Phase II Trial of Pembrolizumab After High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

Overview

Journal Blood Cancer Discov

Specialties Hematology
Oncology

Date 2021 Nov 15

PMID 34778801

Citations 39

Authors

Joshua F Zeidner

Benjamin G Vincent

Anastasia Ivanova

Dominic Moore

Karen P McKinnon

Alec D Wilkinson

Rupkatha Mukhopadhyay

Francesco Mazziotta

Hanna A Knaus

Matthew C Foster

Catherine C Coombs

Katarzyna Jamieson

Hendrik van Deventer

Jonathan A Webster

Gabrielle T Prince

Amy E DeZern

B Douglas Smith

Mark J Levis

Nathan D Montgomery

Leo Luznik

Jonathan S Serody

Ivana Gojo

Affiliations

Soon will be listed here.

Abstract

Significance: Immune-checkpoint blockade with pembrolizumab was tolerable and feasible after high-dose cytarabine in R/R AML, with encouraging clinical activity, particularly in refractory AML and those receiving treatment as first salvage regimen. Further study of pembrolizumab and other immune-checkpoint blockade strategies after cytotoxic chemotherapy is warranted in AML.. .

Citing Articles

The Emerging Role of CD8 T Cells in Shaping Treatment Outcomes of Patients with MDS and AML.

Tasis A, Spyropoulos T, Mitroulis I Cancers (Basel). 2025; 17(5).

PMID: 40075597 PMC: 11898900. DOI: 10.3390/cancers17050749.

Bone marrow immune cells and drug resistance in acute myeloid leukemia.

Zhang M, Yang Y, Liu J, Guo L, Guo Q, Liu W Exp Biol Med (Maywood). 2025; 250:10235.

PMID: 40008144 PMC: 11851207. DOI: 10.3389/ebm.2025.10235.

Acute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence.

Mazziotta F, Martin L, Eagan D, Bar M, Kinsella S, Paulson K medRxiv. 2025; .

PMID: 39763516 PMC: 11702715. DOI: 10.1101/2024.12.13.24318504.

T-cell immune cluster analysis using CyTOF identifies unique subgroups of patients with acute myeloid leukemia.

Badar T, Knutson K, Knutson K, Foran J, Foran J, Gangat N Blood Adv. 2024; 9(2):239-243.

PMID: 39571168 PMC: 11782860. DOI: 10.1182/bloodadvances.2024014553.

What have we learned about TP53-mutated acute myeloid leukemia?.

Shahzad M, Amin M, Daver N, Shah M, Hiwase D, Arber D Blood Cancer J. 2024; 14(1):202.

PMID: 39562552 PMC: 11576745. DOI: 10.1038/s41408-024-01186-5.

References

Ravandi F, Pierce S, Garcia-Manero G, Kadia T, Jabbour E, Borthakur G . Salvage Therapy Outcomes in a Historical Cohort of Patients With Relapsed or Refractory Acute Myeloid Leukemia. Clin Lymphoma Myeloma Leuk. 2020; 20(11):e871-e882. DOI: 10.1016/j.clml.2020.06.007. View

Postow M, Manuel M, Wong P, Yuan J, Dong Z, Liu C . Peripheral T cell receptor diversity is associated with clinical outcomes following ipilimumab treatment in metastatic melanoma. J Immunother Cancer. 2015; 3:23. PMC: 4469400. DOI: 10.1186/s40425-015-0070-4. View

Cader F, Hu X, Goh W, Wienand K, Ouyang J, Mandato E . A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma. Nat Med. 2020; 26(9):1468-1479. PMC: 9673009. DOI: 10.1038/s41591-020-1006-1. View

Dufva O, Polonen P, Bruck O, Keranen M, Klievink J, Mehtonen J . Immunogenomic Landscape of Hematological Malignancies. Cancer Cell. 2020; 38(3):380-399.e13. DOI: 10.1016/j.ccell.2020.06.002. View

