nach oben

Annals of Hematology

Erschienen in:

22.06.2017 | Review Article

PD-1 signaling and inhibition in AML and MDS

verfasst von: Faysal Haroun, Sade A. Solola, Samah Nassereddine, Imad Tabbara

Erschienen in: Annals of Hematology | Ausgabe 9/2017

Einloggen, um Zugang zu erhalten

Abstract

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.

Oran B, Weisdorf DJ (2012) Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica 97(12):1916–1924CrossRefPubMedPubMedCentral

Juliusson G, Lazarevic V, Hörstedt A-S, Hagberg O, Höglund M, Swedish Acute Leukemia Registry Group E et al (2012) Acute myeloid leukemia in the real world: why population-based registries are needed. Blood 119(17):3890–3899. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3358248 CrossRefPubMedPubMedCentral

Stone RM, Mandrekar S, Sanford BL, Geyer S, Bloomfield CD, Dohner K et al (2015) The multi-kinase inhibitor midostaurin (M) prolongs survival compared with placebo (P) in combination with daunorubicin (D)/cytarabine (C) induction (ind), high-dose C consolidation (consol), and as maintenance (maint) therapy in newly diagnosed acute myeloid leukemia (AML) patients (pts) age 18–60 with <em>FLT3</em> mutations (muts): an international prospective randomized (rand) P-controlled double-blind trial (CALGB 10603/RATIFY [Alliance]). Blood 126(23):6 LP-6 Available from: http://www.bloodjournal.org/content/126/23/6.abstract

Powles RL, Russell J, Lister TA, Oliver T, Whitehouse JM, Malpas J et al (1977) Immunotherapy for acute myelogenous leukaemia: a controlled clinical study 2 1/2 years after entry of the last patient. Br J Cancer [Internet] 35(3):265–272 Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025283/ CrossRefPubMedCentral

Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372(4):311–319CrossRefPubMed

Armand P (2015) Immune checkpoint blockade in hematologic malignancies. Blood 125(22):3393–3400 Available from: http://www.bloodjournal.org/content/125/22/3393.abstract CrossRefPubMed

Swerdlow SH, Campo E, Pileri SA, Lee Harris N, Stein H, Siebert R et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127:2375–2390

Deschler B, Lübbert M (2006) Acute myeloid leukemia: epidemiology and etiology. Cancer 107(9):2099–2107CrossRefPubMed

Crane MM, Strom SS, Halabi S, Berman EL, Fueger JJ, Spitz MR, et al. Correlation between selected environmental exposures and karyotype in acute myelocytic leukemia. Cancer Epidemiol Biomarkers &amp; Prev [Internet]. 1996 1;5(8):639 LP-644 Available from: http://cebp.aacrjournals.org/content/5/8/639.abstract

10.

Tamamyan G, Kadia T, Ravandi F, Borthakur G, Cortes J, Jabbour E, et al. Frontline treatment of acute myeloid leukemia in adults. Crit Rev Oncol / Hematol [Internet]. Elsevier; 2017 13;110:20–34. Available from: doi:10.1016/j.critrevonc.2016.12.004

11.

Gardin C, Chevret S, Pautas C, Turlure P, Raffoux E, Thomas X et al (2013) Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older. J Clin Oncol 31(3):321–327CrossRefPubMed

12.

Wiernik PH, Banks PL, Case DCJ, Arlin ZA, Periman PO, Todd MB, et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood [Internet]. 1992 Jan 15;79(2):313 LP-319 Available from: http://www.bloodjournal.org/content/79/2/313.abstract

13.

Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P et al (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med [Internet] 331(14):896–903. Available from: http://www.nejm.org/doi/pdf/10.1056/NEJM199410063311402 CrossRef

14.

Dail M, Yang L, Green C, Ma C, Robert A, Kadel EE, et al. Distinct patterns of PD-L1 and PD-L2 expression by tumor and non-tumor cells in patients with MM, MDS and AML. Blood [Internet]. 2016 Dec 1;128(22):1340 LP-1340 Available from: http://www.bloodjournal.org/content/128/22/1340.abstract

15.

