Luca Castagna1, Massimo Magagnoli1, Rita Mazza1, Lucia Morello1, Francesca Ricci1, Stefania Bramanti1, Barbara Sarina1, Jacopo Mariotti1, Chiara De Philippis1, Simona Sica2, Marcello Rodari3, Martina Sollini3, Margarita Kirienko3, Arturo Chiti3,4, Armando Santoro1,4, Carmelo Carlo-Stella1,4
1Hematology, Humanitas Cancer Center, Humanitas Research Hospital, Rozzano-Milano, Italy,2Fondazione Policlinico Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore, Roma, Italy,3Nuclear Medicine, Humanitas Research Hospital, Rozzano-Milano, Italy,4Department of Biomedical Sciences, Humanitas University, Rozzano-Milano, Italy
Introduction: Phase 1/2 trials using PD-1 inhibitors in relapsed/refractory (r/r) cHL who failed brentuximab vedotin (BV) and autologous SCT (Auto-SCT) showed unprecedented rates of complete/partial response (CR/PR) and durable responses. However, the absence of a plateau in the PFS curves indirectly suggests that Allo-SCT may represent a consolidation therapy for patients responding to PD-1 therapy.
Methods: From Nov 2014 to Dec 2016, 37 r/r cHL enrolled in the CA209–205 and CA209–254 trials (median age, 32 years; range, 18–81) received nivolumab until CR, PR (tumor burden reduction >80%) or progressive disease (PD). At study entry, 30 patients (81%) had primary refractory disease, 32 (86%) had failed BV and 33 (89%) Auto-SCT.
Results: After a median duration of nivolumab therapy of 10 months (range, 3–33), 16 cases (43%) experienced CR/PR and 21 cases (57%) PD. Fourteen of 16 responding patients were allografted. Thirteen of 21 patients in PD after Nivolumab achieved an objective response (CR or PR) after additional chemotherapy or radiotherapy and were finally allografted. Overall, 27 of 37 patients were allografted with a median follow-up of 19 months for survivors (range, 3–40). The median time from last nivolumab to Allo-SCT was 47 days (range, 23 – 372). At Allo-SCT, 18 patients (67%) were in CR, 8 (30%) in PR and 1 (3%) in PD. Donors were haploidentical sibling (n = 19), matched sibling (n = 4), or matched unrelated (n = 4). Stem cell source was bone marrow (n = 11) and peripheral blood (n = 16). Five patients died due to disease progression (n = 1) or non-relapse mortality (NRM, n = 4, including aGVHD, CMV pneumonia, heart failure, PTLD). The 2-year cumulative incidence (CI) of relapse and NRM was 3.8% and 12%, respectively. The CI of grade 2–4 and grade 3–4 acute GVHD was 46% and 10%, respectively; the 1-year CI of cGVHD was 22%. Five patients experienced macrophage activation syndrome, 13 cytokine release syndrome, 1 posterior reversible encephalopathy syndrome. The 2-year OS and PFS were 74% (95% CI, 45 to 89) and 75% (95% CI, 46 to 90), respectively.
Conclusions: Allo-SCT after nivolumab or nivolumab plus chemotherapy has a manageable toxicity and is associated with an unprecedented low relapse incidence. PD-1 inhibitors represent a paradigm shift in the treatment of relapsed and refractory cHL.