ISHL10 Abstract T017

Phase III study of response adapted therapy for the treatment of children with newly diagnosed very high risk Hodgkin Lymphoma (Stages IIIB/IVB) (AHOD0831): a report from the Children’s Oncology Group

PURPOSE: AHOD0831 tested a response-based treatment approach for children with very high risk Hodgkin lymphoma (HL). Central review following 2 cycles by FDG-PET was used to assign consolidation chemotherapy and radiotherapy (RT). As many patients with relapsed HL can be successfully cured with retrieval therapy, 2ndEFS (freedom from 2nd relapse or malignancy) was used as a surrogate for long term HL-related cause of death. AHOD0831 tested whether this treatment would maintain 4yr 2ndEFS ≥95%. METHODS: Patients ≤21 with stage IIIB/IVB HL were nonrandomly assigned to receive two 21-day cycles of ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid Early Response (RER) was defined by FDG-PET without activity above background, irrespective of residual masses. RER received 2 additional cycles of ABVE-PC. Slow early responders (SER) received 2 cycles of ifosfamide/vinorelbine and 2 more ABVE-PC. Sites of initial bulky involvement (large mediastinal mass, nodal aggregate >6cm, splenic macronodules) and regions of SER received RT 21 Gy. 2nd events were defined as relapse/PD of HL or SMN, new SMN or death after a 1st event (relapse/PD, SMN, biopsy proven HL at end of chemotherapy). RESULTS: The 165 eligible patients were: median age 15.8 yrs (5.2-21.4), 61% male, 43% stage IIIB. 50% were RER. Median follow-up was 42 mos. 1st events: 29 relapse/PD, 1 SMN, 1 fungal death. 4yr 1stEFS rates 80.2% (73%-85.6%). 4yr OS 95.9% (90%-98.4%). 12 SER were persistently PET+ at end of chemotherapy; 8 had clinical evidence of active HL: 3 biopsy-proven HL, 2 PD by clinical or radiographic criteria, and 3 relapsed. 20 patients were excluded from 2ndEFS analysis due to premature termination or deviation of protocol therapy. 2ndEFS at 4yrs is 89.8% (95% CI:80.8%-94.8%). 4yr 2ndEFS was 91.9% (76.3%-97.4%) for RER, 87.8% (75.8%-94.1%) for SER (n=68) and 89.6% (76.3%-95.7%) for stage IVB. CONCLUSIONS: Among pediatric patients with VHR HL, a response directed approach with limited chemotherapy and risk-directed RT achieved EFS and OS rates comparable with results of recent trials for this population (POG 9425: IIIB/IVB, n=88: 4yr EFS 81.7%; 4 yr OS 92.9%) despite reduction in RT volumes. The similar EFS/2ndEFS for RER and SER supports therapeutic tailoring based on response. Persistent PET at end of chemotherapy identifies a cohort at especially high risk for relapse/early PD. Novel approaches are needed for this group.