Daver N, Basu S, Garcia-Manero G, Cortes JE, Ravandi F, Ning J, et al. Defining the immune checkpoint landscape in patients (pts) with acute myeloid leukemia (AML). Blood [Internet]. 2016 Dec 1;128(22):2900 LP-2900 Available from: http://www.bloodjournal.org/content/128/22/2900.abstract

16.

Wang S, Wang T, Li M, Cheng X, Li X (2016) Expression of microRNA miR-34a inhibits leukemia stem cells and its metastasis. Eur Rev Med Pharmacol Sci 20:2878–2883PubMed

17.

Zajac M, Zaleska J, Dolnik A, Siwiec A, Jankowska-Lecka O, Mlak R, et al. Analysis of the PD-1/PD-L1 axis points to association of unfavorable recurrent mutations with PD-L1 expression in AML. Blood [Internet]. 2016 Dec 1;128(22):1685 LP-1685 Available from: http://www.bloodjournal.org/content/128/22/1685.abstract

18.

Yang S, Huang XJ. The poorer-risk AML, the weaker immunologic surveillance?—higher PD-L1 expression on non-APL AML cells is associated with poorer risk status according to cytogenetics and molecular abnormailties. Blood [Internet]. 2016 Dec 1;128(22):1619 LP-1619 Available from: http://www.bloodjournal.org/content/128/22/1619.abstract

19.

Daver N, Basu S, Garcia-Manero G, Cortes JE, Ravandi F, Jabbour EJ, et al. Phase IB/II study of nivolumab in combination with azacytidine (AZA) in patients (pts) with relapsed acute myeloid leukemia (AML). Blood [Internet]. 2016 Dec 1;128(22):763 LP-763 Available from: http://www.bloodjournal.org/content/128/22/763.abstract

20.

Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood [Internet]. 2011 Feb 24;117(8):2307 LP-2318 Available from: http://www.bloodjournal.org/content/117/8/2307.abstract

21.

Frey NV, Porter DL (2010) Hematopoietic stem cell transplantation: ASBMT/CIBMTR 2010 tandem meeting highlights and discussion. Am J Hematol 85(7):519–523CrossRef

22.

Pasquini MC WZ, Pasquini M, Wang Z. Current use and outcome of hematopoietic stem cell transplantation. [Internet]. CIBMTR Summary Slides 2013. Available from: http://www.cibmtr.org/referencecenter/slidesreports/summaryslides/pages/index.aspx

23.

Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, et al. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J [Internet]. Nature Publishing Group; 2015 Jul 31;5(7):e330 Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526784/

24.

Merryman RW, Kim HT, Zinzani PL, Carlo-stella C, Ansell SM, Perales M, et al. Safety and ef fi cacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed / refractory lymphoma. 2017;129(10):1380–9.

25.

Haverkos BM, Schowinksy J, Kaplan J, Kamdar M, Kanate AS, Saad A, et al. Checkpoint blockade for treatment of relapsed lymphoma following allogeneic hematopoietic cell transplant: use may be complicated by onset of severe acute graft versus host disease. Blood [Internet]. 2016 Dec 1;128(22):1163 LP-1163 Available from: http://www.bloodjournal.org/content/128/22/1163.abstract

26.

Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A et al (2016) Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med [Internet] 375(2):143–153 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27410923 CrossRef

27.

Ma X, Does M, Raza A, Mayne ST (2007) Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109(8):1536–1542CrossRefPubMed

28.

Parikh A, Olnes MJ, Barrett AJ (2012) Immunomodulatory treatment of myelodysplastic syndromes: antithymocyte globulin, cyclosporine, and alemtuzumab. Semin Hematol [Internet] 49(4):304–311 Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157636/ CrossRef

29.

Saunthararajah Y, Nakamura R, Wesley R, Wang QJ, Barrett AJ. A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood [Internet]. 2003 Oct 3;102(8):3025 LP-3027 Available from: http://www.bloodjournal.org/content/102/8/3025.abstract

30.

Fenaux P, Ades L (2013) How we treat lower-risk myelodysplastic syndromes. Blood 121(21):4280–4286CrossRefPubMed

31.

Sekeres MA, Cutler C (2014) How we treat higher-risk myelodysplastic syndromes. Blood 123:829–836CrossRefPubMed

32.

Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M et al (2011) A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with low−/intermediate-1-risk myelodysplastic syndromes with del5q. Blood 118(14):3765–3776CrossRefPubMed

33.

