Joanna C. Yang1, Anita Kumar1, Carla Casulo2, Ranjana Advani3, Elizabeth Budde4, Paul M. Barr2, Connie L. Batlevi1, Philip Caron1, Robert Chen4, Louis S. Constine2, Amanda Courtien1, Savita V. Dandapani4, Pamela Drullinsky1, Jonathan W. Friedberg2, Audrey Hamilton1, Paul A. Hamlin1, Richard T. Hoppe3, Steven M. Horwitz1, Andrew Intlekofer1, Oscar Lahoud1, Matthew J. Matasar1, Alison J. Moskowitz1, Ariela Noy1, Maria L. Palomba1, Carol S. Portlock1, Heiko Schöder1, David J. Straus1, Santosh Vardhana1, Shreya Vemuri1, Anas Younes1, Andrew D. Zelenetz1, Zhigang Zhang1, Joachim Yahalom1, and Craig H. Moskowitz5
1 Memorial Sloan Kettering Cancer Center, NY, NY, 2 Wilmot Cancer Institute, University of Rochester, Rochester, NY, 3 Stanford Cancer Institute, Stanford University, Stanford, CA, 4 City of Hope National Medical Center, Duarte, CA, 5 Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL
Introduction: The addition of brentuximab vedotin (BV) to combined modality therapy (CMT) for early stage Hodgkin lymphoma (ESHL) has not been previously tested. We prospectively assessed the safety and efficacy of BV+AVD followed by RT for unfavorable ESHL. In cohort 1, patients received involved site RT (ISRT) (Kumar A. et al., Blood 2016). In cohorts 2 and 3, we tested whether reductions in RT dose or volume would be feasible while maintaining efficacy.
Methods: Patients with untreated stage I/II, classical HL with unfavorable risk factors were enrolled. In cohort 3, patients had to have bulky disease >7 cm on CT. Treatment consistent of 4 cycles of BV 1.2 mg/kg with AVD every 2 weeks, followed by 30 Gy ISRT in cohort 1 and 20Gy ISRT in cohort 2. In cohort 3, patients received novel consolidation volume RT (CVRT), where the target volume did not encompass all initial pre-treatment sites of disease, but was limited to post-chemotherapy residual CT abnormalities ≥ 1.5 cm. Though only the CVRT field was treated, theoretical ISRT fields were created. PET/CT after 2 and 4 cycles and after RT were considered negative if Deauville 1–3. The primary endpoint was the rate of complete response.
Results: With median follow up of 2.4 years for cohorts 1 and 2, 1-year PFS was 95% [92%, 98%] and there have been no relapses to date. Reducing the ISRT dose from 30Gy in cohort 1 to 20Gy in cohort 2 resulted in a 24% reduction in mean heart dose and a 32% reduction in mean lung dose.
In cohort 3, 29 patients were enrolled with bulky disease ranging from 7 to 17.5 cm; 9 patients (31%) had advanced stage by GHSG criteria. Twenty-eight patients have completed BV+AVD; 76% and 82% of patients achieved PET negativity after 2 and 4 cycles of therapy, respectively (Table 1). Of 24 patients who completed CMT, 4 patients had a positive end-of-treatment PET: 2 had primary refractory HL, 1 underwent a biopsy that was negative for HL, and 1 is planned for short interval follow-up. A single patient relapsed at 6 months outside the treated CVRT field but within the theoretical ISRT field. CVRT resulted in a 38% decrease in irradiated volume.
Conclusion: BV+AVD x 4 followed by RT for unfavorable ESHL, including bulky disease, is safe and efficacious. Preliminarily, it appears that lowering the ISRT dose to 20Gy does not decrease efficacy. It remains to be seen whether reduced fields will maintain similar efficacy. Updated response data for all patients will be presented at the meeting.