Annals of Hematology

, Volume 96, Issue 4, pp 647–651 | Cite as

Low-dose pembrolizumab for relapsed/refractory Hodgkin lymphoma: high efficacy with minimal toxicity

  • Thomas S. Y. Chan
  • Tsan-Hei Luk
  • June S. M. Lau
  • Pek-Lan Khong
  • Yok-Lam Kwong
Original Article


Five patients with refractory/relapsed classical Hodgkin lymphoma (cHL), four having failed multiple lines of chemotherapy and brentuximab vedotin, were treated with low-dose pembrolizumab (median dose 100 mg, range: 100–200 mg, every 3 weeks). Complete response (CR) was achieved in four patients (80%), after a median cumulative dose of merely 495 (300–800) milligrams. Three CR patients have continued to receive pembrolizumab for a median of 16 (14–25) cycles, remaining in CR for a median of 18 (9–18) months. One CR patient underwent autologous hematopoietic stem cell transplantation and has remained in CR for 9 months. Partial response (PR) was achieved in one patient (20%), after a cumulative dose of 400 mg. The overall response rate was therefore 100% (CR: 80%; PR: 20%). Toxicity was virtually absent, with only grade 1 diarrhea and eczema each observed in one patient. Low-dose pembrolizumab was highly efficacious, achieving responses with minimal toxicity and at much lower costs.


Pembrolizumab Hodgkin lymphoma Relapse Refractory 



The authors have no acknowledgement to make.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Nguyen LT, Ohashi PS (2015) Clinical blockade of PD1 and LAG3-potential mechanisms of action. Nat Rev Immunol 15(1):45–56CrossRefPubMedGoogle Scholar
  2. 2.
    Villasboas JC, Ansell S (2016) Checkpoint inhibition: programmed cell death 1 and programmed cell death 1 ligand inhibitors in Hodgkin lymphoma. Cancer J 22(1):17–22CrossRefPubMedGoogle Scholar
  3. 3.
    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):311–319CrossRefPubMedGoogle Scholar
  4. 4.
    Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, Drengler R, Chen C, Smith L, Espino G, Gergich K, Delgado L, Daud A, Lindia JA, Li XN, Pierce RH, Yearley JH, Wu D, Laterza O, Lehnert M, Iannone R, Tolcher AW (2015) Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res 21(19):4286–4293CrossRefPubMedGoogle Scholar
  5. 5.
    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 Jun 27Google Scholar
  6. 6.
    Chen RW, Zinzani PL, Fanale MA, Armand P, Johnson N, Ribrag V, Radford JA, Tomita A, Shipp MA, Wang Y, Ricart AD, Balakumaran A, Moskowitz CH (2016). Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study. J Clin Oncol 34 (suppl; abstr 7555)Google Scholar
  7. 7.
    Kwong YL, Lopes D, Khong PL (2016). Low-dose pembrolizumab induced remission in patients with refractory classical Hodgkin lymphoma. Br J Haematol Jan 15Google Scholar
  8. 8.
    Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA, Alliance, Australasian Leukaemia and Lymphoma Group.; Eastern Cooperative Oncology Group.; European Mantle Cell Lymphoma Consortium.; Italian Lymphoma Foundation.; European Organisation for Research.; Treatment of Cancer/Dutch Hemato-Oncology Group.; Grupo Español de Médula Ósea.; German High-Grade Lymphoma Study Group.; German Hodgkin's Study Group.; Japanese Lymphoma Study Group.; Lymphoma Study Association.; NCIC Clinical Trials Group.; Nordic Lymphoma Study Group.; Southwest Oncology Group.; United Kingdom National Cancer Research Institute (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32(27):3059–3068CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hubscher SG, Lumley MA, Elias E (1993) Vanishing bile duct syndrome: a possible mechanism for intrahepatic cholestasis in Hodgkin's lymphoma. Hepatology 17(1):70–77CrossRefPubMedGoogle Scholar
  10. 10.
    Sathyanarayanan V, Foo WC, Fanale M, Westin J (2016) Deeper insights into vanishing bile duct syndrome in lymphoma: a perplexing entity. Clin Lymphoma Myeloma Leuk 16(5):e65–e70CrossRefPubMedGoogle Scholar
  11. 11.
    Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, KEYNOTE-001 Investigators (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 21;372(21):2018–2028CrossRefGoogle Scholar
  12. 12.
    Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, Schachter J, Pavlick AC, Lewis KD, Cranmer LD, Blank CU, O'Day SJ, Ascierto PA, Salama AK, Margolin KA, Loquai C, Eigentler TK, Gangadhar TC, Carlino MS, Agarwala SS, Moschos SJ, Sosman JA, Goldinger SM, Shapira-Frommer R, Gonzalez R, Kirkwood JM, Wolchok JD, Eggermont A, Li XN, Zhou W, Zernhelt AM, Lis J, Ebbinghaus S, Kang SP, Daud A (2015) Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol 16(8):908–918CrossRefPubMedGoogle Scholar
  13. 13.
    Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387(10027):1540–1550CrossRefPubMedGoogle Scholar
  14. 14.
    Chatterjee M, Turner DC, Felip E, Lena H, Cappuzzo F, Horn L, Garon EB, Hui R, Arkenau HT, Gubens MA, Hellmann MD, Dong D, Li C, Mayawala K, Freshwater T, Ahamadi M, Stone J, Lubiniecki GM, Zhang J, Im E, De Alwis DP, Kondic AG, Fløtten Ø (2016) Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Ann Oncol 27(7):1291–1298CrossRefPubMedGoogle Scholar
  15. 15.
  16. 16.
  17. 17.
    Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ (2007) Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27(1):111–122CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Chen L, Flies DB (2013) Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 13(4):227–242CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, Connelly CF, Sun HH, Daadi SE, Freeman GJ, Armand P, Chapuy B, de Jong D, Hoppe RT, Neuberg DS, Rodig SJ, Shipp MA (2016) PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol 34(23):2690–2697CrossRefPubMedGoogle Scholar
  20. 20.
    Scott DW, Gascoyne RD (2014) The tumour microenvironment in B cell lymphomas. Nat Rev Cancer 14(8):517–534CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Thomas S. Y. Chan
    • 1
  • Tsan-Hei Luk
    • 2
  • June S. M. Lau
    • 2
  • Pek-Lan Khong
    • 3
  • Yok-Lam Kwong
    • 1
  1. 1.Department of Medicine, Professorial BlockQueen Mary HospitalHong KongChina
  2. 2.Department of MedicineQueen Elizabeth HospitalHong KongChina
  3. 3.Department of Diagnostic RadiologyQueen Mary HospitalHong KongChina

Personalised recommendations