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Adult Hodgkin Lymphoma Treatment (PDQ®)

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Last Modified: 02/28/2014

Recurrent Adult Hodgkin Lymphoma

Current Clinical Trials

Patients who experience a relapse after initial wide-field, high-dose radiation therapy have a good prognosis. Combination chemotherapy results in 10-year disease-free survival (DFS) and overall survival (OS) rates of 57% to 81% and 57% to 89%, respectively.[1-4] For patients who experience a relapse after initial combination chemotherapy, prognosis is determined more by the duration of the first remission than by the specific induction or salvage combination chemotherapy regimen. Patients whose initial remission after chemotherapy was longer than 1 year (late relapse) have long-term survival with salvage chemotherapy of 22% to 71%.[4-9] Patients whose initial remission after chemotherapy was shorter than 1 year (early relapse) do much worse and have long-term survival of 11% to 46%.[4,8,10]

Patients who relapse after initial combination chemotherapy usually undergo reinduction with the same or another chemotherapy regimen followed by high-dose chemotherapy and autologous bone marrow or peripheral stem cell or allogeneic bone marrow rescue.[11-15] This therapy has resulted in a 3- to 4-year DFS rate of 27% to 48%. Patients who are responsive to reinduction chemotherapy may have a better prognosis.

Two randomized trials have compared aggressive conventional chemotherapy versus high-dose chemotherapy with autologous hematopoietic stem cell transplantation for relapsed chemosensitive Hodgkin lymphoma (HL). Both trials show improvement in freedom from treatment failure at 3 years for the transplantation arm (75% vs. 45% and 55% vs. 34%, respectively); but no difference was observed in OS.[16,17][Level of evidence: 1iiDii]

In two retrospective reviews of patients who underwent autologous bone marrow transplantation (ABMT) for relapsed or refractory disease, a comparison was made of those who received involved-field radiation therapy (IF-XRT) for residual masses after high-dose therapy versus no further treatment.[18,19] Those who received IF-XRT had improved progression-free survival. Normalization of 18F-fluorodeoxyglucose–positron emission tomography–computed tomography (FDG-PET-CT) scans after reinduction therapy predicted a much better outcome after stem cell transplantation, with an event-free survival rate of 80% versus 29% in one phase II trial.[20][Level of evidence: 3iiiDi] For patients at high risk of residual HL after stem cell transplant, a phase III study (the AETHERA trial [NCT01100502]) is evaluating the role of brentuximab vedotin.

The use of human leukocyte antigen-matched sibling marrow (allogeneic transplantation) results in a lower relapse rate, but the benefit may be offset by increased toxic effects.[13,21,22] Reduced-intensity conditioning for allogeneic stem cell transplantation is also under clinical evaluation.[23-27]

Phase II trials support responses in relapsing patients using brentuximab vedotin (anti-tubulin agent attached to a CD30-specific monoclonal antibody) [28,29] and for bendamustine.[30][Level of evidence: 3iiiDiv] For patients with recurrent disease after ABMT, weekly vinblastine therapy has provided palliation with minimal toxic effects.[31][Level of evidence: 3iiiDiv]

Because of CD30 expression on malignant Reed-Sternberg cells of HL, but limited expression on normal cells, CD30 is a target for therapy. Brentuximab vedotin is a chimeric antibody directed against CD30, which is linked to the microtubule-disrupting agent, monomethyl auristatin E.[28,32,33] Response rates around 75% are seen with complete remissions around 30% to 50% and median progression-free survival of 4 to 8 months.[28,32,33][Level of evidence: 3iiiDiv]

For the small subgroup of patients with only limited nodal recurrence following initial chemotherapy, radiation therapy with or without additional chemotherapy may provide long-term survival for about 50% of these highly selected patients.[34,35]

