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01-04-2018 | Review Article

Program death inhibitors in classical Hodgkin’s lymphoma: a comprehensive review

Author: Reyad Dada

Published in: Annals of Hematology | Issue 4/2018

Abstract

Cancer cells are able to induce immune system tolerance through different mechanisms. Recent achievements in the understanding of tumor microenvironment, invasion, and metastasizing have contributed to accelerated drug developments and approvals. Hodgkin lymphoma (HL) cells are the minority in a lymphocyte-rich microenvironment of HL tissue. The program death-1 (PD-1)/PD-ligand-1 checkpoint is one of the known effective pathways in classical HL to escape the immune system cells. The approval of PD-1 inhibitors in different cancer types with exciting response rates is truly revolutionizing our treatment armamentarium against cancer in general and classical HL in specific. Although the disease is one of the most curable tumors, we still need better outcome with more gentle treatment, especially for relapsed and refractory (r/r) patients. In this article, we review the current literature on immune checkpoint inhibitors and currently ongoing studies with nivolumab and pembrolizumab in r/r classical HL.

Ansell SM (2016) Hodgkin lymphoma: MOPP chemotherapy to PD-1 blockade and beyond. Am J Hematol 91(1):109–112. https://doi.org/10.1002/ajh.24226 CrossRefPubMed

Longo DL, Young RC, Wesley M, Hubbard SM, Duffey PL, Jaffe ES, DeVita VT Jr (1986) Twenty years of MOPP therapy for Hodgkin’s disease. J Clin Oncol 4(9):1295–1306. https://doi.org/10.1200/jco.1986.4.9.1295 CrossRefPubMed

Younes A, Connors JM, Park SI, Fanale M, O’Meara MM, Hunder NN, Huebner D, Ansell SM (2013) Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol 14(13):1348–1356. https://doi.org/10.1016/S1470-2045(13)70501-1 CrossRefPubMed

Diehl V, Sieber M, Ruffer U, Lathan B, Hasenclever D, Pfreundschuh M, Loeffler M, Lieberz D, Koch P, Adler M, Tesch H (1997) BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin’s disease. The German Hodgkin’s Lymphoma Study Group. Ann Oncol 8(2):143–148. https://doi.org/10.1023/A:1008294312741 CrossRefPubMed

Dada R, Zekri J, Al Saadi R (2016) Brentuximab vedotin in pretreated Hodgkin lymphoma patients: a systematic review and meta-analysis. Expert Opin Biol Ther 16(6):739–745. https://doi.org/10.1080/14712598.2016.1180362 CrossRefPubMed

Kumar A, Casulo C, Yahalom J, Schoder H, Barr PM, Caron P, Chiu A, Constine LS, Drullinsky P, Friedberg JW, Gerecitano JF, Hamilton A, Hamlin PA, Horwitz SM, Jacob AG, Matasar MJ, McArthur GN, McCall SJ, Moskowitz AJ, Noy A, Palomba ML, Portlock CS, Straus DJ, VanderEls N, Verwys SL, Yang J, Younes A, Zelenetz AD, Zhang Z, Moskowitz CH (2016) Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood 128(11):1458–1464. https://doi.org/10.1182/blood-2016-03-703470 CrossRefPubMedPubMedCentral

Rubinstein PG, Moore P, Henry DH, Ratner L, Sharon E, Noy A (2015) AMC-085: a pilot trial of AVD and Brentuximab Vedotin in the upfront treatment of stage II-IV HIV-associated Hodgkin lymphoma. A trial of the AIDS Malignancy Consortium. Blood 126 (23)

Ansell SM (2016) Nivolumab in the treatment of Hodgkin lymphoma. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-16-1387

Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372(4):311–319. https://doi.org/10.1056/NEJMoa1411087 CrossRefPubMed

10.

Timmerman J, Engert A, Younes A, Santoro A, Armand P, Fanale MA, Collins GP, Ratanatharathorn V, Kuruvilla J, Cohen JB, Savage KJ, Trneny M, De Boer JP, Shipp MA, Rodig SJ, Zinzani PL, Kato K, Sumbul A, Ansell A (2016) Checkmate 205 update with minimum 12-month follow up: a phase 2 study of nivolumab in patients with relapsed/refractory classical hodgkin lymphom. ASH Meeting, abstract 1110

11.

Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, Cohen JB, Collins G, Savage KJ, Trneny M, Kato K, Farsaci B, Parker SM, Rodig S, Roemer MG, Ligon AH, Engert A (2016) Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 17(9):1283–1294. https://doi.org/10.1016/S1470-2045(16)30167-X CrossRefPubMedPubMedCentral

12.

