ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma

Abstract

Background: Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths.

Methods: We randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival.

Results: The median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin's lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkin's lymphoma or early toxic effects from the treatment and 20 were related to another cause.

Conclusions: Among patients with Hodgkin's lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.).

Figures

Figure 1. Kaplan–Meier Estimates of Overall Survival and Freedom from Disease Progression

A total of 405 patients with stage IA or IIA nonbulky Hodgkin’s lymphoma were randomly assigned to receive treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment that included sub-total nodal radiation therapy; 399 of the patients were included in the analyses. Among the 203 patients assigned to subtotal nodal radiation therapy, 64 had a favorable risk profile and received subtotal nodal radiation therapy alone and 139 had an unfavorable risk profile and received two cycles of ABVD plus subtotal nodal radiation therapy. At 12 years, the rate of overall survival (Panel A) was 94% among patients in the ABVD-only group and 87% among patients in the radiation-therapy group, and the rate of freedom from disease progression (Panel B) was 87% and 92% in the two groups, respectively.

Figure 2. Kaplan–Meier Estimates of Overall Survival and Freedom from Disease Progression among Patients with an Unfavorable Risk Profile

Patients with unfavorable clinical features were randomly assigned to receive ABVD alone or to receive combination treatment with two cycles of ABVD plus subtotal nodal radiation therapy. At 12 years, the rate of overall survival (Panel A) was 92% among patients who received ABVD alone as compared with 81% among those who received combination treatment, and the rate of freedom from disease progression (Panel B) was 86% and 94% in the two groups, respectively.