Identifying and treating candidates for checkpoint inhibitor therapies in multiple myeloma and lymphoma

References

• Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol. 2006;6:836–848.
   PubMed Web of Science ®Google Scholar
• Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39:98–106.
   PubMed Web of Science ®Google Scholar
• Jelinek T, Paiva B, Hajek R. Update on PD-1/PD-L1 inhibitors in multiple myeloma. Front Immunol. 2018;9:2431.
   PubMed Web of Science ®Google Scholar
• Matsuki E, Younes A. Checkpoint inhibitors and other immune therapies for hodgkin and non-hodgkin lymphoma. Curr Treat Options Oncol. 2016;17:31.
   PubMed Web of Science ®Google Scholar
• Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–1034.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wu L, Tian C, et al. PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas. Ann Hematol. 2018;97:229–237.
   PubMed Web of Science ®Google Scholar
• Jelinek T, Mihalyova J, Kascak M, et al. PD-1/PD-L1 inhibitors in haematological malignancies: update 2017. Immunology. 2017;152:357–371.
   PubMed Web of Science ®Google Scholar
• The Nobel prize in medicine 2018 awarded for discovery of CTLA-4 and PD-1 | ESMO [Internet]. [cited 2019 Sep 16]. Available from: https://www.esmo.org/Oncology-News/The-Nobel-Prize-in-Medicine-2018-Awarded-for-Discovery-of-CTLA-4-and-PD-1
   Google Scholar
• Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375–384.
   PubMed Web of Science ®Google Scholar
• Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379:2342–2350.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–1290.
   PubMed Web of Science ®Google Scholar
• Tahara M, Muro K, Hasegawa Y, et al. Pembrolizumab in Asia-Pacific patients with advanced head and neck squamous cell carcinoma: analyses from KEYNOTE-012. Cancer Sci. 2018;109:771–776.
   PubMed Web of Science ®Google Scholar
• Ansell S, Armand P, Timmerman JM, et al. Nivolumab in patients (Pts) with relapsed or refractory classical Hodgkin lymphoma (R/R cHL): clinical outcomes from extended follow-up of a phase 1 study (CA209-039). Blood. 2015;126:583.
   Web of Science ®Google Scholar
• Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 trial. J Clin Oncol. 2018;36:1428–1439.
   PubMed Web of Science ®Google Scholar
• Armand P, Shipp MA, Ribrag V, et al. Pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: long-term efficacy from the phase 1b Keynote-013 study. Blood. 2016;128:1108.
   Web of Science ®Google Scholar
• Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35:2125–2132.
   PubMed Web of Science ®Google Scholar
• Armand P, Rodig SJ, Melnichenko V, et al. Pembrolizumab in patients with relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL): data from the Keynote-013 and Keynote-170 studies. Blood. 2018;132:228.
   Google Scholar
• List of Anti-PD-1 monoclonal antibodies (anti-programmed cell death-1 (PD-1) monoclonal antibodies) [Internet]. Drugs.com. [cited 2019 Sep 17]. Available from: https://www.drugs.com/drug-class/anti-pd-1-monoclonal-antibodies.html
   Google Scholar
• Trinh S, Le A, Gowani S, et al. Management of immune-related adverse events associated with immune checkpoint inhibitor therapy: a minireview of current clinical guidelines. Asia-Pac J Oncol Nurs. 2019;6:154–160.
   PubMed Web of Science ®Google Scholar
• Martinez-Calle N, Rodriguez-Otero P, Villar S, et al. Anti-PD1 associated fulminant myocarditis after a single pembrolizumab dose: the role of occult pre-existing autoimmunity. Haematologica. 2018;103:e318-e321. haematol.2017.185777
   PubMed Web of Science ®Google Scholar
• Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2017;28:iv119–iv142.
   PubMed Web of Science ®Google Scholar
• Kazandjian D. Multiple myeloma epidemiology and survival: a unique malignancy. Semin Oncol. 2016;43:676–681.
