PB1825 NIVOLUMAB IN B‐CELL LYMPHOMA, UNCLASSIFIABLE, WITH FEATURES INTERMEDIATE BETWEEN DIFFUSE LARGE B‐CELL LYMPHOMA AND CLASSICAL HODGKIN LYMPHOMA
Authors: Yakimovich K.P. , Mikhailova N.B. , Lepik K.V. , Smykova O.G. , Kondakova E.V. , Borzenkova E.S. , Kozlov A.V. , Zalyalov Y.R. , Stelmakh L.V. , Darskaya E.I. , Moiseev I.S. , Afanasyev B.V. 
Published: June 2019

Background:There is no standard therapy for B‐cell lymphoma, unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and Hodgkin lymphoma (intermediate DLBCL/HL) because of its recent identification as a distinct entity by WHO and rarity of described cases. At the same time, patients with relapsed and refractory disease represent the group with dismal prognosis. Recent studies revealed that intermediate DLBCL/HL has frequent chromosome 9p24.1 alterations and hence the use of PD‐1 blockade might be effective treatment option. To our knowledge, only 3 cases with this approach were published and had positive results (Melani C. et al, N Engl J Med, 2017).Aims:We aimed to evaluate safety and efficacy of PD‐1‐inhibitor nivolumab in relapsed and refractory intermediate DLBCL/HL.Methods:We analyzed data of 5 patients with relapsed or refractory intermediate DLBCL/HL. The diagnosis was confirmed by immunohistochemical (IHC) staining of the biopsy specimens according to the morphological features of intermediate DLBCL/HL. Response was evaluated by PET‐CT and was defined according to LYRIC criteria. PDL‐1 expression was evaluated in three patients. In these patients high PD‐L1 level (100%, 100% and 90%) on the tumor cells was confirmed.Results:This analysis includes 3 men and 2 women. The median age at the time of diagnosis was 33 years old (range, 22‐87). Four patients received Hodgkin's lymphoma regimen as the first line therapy and 1 patient received non‐Hodgkin's lymphoma regimen. The median number of prior therapy lines was 4 lines (range, 2‐6 lines). High dose chemotherapy and autologous stem cell transplantation (SCT) was performed in 2 patients with no durable response. Immunotherapy was started at disease progression in all cases with the stages of disease 3‐4. Nivolumab was administered in the following regimens: as monotherapy in two patients, in combination with rituximab in one patient, in combination with brentuximab vedotin (BV) plus R‐EPOCH therapy in one patient and as monotherapy, nivolumab/bendamustine combination and nivolumab/BV combination in one patient. The median number of nivolumab infusions was 7 (range, 6‐24). An objective response was reached in 4 (80%) patients including 2 (40%) complete responses and 2 (40%) partial responses. One (20%) patient had an intermediate response according to LYRIC criteria. At a median follow‐up of 7 months (range, 5‐16) 4 (80%) patients are alive without signs of relapse/progression of disease and 1 patient died due to disease progression. Adverse events of nivolumab‐containing treatment included severe neutropenia and mild infusion reaction in one patient. As consolidation, haploidentical hematopoetic stem cell transplantation was perfomed in one patient, and allo‐SCT is currently scheduled in 2 patients.Summary/Conclusion:According to the data nivolumab‐containing treatment can induce objective response with acceptable safety profile and may represent possible salvage treatment option in heavily pretreated patients with intermediate DLBCL/HL. This and other observations serve as the rationale for assessment of nivolumab‐containing regimen for the treatment of intermediate DLBCL/HL in the prospective trials.