Metabolic-only response assessment for omission of residual node radiation therapy (RNRT) for patients with classical Hodgkin lymphoma (cHL) and impact on event free (EFS) and overall survival (OS): A report from the Pediatric Hodgkin Consortium’s phase 2 study cHOD17 (NCT03755804).

Abstract

10018 Background: The AEPA/CAPDac (brentuximab vedotin, etoposide, prednisone, doxorubicin [cumulative dose = 160mg/m 2 ], cyclophosphamide, brentuximab vedotin, prednisone, and dacarbazine) regimen results in excellent EFS and OS rates for pediatric cHL but resulted in 65% of patients requiring RNRT using metabolic and anatomic response criteria. We aimed to determine if use of a metabolic-only response assessment would allow omission of consolidative prednisone and RNRT for the majority of high-risk patients while maintaining a high EFS. Methods: cHOD17 is an open-label, single-arm, multicenter, phase 2 trial with a stratum for patients ≤25 yrs of age at diagnosis of high-risk (stage IIB, IIIB, or IV), CD30+ cHL. 18 FDG-PET only (rather than + anatomic) was used to guide therapy following 2 cycles of AEPA [adapted from the HLHR13 trial (NCT01920932), without mandated growth factor] at the early response assessment (ERA). Complete (CMR) and inadequate metabolic responses (IR) were defined as Deauville ≤3 and ≥4, respectively. Patients in overall CMR received 4 CADac cycles without prednisone or RNRT. IR patients received 4 CAPDac (with prednisone) followed by consolidative IR site directed RNRT (25.5 Gy). The primary objective was to estimate EFS utilizing this approach. Results: 114 patients were enrolled at 7 institutions from January 2019 to February 2024. Median (range) age at diagnosis was 16.4 (6.7-24.1) yrs and follow-up 2.5 (0.4-5.7) yrs. Most (79.8%) were nodular sclerosing histology. Stages included 22.8% IIB, 16.7% IIIB, 20.2% IVA, and 40.4% IVB. One patient discontinued therapy due to treatment-related toxicity and was unavailable for response assessment. Of 113 remaining, 69 (61.1%) achieved a CMR at ERA and were spared RNRT and glucocorticoids during the CAPDac cycles. The 2-yr EFS was 94.7% (95% CI: 90.3%-99.4%) and OS 100% (95% CI: 100%-100%). Five of six relapses ( < 3 mo (N = 1), 3-12 mo (N = 2), and > 12 mos (N = 3) following therapy) occurred in individuals with an IR. The most frequent grade ≥3 toxicities were lymphopenia (84.2%) and neutropenia (91.2%). Grade 3 and 4 febrile neutropenia occurred in 21.1% and 1%, respectively. Neuropathy grade ≥3 was not observed. Serious adverse events were rare (n = 4) and included: multi-organ failure during cycle 1 that recovered (n = 2), therapy-related myeloid leukemia in remission following allotransplant (n = 1), and infection-related death during allotransplant for relapse (n = 1). Conclusions: A metabolic-only response assessment in the AEPA-CAPDac regimen results in high rates of omission of consolidative RT and glucocorticoids while limiting cumulative anthracycline exposure and maintaining excellent 2-year EFS of 94.7% and OS of 100%. Clinical trial information: NCT03755804 .