   PubMed Web of Science ®Google Scholar
• Maluskova D, Svobodová I, Kucerova M, et al. Epidemiology of multiple myeloma in the Czech Republic. Klin Onkol Cas Ceske Slov Onkol Spolecnosti. 2017;30:35–42.
   PubMedGoogle Scholar
• Jelinek T, Hajek R. PD-1/PD-L1 inhibitors in multiple myeloma: the present and the future. Oncoimmunology. 2016;5:e1254856.
   PubMed Web of Science ®Google Scholar
• Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2017;28:iv52–iv61.
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–1331.
   PubMed Web of Science ®Google Scholar
• Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–631.
   PubMed Web of Science ®Google Scholar
• Moreno L, Perez C, Zabaleta A, et al. The mechanism of action of the anti-CD38 monoclonal antibody isatuximab in multiple myeloma. Clin Cancer Res Off J Am Assoc Cancer Res. 2019;25:3176–3187.
   PubMed Web of Science ®Google Scholar
• Castella M, Fernández de Larrea C, Martín-Antonio B. Immunotherapy: a novel era of promising treatments for multiple myeloma. Int J Mol Sci [Internet]. 2018 [cited 2019 Sep 17];19:3613. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274949/
   PubMed Web of Science ®Google Scholar
• Görgün G, Samur MK, Cowens KB, et al. Lenalidomide enhances immune checkpoint blockade-induced immune response in multiple myeloma. Clin Cancer Res Off J Am Assoc Cancer Res. 2015;21:4607–4618.
   PubMed Web of Science ®Google Scholar
• Paiva B, Azpilikueta A, Puig N, et al. PD-L1/PD-1 presence in the tumor microenvironment and activity of PD-1 blockade in multiple myeloma. Leukemia. 2015;29:2110–2113.
   PubMed Web of Science ®Google Scholar
• Benson DM, Bakan CE, Mishra A, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibody. Blood. 2010;116:2286–2294.
   PubMed Web of Science ®Google Scholar
• Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol. 2016;34:2698–2704.
   PubMed Web of Science ®Google Scholar
• Ribrag V, Avigan DE, Green DJ, et al. Phase 1b trial of pembrolizumab monotherapy for relapsed/refractory multiple myeloma: KEYNOTE-013. Br J Haematol. 2019;186:e41–e44.
   PubMed Web of Science ®Google Scholar
• Ansell S, Gutierrez ME, Shipp MA, et al. A phase 1 study of nivolumab in combination with ipilimumab for relapsed or refractory hematologic malignancies (CheckMate 039). Blood. 2016;128:183.
   Web of Science ®Google Scholar
• Badros A, Hyjek E, Ma N, et al. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017;130:1189–1197.
   PubMed Web of Science ®Google Scholar
• Badros AZ, Ma N, Rapoport AP, et al. Long-term remissions after stopping pembrolizumab for relapsed or refractory multiple myeloma. Blood Adv. 2019;3:1658–1660.
   PubMed Web of Science ®Google Scholar
• Mateos M-V, Blacklock H, Schjesvold F, et al. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol [Internet]. 2019 [cited 2019 Aug 7]. Available from: https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30110-3/abstract
   Web of Science ®Google Scholar
• Usmani SZ, Schjesvold F, Oriol A, et al. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol [Internet]. 2019 [cited 2019 Jul 25];6:e448-e458. Available from: http://www.sciencedirect.com/science/article/pii/S2352302619301097
   PubMed Web of Science ®Google Scholar
• Smith E. Pembrolizumab plus lenalidomide and dexamethasone for the treatment of multiple myeloma: results from KEYNOTE-183, KEYNOTE-185 and KEYNOTE-023 [Internet]. 2019 [cited 2019 Aug 7]. Available from: https://multiplemyelomahub.com/medical-information/pembrolizumab-plus-lenalidomide-and-dexamethasone-for-the-treatment-of-multiple-myeloma-results-from-keynote-183-keynote-185-and-keynote-023
   Google Scholar
• Mateos M-V, Orlowski RZ, Ocio EM, et al. Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Br J Haematol [Internet]. 2019 [cited 2019 Aug 7]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.15946
   Web of Science ®Google Scholar
• Lonial S, Richardson PG, Reece DE, et al. CheckMate 602: an open-label, randomized, phase 3 trial of combinations of nivolumab, elotuzumab, pomalidomide and dexamethasone in relapsed/refractory multiple myeloma. J Clin Oncol. 2017;35:TPS8052–TPS8052.
