Abstract P125

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

Background: 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.

Methods: Patients (pts) with RR stage IA/IIA, non-bulky (<10cm) HL after 1 line of therapy received PETCT simulation followed by pembro 200mg IV every 21 days for 4 cycles and PETCT simulation 2-3 weeks later. Pts 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. Pts who progressed (PD) were taken off study. PETCT was done 4-6 weeks after ISRT to document response. The primary endpoint was CMR rate after pembro-RT. Secondary endpoints were response to single agent pembro, 2-year progression free survival (PFS2), and toxicity.

Results: 18 of planned 22 pts enrolled so far, with median age 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 chemo alone in 15 (83%) and combined modality in 3 (17%). 16 (89%) received ABVD, 12 (67%) with <6 cycles. 13 (72%) had relapsed and 5 (28%) had refractory disease.

Of the 15 evaluable pts (3 still on therapy), 5 (33%) had CMR after pembro, 3 (20%) had PMR/SD with negative biopsy, 4 (27%) had PMR with positive biopsy, and 3 (20%) had PD. 12 pts proceeded to ISRT, of whom 5 (42%) with CMR received 20 Gy, 3 (25%) with PMR/SD and negative biopsy received 30 Gy, and 4 (33%) with PMR/SD and positive biopsy received 36-40 Gy. 10 (83% of these pts, 67% overall) achieved CMR. After median follow up of 42 months (3-82), PFS2 was 67% (95% CI 47-95).

3 pts had PD on pembro and 3 had HL relapse at median 12 months (7-70) post-pembro-RT. Among them, 3 are in remission following pembro+chemo or brentuximab vedotin (BV)+nivolumab and SCT, or BV+RT. 3 have unknown status.

Immune-related toxicities were 3 grade 1 rash, and 2 grade 2 hypo/hyperthyroidism. Grade >2 toxicities were 1 grade 3 headache and 1 grade 4 lipase elevation.

Conclusion: Pembro-RT yielded excellent CMR rates and minimal toxicity, suggesting pembro-RT as a potential alternative to SCT in localized, favorable RR HL. Study enrollment continues.

Authors

Alexandra Dreyfuss, Nivetha Ganesan, Alvaro Alencar, Alexander Boardman, Philip Caron, Tiffany Chang, Theresa Davey, Kevin David, Ahmet Dogan, Zachary Epstein-Peterson, Lorenzo Falchi, Beatrice Fregonese, Paola Ghione, Paul Hamlin, Steven Horwitz, Brandon Imber, Andrew Intlekofer, Derek Isrow, Erel Joffe, William Johnson, Anita Kumar, Michael Lariviere, Jennifer Lue, Efrat Luttwak, Michael McNicholas, Zachary Moore, Brittney Munayirji, Ariela Noy, Colette Owens, Lia Palomba, Jaldhi Patel, John Plastaras, Alayna M. Santarosa, Heiko Schöder, Gunjan Shah, Raphael E. Steiner, Robert Stuver, Jakub Svoboda, Pallawi Torka, Santosha Vardhana, Andrew Zelenetz, Gilles Salles, Joachim Yahalom, Craig H. Moskowitz, Alison Moskowitz