Zinzani PL, Engert A, Younes A, Santoro A, Ansell S, Timmerman J, Collins GP, Armand P, Savage KJ, Trneny M, Fanale M, Kuruvilla J, Cohen JB, Shipp M, Rodig S, Kato K, Sumbul A, Farsaci BA, Ratanatharathorn V (2016) Checkmate 205 Cohort C: Nivolumab in patients with classical Hodgkin lymphoma after brentuximab vedotin and autologous hematopoietic stem cell transplantation. International Hodgkin Lymphoma Symposium (ishl) Abstract, T022

13.

Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz CH (2016) Programmed Death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. https://doi.org/10.1200/JCO.2016.67.3467

14.

Moskowitz CH, Zinzani PL, Fanale MA, Armand P, Johnson NA, Radford JA, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, Tresckow B, Shipp MA, Gustafson E, Zhang Y, Ricart AD, Balakumaran A, Chen RW (2016) Pembrolizumab in relapsed/refractory classical hodgkin lymphoma: primary end point analysis of the phase 2 Keynote-087 Study. ASH Meeting, abstract 1107

15.

Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30(18):2183–2189. https://doi.org/10.1200/JCO.2011.38.0410 CrossRefPubMedPubMedCentral

16.

Maruyama D, Hatake K, Kinoshita T, Fukuhara N, Choi I, Taniwaki M, Ando K, Terui Y, Higuchi Y, Onishi Y, Abe Y, Kobayashi T, Shirasugi Y, Tobinai K (2017) Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Cancer Sci 108(5):1007–1012. https://doi.org/10.1111/cas.13230 CrossRefPubMedPubMedCentral

17.

Herrera AF, Bartlett NL, Ramchandren R, Vose JM, Moskowitz AJ, Feldman TA, LaCasce AS, Ansell SM, Moskowitz CH, Fenton K, Kato K, Fong A, Advani RH (2016) Preliminary results from a phase 1/2 study of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory hodgkin lymphoma. ASH Meeting, abstract 1105

18.

Diefenbach CS, Hong F, David KA, Cohen J, Robertson M, Advani R, Palmisiano ND, Ambinder RF, Kahl BS, Ansell S A Phase I (2016) Study with an expansion cohort of the combination of ipilimumab and nivolumab and brentuximab vedotin in patients with relapsed/refractory hodgkin lymphoma: a Trial of the ECOG-ACRIN Cancer Research Group (E4412 Arms D and E). ASH Meeting, abstract 1106

19.

Rathore B, Kadin ME (2010) Hodgkin’s lymphoma therapy: past, present, and future. Expert Opin Pharmacother 11(17):2891–2906. https://doi.org/10.1517/14656566.2010.515979 CrossRefPubMedPubMedCentral

20.

Gangadhar TC, Hamid O, Smith DC, Bauer TM, Wasser JS, Luke JJ, Balmanoukian AS, Kaufman DR, Zhao Y, Maleski J, Leopold L, Gajewski TF (2016) Preliminary results from a phase I/II study of epacadostat (incb024360) in combination with pembrolizumab in patients with selected advanced cancers. J Immunother Cancer 3(Suppl 2):O7CrossRef

21.

Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP (2013) Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med 210(7):1389–1402. https://doi.org/10.1084/jem.20130066 CrossRefPubMedPubMedCentral

22.

Sagiv-Barfi I, Kohrt HEK, Czerwinski DK, Ng PP, Chang BY, Levy R (2015) Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. P Natl Acad Sci USA 112(9):E966–E972. https://doi.org/10.1073/pnas.1500712112 CrossRef

23.

Baues C, Semrau R, Gaipl US, Brockelmann PJ, Rosenbrock J, Engert A, Marnitz S (2016) Checkpoint inhibitors and radiation treatment in Hodgkin’s lymphoma : new study concepts of the German Hodgkin Study Group. Strahlenther Onkol 193(2):95–99. https://doi.org/10.1007/s00066-016-1050-4 CrossRefPubMed

24.

Derer A, Deloch L, Rubner Y, Fietkau R, Frey B, Gaipl US (2015) Radio-immunotherapy-induced immunogenic cancer cells as basis for induction of systemic anti-tumor immune responses—pre-clinical evidence and ongoing clinical applications. Front Immunol 6:505. https://doi.org/10.3389/Fimmu.2015.00505 CrossRefPubMedPubMedCentral

25.

Hanna GG, Coyle VM, Prise KM (2015) Immune modulation in advanced radiotherapies: targeting out-of-field effects. Cancer Lett 368(2):246–251. https://doi.org/10.1016/j.canlet.2015.04.007 CrossRefPubMed

26.