   Web of Science ®Google Scholar
• Lonial S, Richardson P, Reece D, et al. CheckMate 602: a phase 3, open-label, randomized trial of combinations of nivolumab, elotuzumab, pomalidomide, and dexamethasone in relapsed or relapsed and refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2017;17:S330.
   Google Scholar
• FDA lifts partial clinical hold on CheckMate-602 trial in MM [Internet]. [cited 2019 Aug 7]. Available from: https://www.thepharmaletter.com/article/fda-lifts-partial-clinical-hold-on-checkmate-602-trial-in-mm
   Google Scholar
• Bezman NA, Kinder M, Jhatakia AD, et al. Abstract 1727: antitumor activity associated with dual targeting of CD38 and programmed death-1 (PD-1) pathways in preclinical models. Cancer Res. 2018;78:1727.
   Web of Science ®Google Scholar
• Cho HJ, Costa LJ, Davies FE, et al. Atezolizumab in combination with daratumumab with or without lenalidomide or pomalidomide: a phase Ib study in patients with multiple myeloma. Blood. 2018;132:597.
   Web of Science ®Google Scholar
• Phase A I/II study of isatuximab and cemiplimab immunotherapy in patients with recurrent or persistent multiple myeloma [Internet]. Meml. Sloan Kettering Cancer Cent. [cited 2019 Aug 7]. Available from: https://www.mskcc.org/cancer-care/clinical-trials/18-353
   Google Scholar
• Van Droogenbroeck J, Vlummens P, Lavi N, et al. Randomized, open-label, phase 2/3 study of daratumumab (DARA) with or without JNJ-63723283, an anti-PD-1 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2018;36:TPS8057–TPS8057.
   Web of Science ®Google Scholar
• Hamed RA, Bazarbachi AH, Malard F, et al. Current status of autologous stem cell transplantation for multiple myeloma. Blood Cancer J. 2019;9:44.
   PubMed Web of Science ®Google Scholar
• Pirogova O, Darskaya E, Porunova V, et al. Results of phase I/II study of nivolumab with autologous hematopoietic stem cell transplantation in multiple myeloma patients with suboptimal response to primary induction therapy [Internet]. EHA Libr. 2019 [cited 2019 Aug 2]. Available from: https://library.ehaweb.org/eha/2019/24th/267013/olga.pirogova.results.of.phase.i.ii.study.of.nivolumab.with.autologous.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dmultiple+myeloma%2Bpd-1
   Google Scholar
• D’Souza A, Hari P, Pasquini M, et al. A phase 2 study of pembrolizumab during lymphodepletion after autologous hematopoietic cell transplantation for multiple myeloma. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2019;25:1492–1497.
   PubMed Web of Science ®Google Scholar
• Biran N, Andrews T, Feinman R, et al. A phase II trial of the anti -PD-1 monoclonal antibody pembrolizumab (MK-3475) + lenalidomide + dexamethasone as post autologous stem cell transplant consolidation in patients with high-risk multiple myeloma. Blood. 2017;130:1831.
   Web of Science ®Google Scholar
• Skarbnik AP, Donato ML, Korngold R, et al. Safety and efficacy data for combined checkpoint inhibition with ipilimumab (Ipi) and nivolumab (Nivo) as consolidation following autologous stem cell transplantation (ASCT) for high-risk hematological malignancies — CPIT-001 trial. Blood. 2018;132:256.
