B. S. Hoppe1, S. A. Milgrom2, L. Renfro3, Y. Wu4, C. Schwartz5, L. S. Constine6, K. M. McCarten7, K. M. Kelly8, S. Castellino9, and F. Keller9; 1Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 2University of Colorado, Department of Radiation Oncology, Aurora, CO, 3University of Southern California, Los Angeles, CA, 4University of Florida, Gainesville, FL, 5Division of Pediatric Hematology, Oncology and BMT, Medical College of Wisconsin, Milwaukee, WI, 6Department of Radiation Oncology and Pediatrics, University of Rochester Medical Center, Rochester, NY, 7Brown University, Providence, RI, 8Roswell Park Cancer Institute, Buffalo, NY, 9Children Hospital of Atlanta, Atlanta, GA
Purpose/Objective(s): 2nd line systemic therapy followed by high-dose therapy and stem cell transplant (HDT/SCT) is the standard of care treatment for pediatric patients with relapsed classic Hodgkin lymphoma (prHL). We investigated a reduced intensity 2nd line treatment with chemotherapy and involved field radiotherapy (IFRT) for patients with low-risk prHL on AHOD 0431. Materials/
Methods: AHOD 0431 was a prospective clinical study of pediatric patients with Stage IA/IIA, non-bulky classic Hodgkin lymphoma that investigated AVPC (doxorubicin, vincristine, prednisone, cyclophosphamide) x 3 cycles. Patients with a complete response (CR) following AVPC did not receive IFRT, while those with a partial response by CT or PET received 21 Gy IFRT. Embedded in the study was reduced-intensity 2nd line treatment for patients with a low-risk relapse, defined as patients who achieved a CR following AVPCx3, did not receive IFRT, and had stage IA or IIA disease relapse. These patients received IV/DECAx2 (vinorelbine, ifosfamide, dexamethasone, etoposide, cisplatin, cytarabine) followed by 21 Gy IFRT. 2nd event-free survival (EFS) was defined as the time from 1st relapse to 2nd relapse, 2nd cancer, or death, and overall survival (OS) was defined as the time from 1st relapse to death. Results: Among162 patients that achieved a CR to AVPC alone and did not receive IFRT, 37 patients experienced a relapse, including 5 high-risk and 32 low-risk relapses. For the 32 low-risk relapses: median age 14 (range 6-21), 56% female, 78% white, 88% non-hispanic/latino, and 44% stage IIA at relapse. 20 completed protocol-defined salvage (IV/DECA + IFRT) at COG sites. Reasons for not receiving this treatment included patient/family refusal (n=5), study closed at the time of relapse (n=2), no biopsy confirmation (n=2), incorrectly staged bulky disease (n=1), unknown (n=1), RT completed at non-COG site (n=1). Among the 32 patients with low-risk relapse, 8 patients developed a 2nd relapse of which 5 received HDT/SCT. The 2yr and 5yr 2nd EFS were 84% (95% CI, 65.8%-93.0%) and 80.5% (95% CI, 61.6%- 90.8%). The 10 yr OS was 100% and no 2nd cancers occurred. Restricted to the 20 patients who completed protocol treatment, 85% achieved a CR, 5% had stable disease, and 10% had no evaluation. Five experienced a 2nd relapse and 3 received HDT/SCT. The 2yr and 5 yr 2nd EFS were 90% (95% CI, 65.6%-97.4%) and 85% (95% CI, 60.4%-94.9%). Conclusion: Among pediatric patients with low-risk relapse HL, 2nd line treatment with chemotherapy followed by IFRT alone was safe and effective with outstanding overall survival and only 16% going on to receive HDT/SCT. Further studies are needed to explore transplant-free regimens for patients with low-risk relapsed Hodgkin Lymphoma.