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Erschienen in: Strahlentherapie und Onkologie 2/2017

04.10.2016 | Editorial

Checkpoint inhibitors and radiation treatment in Hodgkin’s lymphoma

New study concepts of the German Hodgkin Study Group

verfasst von: C. Baues, R. Semrau, U. S. Gaipl, P. J. Bröckelmann, J. Rosenbrock, A. Engert, S. Marnitz

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 2/2017

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Abstract

Background

Patients with classical Hodgkin’s lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients.

Methods

Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin’s lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts.

Results

Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials.

Conclusion

The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.
Literatur
1.
Zurück zum Zitat Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465CrossRefPubMedPubMedCentral Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Keir ME, Butte MJ, Freeman GJ et al (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704CrossRefPubMed Keir ME, Butte MJ, Freeman GJ et al (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704CrossRefPubMed
3.
Zurück zum Zitat Green MR, Monti S, Rodig SJ et al (2010) Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B‑cell lymphoma. Blood 116:3268–3277CrossRefPubMedPubMedCentral Green MR, Monti S, Rodig SJ et al (2010) Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B‑cell lymphoma. Blood 116:3268–3277CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Ansell SM, Lesokhin AM, Borrello I et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319CrossRefPubMed Ansell SM, Lesokhin AM, Borrello I et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319CrossRefPubMed
5.
Zurück zum Zitat Yared JA, Hardy N, Singh Z et al (2016) Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant 51:850–852CrossRefPubMed Yared JA, Hardy N, Singh Z et al (2016) Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant 51:850–852CrossRefPubMed
6.
Zurück zum Zitat Derer A, Frey B, Fietkau R et al (2015) Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother 65:779. doi:10.1007/s00262-015- 1771-8 CrossRefPubMed Derer A, Frey B, Fietkau R et al (2015) Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother 65:779. doi:10.​1007/​s00262-015- 1771-8 CrossRefPubMed
7.
Zurück zum Zitat Eich HT, Kriz J, Schmidberger H et al (2013) The German evidence-based guidelines for Hodgkin’s lymphoma. Aspects for radiation oncologists. Strahlenther Onkol 189:445–447CrossRefPubMed Eich HT, Kriz J, Schmidberger H et al (2013) The German evidence-based guidelines for Hodgkin’s lymphoma. Aspects for radiation oncologists. Strahlenther Onkol 189:445–447CrossRefPubMed
8.
Zurück zum Zitat Gaipl US, Multhoff G, Scheithauer H et al (2014) Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy 6:597–610CrossRefPubMed Gaipl US, Multhoff G, Scheithauer H et al (2014) Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy 6:597–610CrossRefPubMed
9.
Zurück zum Zitat Multhoff G, Gaipl US, Niedermann G (2012) The role of radiotherapy in the induction of antitumor immune responses. Strahlenther Onkol 188(Suppl):312–315CrossRefPubMed Multhoff G, Gaipl US, Niedermann G (2012) The role of radiotherapy in the induction of antitumor immune responses. Strahlenther Onkol 188(Suppl):312–315CrossRefPubMed
10.
Zurück zum Zitat Barker CA, Postow MA (2014) Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int J Radiat Oncol Biol Phys 88:986–997CrossRefPubMedPubMedCentral Barker CA, Postow MA (2014) Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int J Radiat Oncol Biol Phys 88:986–997CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Stamell EF, Wolchok JD, Gnjatic S et al (2013) The abscopal effect associated with a systemic anti-melanoma immune response. Int J Radiat Oncol Biol Phys 85:293–295CrossRefPubMed Stamell EF, Wolchok JD, Gnjatic S et al (2013) The abscopal effect associated with a systemic anti-melanoma immune response. Int J Radiat Oncol Biol Phys 85:293–295CrossRefPubMed
12.
Zurück zum Zitat Sharabi AB, Nirschl CJ, Kochel CM et al (2015) Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res 3:345–355CrossRefPubMed Sharabi AB, Nirschl CJ, Kochel CM et al (2015) Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res 3:345–355CrossRefPubMed