   Web of Science ®Google Scholar
• Lesokhin AM, Chung DJ, Cho HJ, et al. Phase 1 study to evaluate the safety and efficacy of immunotherapy with tremelimumab and durvalumab in multiple myeloma patients receiving high dose chemotherapy and autologous stem cell transplant (HDT/ASCT) + peripheral blood lymphocyte (PBL) reinfusion. J Clin Oncol. 2017;35:TPS8051–TPS8051.
   Web of Science ®Google Scholar
• Benboubker L, Dimopoulos MA, Dispenzieri A, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371:906–917.
   PubMed Web of Science ®Google Scholar
• Usmani SZ, Schjesvold F, Oriol A, et al. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019;6:e448–e458.
   PubMed Web of Science ®Google Scholar
• Zelle-Rieser C, Thangavadivel S, Biedermann R, et al. T cells in multiple myeloma display features of exhaustion and senescence at the tumor site. J Hematol Oncol [Internet]. 2016 [cited 2020 Feb 9];9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093947/
   PubMed Web of Science ®Google Scholar
• Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–548.
   PubMed Web of Science ®Google Scholar
• Manasanch EE, Han G, Mathur R, et al. A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis. Blood Adv. 2019;3:2400–2408.
   PubMed Web of Science ®Google Scholar
• Ayers M, Lunceford J, Nebozhyn M, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127:2930–2940.
   PubMed Web of Science ®Google Scholar
• Huh J. Epidemiologic overview of malignant lymphoma. Korean J Hematol. 2012;47:92–104.
   PubMedGoogle Scholar
• Armitage JO, Gascoyne RD, Lunning MA, et al. Non-hodgkin lymphoma. Lancet. 2017;390:298–310.
   PubMed Web of Science ®Google Scholar
• Pianko MJ, Moskowitz AJ, Lesokhin AM. Immunotherapy of lymphoma and myeloma: facts and hopes. Clin Cancer Res Off J Am Assoc Cancer Res. 2018;24:1002–1010.
   PubMed Web of Science ®Google Scholar
• Goodman A, Patel SP, Kurzrock R. PD-1-PD-L1 immune-checkpoint blockade in B-cell lymphomas. Nat Rev Clin Oncol. 2017;14:203–220.
   PubMed Web of Science ®Google Scholar
• Swerdlow SH, Campo Güerri E, et al. Who classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: International Agency for Research on Cancer; 2017
   Google Scholar
• Eberle FC, Salaverria I, Steidl C, et al. Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations. Mod Pathol Off J U S Can Acad Pathol Inc. 2011;24:1586–1597.
   PubMed Web of Science ®Google Scholar
• Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018;131:68–83.
   PubMed Web of Science ®Google Scholar
• Roemer MGM, Advani RH, Ligon AH, et al. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34:2690–2697.
   PubMed Web of Science ®Google Scholar
• Younes A, Santoro A, Shipp M, et al. 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. 2016;17:1283–1294.
   PubMed Web of Science ®Google Scholar
• Nishijima TF, Shachar SS, Nyrop KA, et al. Safety and tolerability of PD-1/PD-L1 inhibitors compared with chemotherapy in patients with advanced cancer: a meta-analysis. Oncologist. 2017;22:470–479.
   PubMed Web of Science ®Google Scholar
• Herrera AF, Moskowitz AJ, Bartlett NL, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018;131:1183–1194.
   PubMed Web of Science ®Google Scholar
• Ansell SM, Bartlett NL, Chen RW, et al. Investigating safety and preliminary efficacy of AFM13 plus pembrolizumab in patients with relapsed/refractory Hodgkin lymphoma after brentuximab vedotin failure. Hematol Oncol. 2019;37:177–178.
