Abstract
Introduction: The combination of brentuximab vedotin (BV) with AVD chemotherapy followed by 30 Gy involved-site radiotherapy (ISRT) for the treatment of early stage, unfavorable risk Hodgkin lymphoma (HL) has demonstrated promising efficacy and an acceptable safety profile in the first cohort of this pilot study (Kumar et al., Blood, 2016). In cohort 2, we evaluated whether the reduced dose of ISRT to 20 Gy decreased RT-related toxicity while maintaining efficacy. Methods: Patients received 4 cycles of BV 1.2 mg/kg with AVD chemotherapy every 2 weeks followed by 30 Gy ISRT in cohort 1 and 20 Gy ISRT in cohort 2. Eligible patients had untreated stage I/II classical HL with any of the following unfavorable risk factors: bulky disease (maximal transverse or coronal diameter > 7 cm on CT), elevated ESR, extranodal involvement, >2 lymph node sites, or infradiaphragmatic disease. Patients with stage IIB disease with disease bulk or extranodal involvement were eligible. PET/CT after 2 and 4 cycles and ISRT were interpreted with the Deauville 5-point scale (negative = 1-3). The primary endpoint of cohort 2 was to evaluate preliminary efficacy by complete response (CR) rate. Results: In cohort 2, 29 patients were enrolled from May 2015 to October 2016 with median age of 33 (range, 19-55), 100% stage II, 69% with disease bulk (>7 cm), 38% elevated ESR, 38% B-symptoms, 21% extranodal involvement, 69% >2 involved lymph node sites, and 3% infradiaphragmatic disease. Twenty patients (69%) had bulky anterior mediastinal masses, ranging from 7 to 17.3 cm. Nine patients (31%) had advanced stage disease by the GHSG criteria: IIBX (n = 7) and IIBXE (n = 2). In cohort 2, 90% and 93% of patients achieved a negative PET scan after 2 and 4 cycles of therapy, respectively. Of the 2 patients with positive PET-4 scans, one underwent a biopsy that was negative for HL, and the other had residual FDG-uptake in a location not amenable to biopsy. Both patients received ISRT. The 25 patients who completed combined modality therapy (CMT) have achieved CRs. To date, the duration of remission ranges from 2 to 13 months, and no relapses have occurred. The efficacy is similar across cohorts 1 and 2 with interim PET negative rates of ≥90%, and all patients who completed CMT have achieved a CR (Figure 1). In cohort 1, 2 patients had biopsy-proven primary refractory HL after 4 cycles of chemotherapy, and in cohort 2, there have been no treatment failures. Conclusion: BV + AVD x 4 cycles followed by 20 Gy ISRT has promising preliminary efficacy for the treatment of early stage, unfavorable risk HL, including a high proportion of patients with bulky disease. As with 4 cycles of escalated BEACOPP tested in the GHSG HD11 clinical trial, 20 Gy ISRT may be adequate consolidation after BV + AVD x 4 cycles. We recommend that BV + AVD x 4 + 20 Gy ISRT is studied in a larger, randomized prospective study for early stage, bulky HL. Updated response data for all patients will be presented at the meeting. Keywords: brentuximab vedotin; Hodgkin lymphoma (HL)
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