13.
Zurück zum Zitat Troost EG (2016) Stereotactic radiotherapy augments the immune response. Strahlenther Onkol 192:70–71CrossRefPubMed Troost EG (2016) Stereotactic radiotherapy augments the immune response. Strahlenther Onkol 192:70–71CrossRefPubMed
14.
Zurück zum Zitat Deng L, Liang H, Burnette B et al (2014) Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 124:687–695CrossRefPubMedPubMedCentral Deng L, Liang H, Burnette B et al (2014) Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 124:687–695CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Behringer K, Goergen H, Hitz F et al (2015) Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet 385:1418–1427CrossRefPubMed Behringer K, Goergen H, Hitz F et al (2015) Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet 385:1418–1427CrossRefPubMed
16.
Zurück zum Zitat Engert A, Plutschow A, Eich HT et al (2010) Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 363:640–652CrossRefPubMed Engert A, Plutschow A, Eich HT et al (2010) Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 363:640–652CrossRefPubMed
17.
Zurück zum Zitat Kriz J, Spickermann M, Lehrich P et al (2015) Breath-hold technique in conventional APPA or intensity-modulated radiotherapy for Hodgkin’s lymphoma: Comparison of ILROG IS-RT and the GHSG IF-RT. Strahlenther Onkol 191:717–725CrossRefPubMed Kriz J, Spickermann M, Lehrich P et al (2015) Breath-hold technique in conventional APPA or intensity-modulated radiotherapy for Hodgkin’s lymphoma: Comparison of ILROG IS-RT and the GHSG IF-RT. Strahlenther Onkol 191:717–725CrossRefPubMed
18.
Zurück zum Zitat Hjermstad MJ, Oldervoll L, Fossa SD et al (2006) Quality of life in long-term Hodgkin’s disease survivors with chronic fatigue. Eur J Cancer 42:327–333CrossRefPubMed Hjermstad MJ, Oldervoll L, Fossa SD et al (2006) Quality of life in long-term Hodgkin’s disease survivors with chronic fatigue. Eur J Cancer 42:327–333CrossRefPubMed
19.
Zurück zum Zitat Daniels LA, Oerlemans S, Krol AD et al (2013) Persisting fatigue in Hodgkin lymphoma survivors: a systematic review. Ann Hematol 92:1023–1032CrossRefPubMed Daniels LA, Oerlemans S, Krol AD et al (2013) Persisting fatigue in Hodgkin lymphoma survivors: a systematic review. Ann Hematol 92:1023–1032CrossRefPubMed
20.
Zurück zum Zitat Raemaekers JM, Andre MP, Federico M et al (2014) Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 32:1188–1194CrossRefPubMed Raemaekers JM, Andre MP, Federico M et al (2014) Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 32:1188–1194CrossRefPubMed
21.
Zurück zum Zitat Kriz J, Baues C, Engenhardt-Cabillic R, et al: New Quality Assurance Program Integrating “Modern Radiotherapy” within the German Hodgkin Study Group (GHSG). Strahlenther Onkol: in press Kriz J, Baues C, Engenhardt-Cabillic R, et al: New Quality Assurance Program Integrating “Modern Radiotherapy” within the German Hodgkin Study Group (GHSG). Strahlenther Onkol: in press
22.
Zurück zum Zitat Kriz J, Baues C, Engenhardt-Carbillic R, et al: Report of the Radiotherapy Panel of the German Hodgkin Study Group (GHSG): Quality Control of Involved Field Radiotherapy within the HD 13 and HD 14 trials. Strahlenther Onkol: in press Kriz J, Baues C, Engenhardt-Carbillic R, et al: Report of the Radiotherapy Panel of the German Hodgkin Study Group (GHSG): Quality Control of Involved Field Radiotherapy within the HD 13 and HD 14 trials. Strahlenther Onkol: in press
23.
Zurück zum Zitat Krebs L, Amorin S, Brice P et al: Analyses of patterns-of-failure and prognostic factors according to radiation fields in early-stage Hodgkin lymphoma. Strahlenther Onkol: in press Krebs L, Amorin S, Brice P et al: Analyses of patterns-of-failure and prognostic factors according to radiation fields in early-stage Hodgkin lymphoma. Strahlenther Onkol: in press
Metadaten
Titel
Checkpoint inhibitors and radiation treatment in Hodgkin’s lymphoma
New study concepts of the German Hodgkin Study Group
verfasst von
C. Baues
R. Semrau
U. S. Gaipl
P. J. Bröckelmann
J. Rosenbrock
A. Engert
S. Marnitz
Publikationsdatum
04.10.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 2/2017
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-016-1050-4

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