   Google Scholar
• Ansell SM. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91:434–442.
   PubMed Web of Science ®Google Scholar
• Alinari L, Blum KA. How I treat relapsed classical Hodgkin lymphoma after autologous stem cell transplant. Blood. 2016;127:287–295.
   PubMed Web of Science ®Google Scholar
• Armand P, Chen Y-B, Redd RA, et al. PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation. Blood. 2018;132:1650.
   Web of Science ®Google Scholar
• Guolo F, Minetto P, Ballerini F, et al. Feasibility and efficacy of post-transplant consolidation immunotherapy with nivolumab supported by the reinfusion of unselected autologous lymphocytes in patients affected by relapsed/refractory Hodgkin lymphoma. Blood. 2018;132:4598.
   Web of Science ®Google Scholar
• Eichenauer DA, Aleman BMP, André M, et al. Hodgkin lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2018;29:iv19–iv29.
   PubMed Web of Science ®Google Scholar
• Spina F, Radice T, De Philippis C, et al. Allogeneic transplantation for relapsed and refractory Hodgkin lymphoma: long-term outcomes and graft-versus-host disease-free/relapse-free survival. Leuk Lymphoma. 2019;60:101–109.
   PubMed Web of Science ®Google Scholar
• Manson G, Mear J-B, Herbaux C, et al. Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation. Eur J Cancer Oxf Engl. 1990;2019(115):47–56.
   Google Scholar
• Davids MS, Kim HT, Costello CL, et al. A phase I/Ib study of nivolumab for relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation (alloHCT). Blood. 2018;132:705.
   Google Scholar
• Wong E, Dawson E, Davis J, et al. Nivolumab for relapsed or residual haematological malignancies after allogeneic haematopoietic stem cell transplantation (NIVALLO). Blood. 2018;132:4633.
   Web of Science ®Google Scholar
• Khan AY, Ijaz A, Usman M, et al. The use of checkpoint inhibitors before and after allogeneic stem cell transplantion: a double-edged sword. Blood. 2018;132:5722.
   Web of Science ®Google Scholar
• Lim SH, Johnson PWM. Optimizing therapy in advanced-stage Hodgkin lymphoma. Blood. 2018;131:1679–1688.
   PubMed Web of Science ®Google Scholar
• Ramchandren R, Domingo-Domènech E, Rueda A, et al. Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma: safety and efficacy in the phase II CheckMate 205 study. J Clin Oncol. 2019;37:1997–2007.
   PubMed Web of Science ®Google Scholar
• Domingo-Domenech E, Ramchandren R, Rueda A, et al. Nivolumab plus doxorubicin, vinblastine and dacarbazine for newly diagnosed advanced-stage classical Hodgkin lymphoma: 2-year extended follow-up from cohort D of the phase 2 CheckMate 205 study [Internet]. EHA Library. 2019 [cited 2019 Aug 26]. Available from: https://library.ehaweb.org/eha/2019/24th/267404/eva.domingo-domnech.nivolumab.plus.doxorubicin.vinblastine.and.dacarbazine.for.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D1550%2Aot_id%3D20976%2Amarker%3D530%2Afeatured%3D16435
   Google Scholar
• Allen PB, Evens AM, Pro B, et al. P105 (0032) a phase II study of pembrolizumab (PEM) followed by AVD for frontline treatment of classicaL Hodgkin Lymphoma (CHL): interim results. HemaSphere. 2018;2:42.
   Google Scholar
• Shi M, Roemer MGM, Chapuy B, et al. Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol. 2014;38:1715–1723.
   PubMed Web of Science ®Google Scholar
• Twa DDW, Chan FC, Ben-Neriah S, et al. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood. 2014;123:2062–2065.
   PubMed Web of Science ®Google Scholar
• Chapuy B, Roemer MGM, Stewart C, et al. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood. 2016;127:869–881.
