Vinblastine, Mitoxantrone and Prednisone (MVP) Followed by Involved Field Radiotherapy (IF-XRT) for Early Clinical Stage Hodgkins’s Lymphoma: Long Term Follow-Up.

Background: The treatment of early stage Hodgkin’s lymphoma (HL) continues to evolve in attempt to improve the safety profile of the regimens and decrease their long-term toxicities. Treatment related mortality exceeds that from HL after 12 to 15 years. In light of the potential long-term complications associated with irradiation and chemotherapy, particularly pulmonary and cardiac toxicity, alternative approaches minimizing exposure to drugs with long-term organ toxicity have been examined. Objectives: We evaluated a novel regimen of MVP and IF-XRT for non-bulky early-stage HL. The primary outcomes were response rate and freedom from disease progression. Secondary outcomes were toxicity, specifically pulmonary and cardiac dysfunction. Methods: Patients were enrolled in this multi-site phase 2 study between 1995 and 1999. Eligible patients were 18 years of age or older, had ECOG performance status 0–2 and pathologically confirmed, clinically staged non-bulky Stage I or II HL. Patients received a minimum of four cycles of mitoxantrone 8mg/m2 and vinblastine 6 mg/m2 intravenously on days 1 and 15 of each 28-day cycle. Prednisone 100mg was given orally days 1 to 5 and 15 to 19. Chemotherapy was continued for two additional cycles after complete response, up to eight cycles. Patients then received IF-XRT (30.6 Gy-39.6 Gy) four weeks after completion of chemotherapy. G-CSF was not used as primary prophylaxis. Results: Thirty-four patients were evaluated for response in a final review. A total of 32 patients (94%) achieved a complete remission after combined therapy. Thirty patients (88%) achieved a complete response after chemotherapy alone. At a median follow-up of 49 months (range 16.9–79.7 months), 10 patients had relapsed, and three deaths were documented. None of the deaths occurred during treatment. The median time to progression was 30 months. The overall survival and disease-free survival rates at 5 years were 90% (95% confidence interval [CI], 73–97%) and 78% (95% CI, 58–89%), respectively. The treatment was well tolerated without significant grade 3/4 toxicity. (Grade 3/4 leukopenia 18% of patients; neutropenia 28%) There were no significant changes in DLCO or left ventricular ejection fraction at 12 months observed after chemotherapy. Twenty-one patients received only 4 cycles of chemotherapy; the median dose intensity for the entire group was 85%. Conclusions: As the management of early-stage HL continues to evolve in attempt to reduce long-term toxicity, this trial serves as a reminder of the balance required between efficacy and toxicity in this largely curable population. In this relatively well-tolerated regimen, there was minimal long-term toxicity, but a high number of relapses, most of which were successfully salvaged with resultant excellent 5-year overall survival rates. As the treatment for early-stage HL moves forward, there will undoubtedly be further attempts to modify the ABVD backbone. We await those results as well as long term data from the German Hodgkin Study group investigating reduction of combined modality treatment (HD10) in a similar patient population.