Patients who do not respond to induction chemotherapy (about 10%–20% of all presenting patients) have less than a 10% survival rate at 8 years.[8] For these patients, high-dose chemotherapy and autologous bone marrow or peripheral stem cell or allogeneic bone marrow rescue are under clinical evaluation.[13,14,36-42] These trials have resulted in a 3- to 5-year DFS rate of 17% to 48%.[11-14,41]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult Hodgkin lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Ng AK, Li S, Neuberg D, et al.: Comparison of MOPP versus ABVD as salvage therapy in patients who relapse after radiation therapy alone for Hodgkin's disease. Ann Oncol 15 (2): 270-5, 2004.  [PUBMED Abstract]

  2. Specht L, Horwich A, Ashley S: Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease. Int J Radiat Oncol Biol Phys 30 (4): 805-11, 1994.  [PUBMED Abstract]

  3. Horwich A, Specht L, Ashley S: Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone. Eur J Cancer 33 (6): 848-53, 1997.  [PUBMED Abstract]

  4. Josting A, Franklin J, May M, et al.: New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's lymphoma study group. J Clin Oncol 20 (1): 221-30, 2002.  [PUBMED Abstract]

  5. Harker WG, Kushlan P, Rosenberg SA: Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med 101 (4): 440-6, 1984.  [PUBMED Abstract]

  6. Tourani JM, Levy R, Colonna P, et al.: High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease. J Clin Oncol 10 (7): 1086-94, 1992.  [PUBMED Abstract]

  7. Canellos GP, Petroni GR, Barcos M, et al.: Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B. J Clin Oncol 13 (8): 2005-11, 1995.  [PUBMED Abstract]

  8. Bonfante V, Santoro A, Viviani S, et al.: Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD. J Clin Oncol 15 (2): 528-34, 1997.  [PUBMED Abstract]

  9. Garcia-Carbonero R, Paz-Ares L, Arcediano A, et al.: Favorable prognosis after late relapse of Hodgkin's disease. Cancer 83 (3): 560-5, 1998.  [PUBMED Abstract]

  10. Longo DL, Duffey PL, Young RC, et al.: Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure. J Clin Oncol 10 (2): 210-8, 1992.  [PUBMED Abstract]

  11. Nademanee A, O'Donnell MR, Snyder DS, et al.: High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors. Blood 85 (5): 1381-90, 1995.  [PUBMED Abstract]

  12. Horning SJ, Chao NJ, Negrin RS, et al.: High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. Blood 89 (3): 801-13, 1997.  [PUBMED Abstract]

  13. Akpek G, Ambinder RF, Piantadosi S, et al.: Long-term results of blood and marrow transplantation for Hodgkin's lymphoma. J Clin Oncol 19 (23): 4314-21, 2001.  [PUBMED Abstract]

  14. Tarella C, Cuttica A, Vitolo U, et al.: High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: a multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence. Cancer 97 (11): 2748-59, 2003.  [PUBMED Abstract]

  15. Holmberg L, Maloney DG: The role of autologous and allogeneic hematopoietic stem cell transplantation for Hodgkin lymphoma. J Natl Compr Canc Netw 9 (9): 1060-71, 2011.  [PUBMED Abstract]

  16. Linch DC, Winfield D, Goldstone AH, et al.: Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet 341 (8852): 1051-4, 1993.  [PUBMED Abstract]

  17. Schmitz N, Pfistner B, Sextro M, et al.: Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet 359 (9323): 2065-71, 2002.  [PUBMED Abstract]

  18. Mundt AJ, Sibley G, Williams S, et al.: Patterns of failure following high-dose chemotherapy and autologous bone marrow transplantation with involved field radiotherapy for relapsed/refractory Hodgkin's disease. Int J Radiat Oncol Biol Phys 33 (2): 261-70, 1995.  [PUBMED Abstract]

  19. Poen JC, Hoppe RT, Horning SJ: High-dose therapy and autologous bone marrow transplantation for relapsed/refractory Hodgkin's disease: the impact of involved field radiotherapy on patterns of failure and survival. Int J Radiat Oncol Biol Phys 36 (1): 3-12, 1996.  [PUBMED Abstract]

  20. Moskowitz CH, Matasar MJ, Zelenetz AD, et al.: Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood 119 (7): 1665-70, 2012.  [PUBMED Abstract]