   PubMed Web of Science ®Google Scholar
• Moskowitz AJ, Santoro A, Gritti G, et al. Nivolumab combined with brentuximab vedotin for relapsed/refractory primary mediastinal large B-cell lymphoma: preliminary results from the phase 2 CheckMate 436 trial. Blood. 2018;132:1691.
   Web of Science ®Google Scholar
• Zinzani PL, Santoro A, Gritti G, et al. Nivolumab combined with brentuximab vedotin for relapsed/refractory primary mediastinal large B-cell lymphoma: efficacy and safety from the phase II CheckMate 436 study. J Clin Oncol. 2019;19:01492, JCO
   Google Scholar
• Hamed R, Alshemmari S, Hamadah A, et al. Promising effect of PDL1 inhibitors in PCNSL. Blood. 2018;132:5392.
   Web of Science ®Google Scholar
• Yakimovich KP, Mikhailova NB, Lepik KV, et al. Nivolumab in B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma [Internet]. EHA Libr. 2019 [cited 2019 Aug 31. Available from: https://library.ehaweb.org/eha/2019/24th/267815/ksenia.yakimovich.nivolumab.in.b-cell.lymphoma.unclassifiable.with.features.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dnivolumab
   Google Scholar
• Shmidt D, Gavrilenko A, Polushin A, et al. Nivolumab treatment for relapsed and refractory primary central nervous system lymphoma and primary testicular lymphoma with CNS involvement [Internet]. EHA Libr. 2019 [cited 2019 Sep 15]. Available from: https://library.ehaweb.org/eha/2019/24th/267808/daniil.shmidt.nivolumab.treatment.for.relapsed.and.refractory.primary.central.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dnivolumab+central+nervous
   Google Scholar
• Nayak L, Iwamoto FM, LaCasce A, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017;129:3071–3073. blood-2017-01-764209
   PubMed Web of Science ®Google Scholar
• Armand P, Welch S, Kim HT, et al. Prognostic factors for patients with diffuse large B cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation in the positron emission tomography era. Br J Haematol. 2013;160:608–617.
   PubMed Web of Science ®Google Scholar
• Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:4199–4206.
   PubMed Web of Science ®Google Scholar
• Nowakowski GS, Willenbacher W, Greil R, et al. Safety and efficacy of PD-L1 inhibitor durvalumab with R-CHOP or R2-CHOP in subjects with previously untreated, high-risk DLBCL. J Clin Oncol. 2019;37:7520.
   Web of Science ®Google Scholar
• Elbæk MV, MØ P, Breinholt MF, et al. PD-L1 expression is low in large B-cell lymphoma with MYC or double-hit translocation. Blood. 2018;132:4113.
   Web of Science ®Google Scholar
• Smith SD, Lynch RC, Till BG, et al. Pembrolizumab with Rchop in previously untreated diffuse large B-cell and grade 3b follicular lymphoma: final results of a phase I trial. Hematol Oncol. 2019;37:120–121.
   Google Scholar
• Gravelle P, Burroni B, Péricart S, et al. Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies. Oncotarget. 2017;8:44960–44975.
   PubMedGoogle Scholar
• Andorsky DJ, Yamada RE, Said J, et al. Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17:4232–4244.
   PubMed Web of Science ®Google Scholar
• Carreras J, Lopez-Guillermo A, Roncador G, et al. High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytes are associated with improved overall survival in follicular lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27:1470–1476.
   PubMed Web of Science ®Google Scholar
• Richendollar BG, Pohlman B, Elson P, et al. Follicular programmed death 1-positive lymphocytes in the tumor microenvironment are an independent prognostic factor in follicular lymphoma. Hum Pathol. 2011;42:552–557.
   PubMed Web of Science ®Google Scholar
• Yang -Z-Z, Grote DM, Ziesmer SC, et al. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J. 2015;5:e281.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Westin JR, Chu F, Zhang M, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol. 2014;15:69–77.