Engert A, Taylor F, Bennett B, Hirji I, Cocks K, McDonald J, Mann E, Kato K, Cella D (2016) Patient subgroup analysis of quality-of-life outcomes in CheckMate 205, a phase 2 study of nivolumab in patients with classical Hodgkin lymphoma. ASH Meeting, December 2016, abstract 1831

27.

Herbaux C, Gauthier J, Brice P, Drumez E, Ysebaert L, Doyen H, Fornecker L, Bouabdallah K, Manson G, Ghesquieres H, Tabrizi R, Hermet E, Lazarovici J, Thiebaut-Bertrand A, Chauchet A, Demarquette H, Boyle E, Houot R, Yakoub-Agha I, Morschhauser F (2017) Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma. Blood 129(18):2471–2478. https://doi.org/10.1182/blood-2016-11-749556 CrossRefPubMed

28.

Weiler-Sagie M, Bushelev O, Epelbaum R, Dann EJ, Haim N, Avivi I, Ben-Barak A, Ben-Arie Y, Bar-Shalom R, Israel O (2010) (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med 51(1):25–30. https://doi.org/10.2967/jnumed.109.067892 CrossRefPubMed

29.

Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, Hoos A, Barrington SF, Armand P (2016) Refinement of the Lugano classification lymphoma response criteria in the era of immunomodulatory therapy. Blood 128(21):2489–2496. https://doi.org/10.1182/blood-2016-05-718528 CrossRefPubMed

30.

Chiou VL, Burotto M (2015) Pseudoprogression and immune-related response in solid tumors. J Clin Oncol 33(31):3541–3543. https://doi.org/10.1200/JCO.2015.61.6870 CrossRefPubMedPubMedCentral

31.

Hoos A, Wolchok JD, Humphrey RW, Hodi FS (2015) CCR 20th anniversary commentary: immune-related response criteria—capturing clinical activity in immuno-oncology. Clin Cancer Res 21(22):4989–4991. https://doi.org/10.1158/1078-0432.CCR-14-3128 CrossRefPubMed

32.

Dercle L, Seban RD, Lazarovici J, Schwartz L, Houot R, Ammari S, Danu A, Edeline V, Marabelle A, Ribrag V, Michot JM (2017) 18F-FDG PET and CT-scan detect new imaging patterns of response and progression in patients with Hodgkin lymphoma treated by anti-PD1 immune checkpoint inhibitor. J Nucl Med. https://doi.org/10.2967/jnumed.117.193011

33.

Ok CY, Young KH (2017) Targeting the programmed death-1 pathway in lymphoid neoplasms. Cancer Treat Rev 54:99–109. https://doi.org/10.1016/j.ctrv.2017.01.009 CrossRefPubMedPubMedCentral

34.

Paydas S, Bagir E, Seydaoglu G, Ercolak V, Ergin M (2015) Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma. Ann Hematol 94(9):1545–1552. https://doi.org/10.1007/s00277-015-2403-2 CrossRefPubMed

35.

Hamadani M, Balasubramanian S, Hari PN (2015) Ibrutinib in refractory classic Hodgkin’s lymphoma. N Engl J Med 373(14):1381–1382. https://doi.org/10.1056/NEJMc1505857 CrossRefPubMed

36.

Fehniger TA, Larson S, Trinkaus K, Siegel MJ, Cashen AF, Blum KA, Fenske TS, Hurd DD, Goy A, Schneider SE, Keppel CR, Wagner-Johnston ND, Carson KR, Bartlett NL (2011) A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood 118(19):5119–5125. https://doi.org/10.1182/blood-2011-07-362475 CrossRefPubMedPubMedCentral

37.

Meadows SA, Vega F, Kashishian A, Johnson D, Diehl V, Miller LL, Younes A, Lannutti BJ (2012) PI3Kdelta inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood 119(8):1897–1900. https://doi.org/10.1182/blood-2011-10-386763 CrossRefPubMed

38.

Guarini A, Minoia C, Giannoccaro M, Rana A, Iacobazzi A, Lapietra A, Raimondi A, Silvestris N, Gadaleta CD, Ranieri G (2012) mTOR as a target of everolimus in refractory/relapsed Hodgkin lymphoma. Curr Med Chem 19(7):945–954CrossRefPubMed

39.

Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, Fong A, Younes A (2016) Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 128(12):1562–1566. https://doi.org/10.1182/blood-2016-02-699850 CrossRefPubMedPubMedCentral

Title: Program death inhibitors in classical Hodgkin’s lymphoma: a comprehensive review
Author: Reyad Dada
Publication date: 01-04-2018
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 4/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-017-3226-0

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