Checkpoint Blockade in Melanoma Patients With Underlying Chronic Lymphocytic Leukemia.


Journal

Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
Titre abrégé: J Immunother
Pays: United States
ID NLM: 9706083

Informations de publication

Date de publication:
01 2021
Historique:
entrez: 8 12 2020
pubmed: 9 12 2020
medline: 27 11 2021
Statut: ppublish

Résumé

Chronic lymphocytic leukemia (CLL) is associated with immune dysfunction and an increased risk of melanoma. For patients with metastatic melanoma, immunotherapy with checkpoint blocking antibodies is a standard of care. In patients with concomitant CLL and metastatic melanoma, it is not known whether CLL might influence the antimelanoma efficacy or immune-related toxicities of immune checkpoint blockade. Fifteen patients with locally advanced or metastatic melanoma and a concomitant diagnosis of CLL who received pembrolizumab or ipilimumab with or without nivolumab for the treatment of their melanoma at Memorial Sloan Kettering Cancer Center between January 1, 2010, and January 1, 2017, were retrospectively identified. Clinical characteristics including absolute lymphocyte counts during therapy were recorded along with a response to treatment (objective radiographic response, progression-free survival, and adverse events) for each patient. Of 9 response-evaluable patients treated with ipilimumab, 3 (33%) had a partial response, 1 (11%) had stable disease, and 5 (56%) developed progressive disease. Objective tumor responses were also observed with single-agent therapy pembrolizumab and with combination therapy of nivolumab and ipilimumab. Grade 3 or 4 toxicity was observed in 6 of 15 patients (40%), including diarrhea, transaminitis, rash, and hemolytic anemia. Although our retrospective assessment was limited, there was no evidence that CLL responded to the checkpoint blockade. This case series demonstrates that ipilimumab, pembrolizumab, and combined ipilimumab and nivolumab therapies show clinical activity in patients with melanoma and concomitant CLL, at rates consistent with those previously reported. This population may warrant closer surveillance for hematologic immune-related toxicities such as autoimmune hemolytic anemia.

Identifiants

pubmed: 33290361
doi: 10.1097/CJI.0000000000000345
pii: 00002371-202101000-00002
pmc: PMC7727280
mid: NIHMS1638461
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Immune Checkpoint Inhibitors 0
Ipilimumab 0
Nivolumab 31YO63LBSN
pembrolizumab DPT0O3T46P

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9-15

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002384
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000457
Pays : United States