   PubMed Web of Science ®Google Scholar
• Nastoupil L, Westin JR, Fowler NH, et al. High complete response rates with pembrolizumab in combination with rituximab in patients with relapsed follicular lymphoma: results of an open-label, phase II study. Blood. 2017;130:414.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Younes A, John BM, Diefenbach CS, et al. Safety and efficacy of atezolizumab in combination with obinutuzumab and bendamustine in patients with previously untreated follicular lymphoma: an interim analysis. Blood. 2017;130:481.
   Web of Science ®Google Scholar
• Miyoshi H, Kiyasu J, Kato T, et al. PD-L1 expression on neoplastic or stromal cell is respectively poor or good prognostic factor for adult T-cell leukemia/lymphoma. Blood. 2016;128:1374–1381, blood-2016-02-698936
   PubMed Web of Science ®Google Scholar
• Khodadoust MS, Rook AHPorcu P, et al. Pembrolizumab in relapsed and refractory mycosis fungoides and sézary syndrome: a multicenter phase ii study. J. Clin. Oncol. 2020;38:20–28.
   PubMed Web of Science ®Google Scholar
• Barta SK, Zain J, MacFarlane AW, et al. Phase II study of the PD-1 inhibitor pembrolizumab for the treatment of relapsed or refractory mature T-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2019;19:356–364.e3.
   PubMed Web of Science ®Google Scholar
• Tao R, Fan L, Song Y, et al. Sintilimab for relapsed/refractory (R/R) extranodal NK/T cell lymphoma (ENKTL): a multicenter, single-arm, phase 2 trial (ORIENT-4) [Internet]. EHA Libr. 2019 [cited 2019 Sep 15]. Available from: https://library.ehaweb.org/eha/2019/24th/267453/l.fan.sintilimab.for.relapsed.refractory.28r.r29.extranodal.nk.t.cell.lymphoma.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dsintilimab
   Google Scholar
• Schuster SJ, Bishop MR, Tam CS, et al. Primary analysis of juliet: a global, pivotal, phase 2 trial of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma. Blood. 2017;130:577.
   Google Scholar
• Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–2544.
   PubMed Web of Science ®Google Scholar
• Chavez JC, Bachmeier C, Kharfan-Dabaja MA. CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Ther Adv Hematol [Internet]. 2019 [cited 2019 Sep 15];10. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466472/
   PubMed Web of Science ®Google Scholar
• Locke FL, Westin JR, Miklos DB, et al. Phase 1 results from ZUMA-6: axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma (DLBCL). Blood. 2017;130:2826.
   Web of Science ®Google Scholar
• Hirayama AV, Gauthier J, Hay KA, et al. Efficacy and toxicity of JCAR014 in combination with durvalumab for the treatment of patients with relapsed/refractory aggressive B-cell non-hodgkin lymphoma. Blood. 2018;132:1680.
   Web of Science ®Google Scholar
• Chong EA, Svoboda J, Nasta SD, et al. Sequential anti-CD19 directed chimeric antigen receptor modified T-cell therapy (CART19) and PD-1 blockade with pembrolizumab in patients with relapsed or refractory B-cell non-hodgkin lymphomas. Blood. 2018;132:4198.
   Web of Science ®Google Scholar
• Beer L, Hochmair M, Prosch H. Pitfalls in the radiological response assessment of immunotherapy. Memo. 2018;11:138–143.
   PubMedGoogle Scholar
• Miller A, Asmann Y, Cattaneo L, et al. High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma. Blood Cancer J. 2017;7:e612.
   PubMed Web of Science ®Google Scholar
• Cao D, Xu H, Xu X, et al. High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients. Oncoimmunology. 2019;8:e1629258.
   PubMed Web of Science ®Google Scholar
• Voorwerk L, Slagter M, Horlings HM, et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019;25:920–928.
   PubMed Web of Science ®Google Scholar