Mitoxantrone, Vinblastine, and Lomustine (MVC): Long-Term Follow-Up of Patients Treated for Hodgkin’s Disease (HD).

Advanced-stage or relapsed/refractory HD has a poor prognosis despite aggressive chemotherapy regimens and the use of high dose therapy with autologous support. Sixty seven patients with HD(23 newly diagnosed and 45 with relapsed/refractory disease, one patient treated twice) were treated with the MVC regimen (mitoxantrone 8mg/m²/day IV days 1–3, vinblastine 8m/m²/day days 1 and 22, and CCNU 100 mg/m² on day 1, repeated at 6 to 8 wks) in a single-arm Phase II study. This regimen combines the most effective chemotherapeutic agents of previous regimens for poor prognosis HD, and eliminates marginally active agents with unnecessary toxicities. Median age at treatment was 35 years (16–71), with 42 males and 25 females. 23 patients had previously untreated (PU) disease, staged as II (7), III (7), IV (9), and subtypes consisted of nodular sclerosis (21), mixed cellularity (1), and lymphocyte depletion (1). 45 patients were previously treated (1^st relapse-20, 2^nd relapse-13, 3^rd relapse-12) and had relapsed after chemotherapy alone (17), radiotherapy alone (4), or combined modality treatment (24). 39 patients were relapsed and 6 refractory to treatment. This refractory/relapsed (R/R) group at diagnosis was staged II (11), III (10), IV (22), unknown (2), with 34 nodular sclerosis, 3 mixed cellularity, 1 anaplastic large cell, 1 lymphocyte predominant, 2 lymphocyte depleted, 4 unknown. All patients responded to treatment in the newly diagnosed group (OR 100%). The median response duration was 57.2 mos, and the median survival 108.1 mos. 11 complete responses are ongoing at 39+ to 189+ mos. In the prior treated patients, 41 responded to MVC (OR 91%). The median response duration for this group was 11 mos, and the median survival was 82.1 mos. Grade 3 and 4 treatment-related toxicities included neutropenia (89%), thrombocytopenia (73%), infection (40%), bleeding (20%), and two (2.9%) deaths (related to granulocytopenia and infection). Three secondary myeloid leukemias occurred, two in the de-novo, and one in the relapsed/refractory group, at a median follow-up of 16 years. In conclusion, MVC regimen for HD is very active, for both de novo and relapsed/refractory disease, with high response rates and survival that compare favorably with the results obtained by high-dose therapy with stem-cell transplantation. Although significant, the toxicities associated with this regimen were manageable.