Xu C, Fillmore C, Koyama S, Wu H, Zhao Y, Chen Z . Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell. 2014; 25(5):590-604. PMC: 4112370. DOI: 10.1016/j.ccr.2014.03.033. View

Ustun C, Miller J, Munn D, Weisdorf D, Blazar B . Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation?. Blood. 2011; 118(19):5084-95. PMC: 3217399. DOI: 10.1182/blood-2011-07-365817. View

Groschel S, Sanders M, Hoogenboezem R, Zeilemaker A, Havermans M, Erpelinck C . Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 2014; 125(1):133-9. PMC: 4334729. DOI: 10.1182/blood-2014-07-591461. View

Dolen Y, Esendagli G . Myeloid leukemia cells with a B7-2(+) subpopulation provoke Th-cell responses and become immuno-suppressive through the modulation of B7 ligands. Eur J Immunol. 2012; 43(3):747-57. DOI: 10.1002/eji.201242814. View

Kondo A, Yamashita T, Tamura H, Zhao W, Tsuji T, Shimizu M . Interferon-gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes. Blood. 2010; 116(7):1124-31. PMC: 3375140. DOI: 10.1182/blood-2009-12-255125. View

10.

Knaus H, Berglund S, Hackl H, Blackford A, Zeidner J, Montiel-Esparza R . Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy. JCI Insight. 2018; 3(21). PMC: 6238744. DOI: 10.1172/jci.insight.120974. View

11.

Carreau N, Pail O, Armand P, Merryman R, Advani R, Spinner M . Checkpoint Blockade Treatment May Sensitize Hodgkin Lymphoma to Subsequent Therapy. Oncologist. 2020; 25(10):878-885. PMC: 7543382. DOI: 10.1634/theoncologist.2020-0167. View

12.

Lastwika K, Wilson 3rd W, Li Q, Norris J, Xu H, Ghazarian S . Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer. Cancer Res. 2015; 76(2):227-38. DOI: 10.1158/0008-5472.CAN-14-3362. View

13.

Chen C, Liang C, Wang S, Chio C, Zhang Y, Zeng C . Expression patterns of immune checkpoints in acute myeloid leukemia. J Hematol Oncol. 2020; 13(1):28. PMC: 7118887. DOI: 10.1186/s13045-020-00853-x. View

14.

Lindsley R, Mar B, Mazzola E, Grauman P, Shareef S, Allen S . Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015; 125(9):1367-76. PMC: 4342352. DOI: 10.1182/blood-2014-11-610543. View

15.

Karanes C, Kopecky K, Head D, Grever M, HYNES H, Kraut E . A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res. 1999; 23(9):787-94. DOI: 10.1016/s0145-2126(99)00087-9. View

16.

Miller B, Sen D, Al Abosy R, Bi K, Virkud Y, LaFleur M . Subsets of exhausted CD8 T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol. 2019; 20(3):326-336. PMC: 6673650. DOI: 10.1038/s41590-019-0312-6. View

17.

Ravandi F, Ritchie E, Sayar H, Lancet J, Craig M, Vey N . Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015; 16(9):1025-1036. PMC: 4822512. DOI: 10.1016/S1470-2045(15)00201-6. View

18.

Litzow M, Wang X, Carroll M, Karp J, Ketterling R, Zhang Y . A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease. Am J Hematol. 2018; 94(1):111-117. PMC: 6298814. DOI: 10.1002/ajh.25333. View

19.

Zhou Q, Munger M, Highfill S, Tolar J, Weigel B, Riddle M . Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood. 2010; 116(14):2484-93. PMC: 2953885. DOI: 10.1182/blood-2010-03-275446. View

20.

Dohner H, Estey E, Amadori S, Appelbaum F, Buchner T, Burnett A . Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2009; 115(3):453-74. DOI: 10.1182/blood-2009-07-235358. View