Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

Abstract

The GHSG trial HD11 established 4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by involved field radiation therapy (IFRT) as the standard of care for patients with early unfavorable Hodgkin lymphoma (HL). Despite these results, practitioners often still recommend 6 cycles of chemotherapy followed by radiation therapy (RT), especially for patients with high risk features. We compared the outcomes of patients treated with 4 vs. 6 cycles of ABVD followed by RT, including patients with bulky disease. We also examined the relapse rates of patients treated with involved site radiation therapy (ISRT) compared with IFRT. One hundred twenty-eight patients diagnosed with early stage, unfavorable HL by GHSG criteria and treated between 2000 and 2013 were identified. Medical records were reviewed for clinical, pathologic, and treatment information as well as toxicities. Clinical outcomes including overall survival (OS) and freedom from relapse (FFR) were estimated for the entire cohort as well as a subset of bulky patients using the Kaplan-Meier method. One hundred twenty-eight patients were included in the study with a median follow-up of 5.0 years. Seventy patients (55%) received 4 cycles of chemotherapy and 58 patients (45%) received 6 cycles. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4 cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6 cycle group. 68% of all patients received ISRT. Six year OS was 100% and 97% for patients receiving 4 and 6 cycles of chemotherapy, respectively (P = 0.35). Six year FFR was 100% and 98% for patients receiving 4 and 6 cycles of chemotherapy, respectively (P = 0.28). A greater proportion of patients received 6 cycles of chemotherapy if treated before 2010 (year of HD11 report) (P = 0.01) and if bulky disease was present (P < 0.01). A greater proportion of patients developed bleomycin pulmonary toxicity in the group receiving 6 cycles of chemotherapy (20% vs 31%, P = 0.16). Six year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P = 0.58). Patients with bulky disease had a median follow up of 4.7 years. Amongst these patients, there were no significant differences in 4 year FFR between the 4 (100%) and 6 (98%) cycle group (P = 0.48). Four year FFR was 100% and 98% for patients receiving IFRT and ISRT, respectively (P = 0.52). There were no deaths in the patient group with bulky disease. Patients diagnosed with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by radiation therapy. Six cycles of chemotherapy does not appear superior in terms of disease control and may provide little added value in this population, even for patients with high risk features such as bulky disease. Increased relapse rates are not seen with ISRT compared to IFRT after 4 cycles of ABVD.