Références

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30.
Travis LB, Curtis RE, Hankey BF, et al. Second cancers in patients with chronic lymphocytic leukemia. J Natl Cancer Inst. 1992;84:1422–1427.
Hisada M, Biggar RJ, Greene MH, et al. Solid tumors after chronic lymphocytic leukemia. Blood. 2001;98:1979–1981.
Morton LM, Curtis RE, Linet MS, et al. Second malignancy risks after non-Hodgkin’s lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol. 2010;28:4935–4944.
Famenini S, Martires KJ, Zhou H, et al. Melanoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma. J Am Acad Dermatol. 2015;72:78–84.
Christopoulos P, Pfeifer D, Bartholome K, et al. Definition and characterization of the systemic T-cell dysregulation in untreated indolent B-cell lymphoma and very early CLL. Blood. 2011;117:3836–3846.
Hamblin AD, Hamblin TJ. The immunodeficiency of chronic lymphocytic leukaemia. Br Med Bull. 2008;87:49–62.
Beyer M, Kochanek M, Darabi K, et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood. 2005;106:2018–2025.
Motta M, Rassenti L, Shelvin BJ, et al. Increased expression of CD152 (CTLA-4) by normal T lymphocytes in untreated patients with B-cell chronic lymphocytic leukemia. Leukemia. 2005;19:1788–1793.
Frydecka I, Kosmaczewska A, Bocko D, et al. Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia. Br J Cancer. 2004;90:2042–2048.
Ramsay AG, Clear AJ, Fatah R, et al. Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer. Blood. 2012;120:1412–1421.
Riches JC, Davies JK, McClanahan F, et al. T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production. Blood. 2013;121:1612–1621.
McClanahan F, Hanna B, Miller S, et al. PD-L1 checkpoint blockade prevents immune dysfunction and leukemia development in a mouse model of chronic lymphocytic leukemia. Blood. 2015;126:203–211.
Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723.
Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–2532.
Younes A, Brody J, Carpio C, et al. Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Lancet Haematol. 2019;6:e67–e78.
Archibald WJ, Meacham PJ, Williams AM, et al. Management of melanoma in patients with chronic lymphocytic leukemia. Leuk Res. 2018;71:43–46.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–247.
Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–2526.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:1345–1356.
Visco C, Barcellini W, Maura F, et al. Autoimmune cytopenias in chronic lymphocytic leukemia. Am J Hematol. 2014;89:1055–1062.
Mauro FR, Foa R, Cerretti R, et al. Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features. Blood. 2000;95:2786–2792.
Pflug N, Bahlo J, Shanafelt TD, et al. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood. 2014;124:49–62.
Martens A, Wistuba-Hamprecht K, Yuan J, et al. Increases in absolute lymphocytes and circulating CD4+ and CD8+ T cells are associated with positive clinical outcome of melanoma patients treated with ipilimumab. Clin Cancer Res. 2016;22:4848–4858.
McKay LI, Cidlowski JAKufe DW, Pollock RE, Weichselbaum RR, Bast Jr RC, Gansler TS, Holland JF, Frei III E. Physiologic and pharmacologic effects of corticosteroids. Cancer Medicine, 6th ed. Hamilton, ON, Canada: BC Decker; 2003.
Ciszak L, Frydecka I, Wolowiec D, et al. Patients with chronic lymphocytic leukaemia (CLL) differ in the pattern of CTLA-4 expression on CLL cells: the possible implications for immunotherapy with CTLA-4 blocking antibody. Tumour Biol. 2016;37:4143–4157.
Mittal AK, Chaturvedi NK, Rohlfsen RA, et al. Role of CTLA4 in the proliferation and survival of chronic lymphocytic leukemia. PLoS One. 2013;8:e70352.
Joshi AD, Hegde GV, Dickinson JD, et al. ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia. Clin Cancer Res. 2007;13(pt 1):5295–5304.
Kosmaczewska A, Ciszak L, Suwalska K, et al. CTLA-4 overexpression in CD19+/CD5+ cells correlates with the level of cell cycle regulators and disease progression in B-CLL patients. Leukemia. 2005;19:301–304.
Ding W, LaPlant BR, Call TG, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017;129:3419–3427.
Ding W, Le-Rademacher J, Call TG, et al. PD-1 Blockade With Pembrolizumab in Relapsed CLL Including Richter’s Transformation: An Updated Report from a Phase 2 Trial (MC1485). San Diego, CA: American Society of Hematology; 2016.

Auteurs

James W Smithy (JW)

Melanoma and Immunotherapeutics Service, Department of Medicine.

Matthew J Pianko (MJ)

Rogel Cancer Center, University of Michigan, Ann Arbor, MI.

Colleen Maher (C)

Melanoma and Immunotherapeutics Service, Department of Medicine.
Ludwig Collaborative and Swim Across America Laboratory.

Michael A Postow (MA)

Melanoma and Immunotherapeutics Service, Department of Medicine.
Weill Cornell Medical College, New York, NY.

Alexander N Shoushtari (AN)

Melanoma and Immunotherapeutics Service, Department of Medicine.
Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center.
Weill Cornell Medical College, New York, NY.

Parisa Momtaz (P)

Melanoma and Immunotherapeutics Service, Department of Medicine.
Weill Cornell Medical College, New York, NY.

Paul B Chapman (PB)

Melanoma and Immunotherapeutics Service, Department of Medicine.
Weill Cornell Medical College, New York, NY.

Jedd D Wolchok (JD)

Melanoma and Immunotherapeutics Service, Department of Medicine.
Ludwig Collaborative and Swim Across America Laboratory.
Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center.
Weill Cornell Medical College, New York, NY.

Jae H Park (JH)

Leukemia Service, Department of Medicine.
Weill Cornell Medical College, New York, NY.

Margaret K Callahan (MK)

Melanoma and Immunotherapeutics Service, Department of Medicine.
Ludwig Collaborative and Swim Across America Laboratory.
Weill Cornell Medical College, New York, NY.

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