Advanced Favorable Hodgkin Lymphoma
Drug combinations described in this section include the following:
- ABVD: doxorubicin, bleomycin, vinblastine, and dacarbazine.
- CEC: cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin.
- MOPP: mechlorethamine, vincristine, procarbazine, and prednisone.
- MOPP/ABV hybrid: mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, and vinblastine.
- Stanford V: doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, and prednisone.
- MOPPEBVCAD: mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine.
Patients are designated as having advanced favorable Hodgkin lymphoma (HL) if they have clinical stage III or stage IV disease and three or fewer risk factors on the International Prognostic Index for HL, which corresponds to a freedom-from-progression at greater than 80% at 5 years with combination chemotherapy.
ABVD therapy for 6 to 8 months is as effective as 12 months of MOPP alternating with ABVD, and both are superior to MOPP alone in terms of failure-free survival (FFS) (50% vs. 36% with a 14-year median follow-up; P = .03).[2,3][Level of evidence: 1iiA] The Intergroup trial comparing ABVD with MOPP/ABV hybrid showed equivalent efficacy in FFS and overall survival (OS), but increased toxic effects in the hybrid arm, especially from second malignancies.[Level of evidence: 1iiA]
A prospective, randomized study, from the Medical Research Council (MRC) (MRC-UKLG-LY09), of 807 patients compared ABVD with two multidrug regimens also incorporating etoposide, chlorambucil, vincristine, and procarbazine. With 52 months' median follow-up, the 3-year event-free survival was 75% (confidence interval [CI], 71%–79%) for all three regimens, and 88% to 90% OS (CI, 84%–93%) for all three regimens, but there were significantly fewer toxic effects with ABVD.[Level of evidence: 1iiA]
A prospective, randomized study of 331 patients compared ABVD with escalated BEACOPP, along with a planned autologous stem cell transplantation after reinduction chemotherapy for relapsed or resistant disease. With 61 months' median follow-up, although 7-year freedom from first progression favored escalated BEACOPP (73% vs. 85%, P = .004), 7-year OS was not statistically different (84% vs. 89%, P = .39).[Level of evidence: 1iiA] Escalated BEACOPP is associated with increased rates of myelodysplasia and acute myelogenous leukemia (3%–4%). Stanford V is an alternative drug combination with mandated radiation consolidation for most patients and survival rates comparable to those with ABVD.[8-10][Level of evidence: 1iiA]
A prospective, randomized trial of 307 patients with advanced-stage disease, including IIB disease and advanced-favorable Hodgkin lymphoma patients, compared ABVD, BEACOPP (four escalated courses plus two standard courses), and CEC. With a median follow-up of 41 months, although progression-free survival favored BEACOPP over ABVD (78% vs. 68%, P = .038), there was no significant difference in OS.[Level of evidence: 1iiDiii] Further follow-up is required to assess rates of secondary malignancies with these regimens.
In a meta-analysis of 1,740 patients treated on 14 different trials, no improvement was observed in 10-years' OS for patients with advanced-stage HL who received combined modality therapy versus chemotherapy alone.[Level of evidence: 1iiA] Three prospective, randomized trials and a meta-analysis did not show a benefit in OS from the addition of consolidative radiation therapy to chemotherapy for patients with advanced-stage disease.[13-16] The lack of difference in OS was attributed to a greater number of second malignancies and poorer response and survival after relapse among patients who received combined modality therapy.
Proposed clinical trials will explore consolidation for patients with positive positron emission tomography testing after four cycles of ABVD.
Treatment options include the following:
- ABVD for six to eight cycles.
- ABVD for six to eight cycles plus IF-XRT for some patients with bulky disease.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III adult Hodgkin lymphoma and stage IV 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
- Moccia AA, Donaldson J, Chhanabhai M, et al.: International Prognostic Score in advanced-stage Hodgkin's lymphoma: altered utility in the modern era. J Clin Oncol 30 (27): 3383-8, 2012. [PUBMED Abstract]
- Canellos GP, Anderson JR, Propert KJ, et al.: Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327 (21): 1478-84, 1992. [PUBMED Abstract]
- Canellos GP, Niedzwiecki D: Long-term follow-up of Hodgkin's disease trial. N Engl J Med 346 (18): 1417-8, 2002. [PUBMED Abstract]
- Duggan DB, Petroni GR, Johnson JL, et al.: Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol 21 (4): 607-14, 2003. [PUBMED Abstract]
- Johnson PW, Radford JA, Cullen MH, et al.: Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol 23 (36): 9208-18, 2005. [PUBMED Abstract]
- Viviani S, Zinzani PL, Rambaldi A, et al.: ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med 365 (3): 203-12, 2011. [PUBMED Abstract]
- Scholz M, Engert A, Franklin J, et al.: Impact of first- and second-line treatment for Hodgkin's lymphoma on the incidence of AML/MDS and NHL--experience of the German Hodgkin's Lymphoma Study Group analyzed by a parametric model of carcinogenesis. Ann Oncol 22 (3): 681-8, 2011. [PUBMED Abstract]
- Hoskin PJ, Lowry L, Horwich A, et al.: Randomized comparison of the stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol 27 (32): 5390-6, 2009. [PUBMED Abstract]
- Gobbi PG, Levis A, Chisesi T, et al.: ABVD versus modified stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. J Clin Oncol 23 (36): 9198-207, 2005. [PUBMED Abstract]
- Gordon LI, Hong F, Fisher RI, et al.: Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol 31 (6): 684-91, 2013. [PUBMED Abstract]
- Federico M, Luminari S, Iannitto E, et al.: ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 27 (5): 805-11, 2009. [PUBMED Abstract]
- Loeffler M, Brosteanu O, Hasenclever D, et al.: Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. J Clin Oncol 16 (3): 818-29, 1998. [PUBMED Abstract]
- Fabian CJ, Mansfield CM, Dahlberg S, et al.: Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study. Ann Intern Med 120 (11): 903-12, 1994. [PUBMED Abstract]
- Aleman BM, Raemaekers JM, Tirelli U, et al.: Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med 348 (24): 2396-406, 2003. [PUBMED Abstract]
- Fermé C, Mounier N, Casasnovas O, et al.: Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood 107 (12): 4636-42, 2006. [PUBMED Abstract]
- Franklin JG, Paus MD, Pluetschow A, et al.: Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk. Cochrane Database Syst Rev (4): CD003187, 2005. [PUBMED Abstract]