Background: Standard treatment for relapsed/refractory classic Hodgkin lymphoma (HL) is second-line chemotherapy consolidated by high-dose therapy (HDT) with autologous stem cell transplant (ASCT); however, low-risk relapses may be salvaged effectively with conventional systemic therapy and radiation therapy (RT), without HDT/ASCT.
Methods: The prospective Children’s Oncology Group AHOD0431 trial explored low-intensity first- and second-line treatment of stage IA/IIA, non-bulky HL. We report outcomes for patients on AHOD0431 who experienced protocol-defined low-risk relapses. We focus on those who received reduced-intensity salvage therapy on study that consisted of 2 cycles of ifosfamide/vinorelbine, 2 cycles of dexamethasone/etoposide/cisplatin/cytarabine, and involved-field RT (21 Gy). 2nd event-free survival (EFS) was defined as the time from the first relapse to second relapse, second cancer, or death. Overall survival (OS) was defined as the time from the first relapse to death.
Results: Of 278 patients who received first-line therapy on AHOD0431, 32 experienced low-risk relapses and 20 completed protocol-specified reduced-intensity salvage therapy. Among all 32 patients with low-risk relapses, the median follow-up time was 9.1 years, and 8 second relapses occurred at a median of 1.8 years after the first relapse (range 0.2-9.2 years). 8-year 2nd EFS was 76.3% (95% CI, 56.3-88.0%) and OS was 100%. Five patients (15.6%) received HDT/ASCT following a second relapse. No second cancers occurred. Among the 20 patients who received reduced-intensity second-line therapy on protocol, 5 second relapses occurred at a median of 2.1 years after the first relapse (range 1.0-9.2 years). 8-year 2nd EFS was 78.5% (95%, CI 51.8%-91.4%) and OS was 100%. Three patients (15%) received HDT/ASCT following a second relapse.
Conclusions: In this cohort of patients with early-stage, favorable HL treated with minimal upfront chemotherapy, low-risk relapses were effectively salvaged using conventional chemotherapy and IFRT. 84% of patients avoided HDCT/ASCT, and OS was not compromised. These data support a role for transplant-free salvage of low-risk relapsed HL treated with modest upfront chemotherapy.
Bradford S. Hoppe, Sarah Milgrom, Lindsay A. Renfro, Yue Wu, Cindy Schwartz, Louis Constine, David Hodgson, Kathleen McCarten, Kara M. Kelly, Frank G. Keller, Sharon M. Castellino