  21. Milpied N, Fielding AK, Pearce RM, et al.: Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation. J Clin Oncol 14 (4): 1291-6, 1996.  [PUBMED Abstract]

  22. Gajewski JL, Phillips GL, Sobocinski KA, et al.: Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease. J Clin Oncol 14 (2): 572-8, 1996.  [PUBMED Abstract]

  23. Sureda A, Robinson S, Canals C, et al.: Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 26 (3): 455-62, 2008.  [PUBMED Abstract]

  24. Thomson KJ, Peggs KS, Smith P, et al.: Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation. Bone Marrow Transplant 41 (9): 765-70, 2008.  [PUBMED Abstract]

  25. Sarina B, Castagna L, Farina L, et al.: Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood 115 (18): 3671-7, 2010.  [PUBMED Abstract]

  26. Kuruvilla J, Pintilie M, Stewart D, et al.: Outcomes of reduced-intensity conditioning allo-SCT for Hodgkin's lymphoma: a national review by the Canadian Blood and Marrow Transplant Group. Bone Marrow Transplant 45 (7): 1253-5, 2010.  [PUBMED Abstract]

  27. Peggs KS, Kayani I, Edwards N, et al.: Donor lymphocyte infusions modulate relapse risk in mixed chimeras and induce durable salvage in relapsed patients after T-cell-depleted allogeneic transplantation for Hodgkin's lymphoma. J Clin Oncol 29 (8): 971-8, 2011.  [PUBMED Abstract]

  28. Younes A, Gopal AK, Smith SE, et al.: Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 30 (18): 2183-9, 2012.  [PUBMED Abstract]

  29. Chen R, Palmer JM, Thomas SH, et al.: Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma. Blood 119 (26): 6379-81, 2012.  [PUBMED Abstract]

  30. Moskowitz AJ, Hamlin PA Jr, Perales MA, et al.: Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 31 (4): 456-60, 2013.  [PUBMED Abstract]

  31. Little R, Wittes RE, Longo DL, et al.: Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. J Clin Oncol 16 (2): 584-8, 1998.  [PUBMED Abstract]

  32. Gopal AK, Ramchandren R, O'Connor OA, et al.: Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood 120 (3): 560-8, 2012.  [PUBMED Abstract]

  33. Younes A, Bartlett NL, Leonard JP, et al.: Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363 (19): 1812-21, 2010.  [PUBMED Abstract]

  34. Uematsu M, Tarbell NJ, Silver B, et al.: Wide-field radiation therapy with or without chemotherapy for patients with Hodgkin disease in relapse after initial combination chemotherapy. Cancer 72 (1): 207-12, 1993.  [PUBMED Abstract]

  35. Josting A, Nogová L, Franklin J, et al.: Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group. J Clin Oncol 23 (7): 1522-9, 2005.  [PUBMED Abstract]

  36. Marshall NA, DeVita VT Jr: Hodgkin's disease and transplantation: a room with a (nontransplanter's) view. Semin Oncol 26 (1): 67-73, 1999.  [PUBMED Abstract]

  37. Lazarus HM, Rowlings PA, Zhang MJ, et al.: Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 17 (2): 534-45, 1999.  [PUBMED Abstract]

  38. Fermé C, Mounier N, Diviné M, et al.: Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial. J Clin Oncol 20 (2): 467-75, 2002.  [PUBMED Abstract]

  39. Sweetenham JW, Carella AM, Taghipour G, et al.: High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin's disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party. J Clin Oncol 17 (10): 3101-9, 1999.  [PUBMED Abstract]

  40. Laurence AD, Goldstone AH: High-dose therapy with hematopoietic transplantation for Hodgkin's lymphoma. Semin Hematol 36 (3): 303-12, 1999.  [PUBMED Abstract]

  41. Gopal AK, Metcalfe TL, Gooley TA, et al.: High-dose therapy and autologous stem cell transplantation for chemoresistant Hodgkin lymphoma: the Seattle experience. Cancer 113 (6): 1344-50, 2008.  [PUBMED Abstract]

  42. Morschhauser F, Brice P, Fermé C, et al.: Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol 26 (36): 5980-7, 2008.  [PUBMED Abstract]