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.