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A et al (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol [Internet] 10(3):223–232 Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086808/ CrossRef

34.

Kantarjian H, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R, Shen L, Nimer SD, Leavitt R, Raza A, Saba HIJP (2006) Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer [Internet] 106(8):1794 Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=cctr&NEWS=N&AN=CN-00563257 CrossRef

35.

Wolff F, Leisch M, Greil R, Risch A, Pleyer L (2017) The double-edged sword of (re)expression of genes by hypomethylating agents: from viral mimicry to exploitation as priming agents for targeted immune checkpoint modulation. Cell Commun Signal [Internet] 15(1):13 Available from: http://biosignaling.biomedcentral.com/articles/10.1186/s12964-017-0168-z CrossRef

36.

Coats T, Smith A E, Mourikis TP, Irish JM, Kordasti S, Mufti GJ. Mass cytometry reveals PD1 upregulation is an early step in MDS disease progression. Blood [Internet]. 2016 Dec 1;128(22):4296 LP-4296 Available from: http://www.bloodjournal.org/content/128/22/4296.abstract

37.

Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng Q-R et al (2014) Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia [Internet] 28(6):1280–1288 Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032802/ CrossRef

38.

Ørskov AD, Treppendahl MB, Skovbo A, Holm MS, Friis LS, Hokland M et al (2015) Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients: a rationale for combined targeting of PD-1 and DNA methylation. Oncotarget [Internet]. Impact Journals LLC 6(11):9612–9626 Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496243/

39.

Garcia-Manero G, Tallman MS, Martinelli G, Ribrag V, Yang H, Balakumaran A, et al. Pembrolizumab, a PD-1 Inhibitor, in patients with myelodysplastic syndrome (MDS) after failure of hypomethylating agent treatment. Blood [Internet]. 2016 Dec 1;128(22):345 LP-345 Available from: http://www.bloodjournal.org/content/128/22/345.abstract

40.

Garcia-Manero G, Daver NG, Montalban-Bravo G, Jabbour EJ, DiNardo CD, Kornblau SM, et al. A phase II study evaluating the combination of nivolumab (Nivo) or ipilimumab (Ipi) with azacitidine in Pts with previously treated or untreated myelodysplastic syndromes (MDS). Blood [Internet]. 2016 Dec 1;128(22):344 LP-344 Available from: http://www.bloodjournal.org/content/128/22/344.abstract

41.

Bally C et al (2013) Azacitidine in the treatment of therapy related myelodysplastic syndrome and acute myeloid leukemia (tMDS/AML): a report on 54 patients by the Groupe Francophone Des Myelodysplasies (GFM). Leuk Res 37(6):637–640CrossRefPubMed

42.

Porkka, Kimmo et al. An open-label, phase 1b, dose-escalation study (CA180-373) of dasatinib plus nivolumab, an investigational anti-programmed cell death 1 (PD-1) antibody, in patients (pts) with previously treated chronic myeloid leukemia (CML) [abstract]. In: ASCO 50^th Annual Meeting; 2014 May 30- Jun 3; Chicago, IL. J Clin Oncol 32: 5s, 2014. Abstarct nr TPS7119.

Titel: PD-1 signaling and inhibition in AML and MDS
verfasst von: Faysal Haroun
Sade A. Solola
Samah Nassereddine
Imad Tabbara
Publikationsdatum: 22.06.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 9/2017
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-017-3051-5

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

PD-1 signaling and inhibition in AML and MDS

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2017

Detection of the circulating tumor DNAs in angioimmunoblastic T- cell lymphoma

Lineage switch from B acute lymphoblastic leukemia to acute monocytic leukemia with persistent t(4;11)(q21;q23) and cytogenetic evolution under CD19-targeted therapy

Palliative home care for patients with advanced haematological malignancies—a multicenter survey

In Burkitt lymphoma patients who relapse after induction with a short-intensive chemoimmunotherapy protocol, aggressive salvage chemotherapy therapy is ineffective: a single-center retrospective study

ABO genotype-phenotype discrepancy due to chimerism resolved by clonal separation

Detection of human T-cell lymphotropic virus type I-specific cytotoxic T-cells may predict treatment responses in adult T-cell leukemia/lymphoma patients

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin