cancer Institute, award: CA097274; DOI: 10.13039/100000054, name: National Cancer Institute, award: P30CA86862
Language: English
Date published: 07/2014
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984094520102771

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