330 - Pembrolizumab and Involved Site Radiation Therapy Alone as an Alternative to Transplant in Patients with Localized Failure following Chemotherapy for Hodgkin Lymphoma: A Prospective Multicenter Phase II Study
Presenter(s)
A. Dreyfuss1, N. Ganesan2, B. S. Imber3, D. Isrow4, M. J. LaRiviere5, J. P. Plastaras5, J. Svoboda6, J. Yahalom3, C. Moskowitz7, and A. J. Moskowitz2; 1University of Miami, Miami, FL, 2Memorial Sloan Kettering Cancer Center, New York, NY, 3Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 4University of Miami Miller School of Medicine, Miami, FL, 5Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, 6Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, 7University of Miami, Miami, FL, United States
Purpose/Objective(s): Chemotherapy (chemo) followed by stem cell transplant (SCT) is standard of care for relapsed/refractory (RR) Hodgkin Lymphoma (HL). In a phase II study, we evaluated pembrolizumab (pembro) with involved site radiation therapy (ISRT) as an alternative salvage approach for localized favorable relapse.
Materials/Methods: Patients with RR stage IA/IIA, non-bulky (<10cm) HL after one line of therapy had a PETCT simulation followed by pembro 200mg IV q 21d for 4 cycles and PETCT simulation 3w later. Patients then received ISRT per response as follows: 1) 20 Gy for complete metabolic response (CMR) defined by Deauville Score (DS) 1-3; 2) 30 Gy for partial metabolic response (PMR) or stable disease (SD) (DS 4-5) and negative biopsy; or 3) 36-40 Gy for PMR/SD and positive biopsy. Patients who progressed (PD) were taken off study. PETCT response was documented 4-6 weeks after ISRT. The primary endpoint was CMR rate after pembro-RT. Secondary endpoints were response to single agent pembro, 2-year progression free survival (PFS), and toxicity.
Results: 22 of planned 22 patients enrolled. Among the 18 who have completed therapy, median age was 37 (range 22-66). 3 (17%) had stage I, 14 (78%) stage II, and 1 had an unspecified limited stage at initial diagnosis. Frontline therapy was chemotherapy alone in 15 (83%) and combined modality in 3 (17%). 16 (89%) received doxorubicin/hydroxydaunorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), 12 (67%) with <6 cycles. 13 (72%) had relapsed and 5 (28%) had refractory disease. Of the 18 evaluable patients (4 still on therapy), 6 (33%) had CMR after pembro, 3 (17%) had PMR/SD with negative biopsy, 5 (28%) had PMR with positive biopsy, and 4 (22%) had PD. 14 patients proceeded to ISRT, of whom 6 (43%) with CMR received 20 Gy, 3 (21%) with PMR/SD and negative biopsy received 30 Gy, and 5 (36%) with PMR/SD and positive biopsy received 36-40 Gy. 12 (86% of these patients, 67% overall) achieved CMR. After median follow up of 34 months (3-82), 2-year PFS was 67% (95% CI 46-92).
Four patients progressed on pembro and three relapsed after a median of 12 months (range 7-70) from completion of pembro-RT. Among the patients with PD during or after pembro-RT, three are currently in remission while the status for the others are unknown. Subsequent treatment for the three patients currently in remission included pembro plus gemcitabine/vinorelbine/liposomal doxorubicin followed by ASCT (n=1), brentuximab vedotin (BV) plus nivolumab followed by ASCT (n=1) and 2 doses of BV followed by additional RT (n=1). Immune-related toxicities were 3 (17%) grade 1 rash, and 2 (12%) grade 2 hypo/hyperthyroidism. Grade >2 toxicities were 1 (6%) grade 3 headache, 1 (6%) grade 3 pruritis, and 1 (6%) grade 4 lipase elevation.Conclusion: Pembro-RT yielded excellent CMR rates and minimal toxicity. These data suggest pembro-RT as a potential alternative to high dose chemo and SCT in localized, favorable relapsed/refractory HL. Enrollment to the study is complete and data will be updated prior to the meeting.