Nivolumab Induces Remission in High- PD-L1 Expressing Aggressive B-Non Hodgkin Lymphoma: A Single Center Experience
Authors: Bohl Stephan R , Schoensteiner Stefan , Huber Henriette , Kuchenbauer Florian , Moeller Peter , Weissinger Stephanie E , Viardot Andreas 
Published: October 2019

Abstract
Patients with relapsed or refractory aggressive B-cell Non-Hodgkin lymphoma (B-NHL) have a poor outcome. Nivolumab (NV) targeting the PD-1 receptor has shown promising results in several malignancies like melanoma, renal and lung carcinoma and Hodgkin lymphoma. Data for aggressive B-NHL are just emerging. PD-L1 expression does not necessarily correlate with response. Among lymphoma subtypes, the expression of PD-L1 seems to vary. So far there are no valid data on PD-L1 expression in aggressive lymphoma under NV treatment.
We retrospectively analyzed seven patients who had aggressive B-NHL with a refractory or relapsed disease after at least 3 regimens and were thereupon treated with NV 3mg/kg once a fortnight. Treatment was initiated after signed informed consent for off-label use. The histologic specimens were analyzed for PD-L1 expression by immunohistochemistry (IHC).
The median age at NV treatment start was 51 years (27-71). The histopathological diagnoses were primary mediastinal B-cell lymphoma (PMBL; n=2), composite lymphoma with diffuse large B-cell (DLBCL) and Hodgkin lymphoma components (n=2), follicular lymphoma transformed into a DLCBL (n=2) and one mediastinal grey zone lymphoma (MGZL). A median of 5 (3-7) prior therapy regimens were given including hematopoietic stem cell transplantation (HSCT) for 3 patients: autologous (n=2) and allogeneic HSCT (n=1), respectively. The lymphoma status was refractory in 2 patients and relapsed in 5 patients. PD-L1 expression was detected in 5 cases, 3 of them showing a positive staining of 10%, 30%, and 50%, respectively, and 2 cases even of 100% of the lymphoma cells. NV was mostly well tolerated (1 pneumonitis completely resolved after systemic steroid therapy, 1 unrelated death caused by septic shock) with a median of 3 (1-17) cycles administered. Response assessment (clinical examination, ultrasound, CT or PET-CT scans) were performed after a median of 3 cycles (2-7), showing regressive and refractory disease in 3 patients, respectively, while 1 patient died prior to response assessment. Among the three responders (2xCR, 1xPR) MGZL and PBML their tumors had high PD-L1 expression of 30% (n=1) and 100% (n=2), respectively. Two responders (one after autologous, one after allogeneic HSCT) are still under treatment. After 14 weeks, one responding patient showed signs of progression of a previously known cerebral lesion (or pseudo progression under immunotherapy). The third responder proceeded to allogeneic HSCT without relevant complications. The PD-L1 expression among the non-responders were 0% (n=2) with progressive disease being the cause of death and 10% (n=1) for the other who is currently receiving alternative therapy.
In conclusion, NV induces remission in heavily pretreated, PD-L1 high expression aggressive B-NHL. The significance of these data are limited due to the small number of patients. Therefore, future results of current phase II trials (NCT02038933) will reveal the role of PD-1 blockade in aggressive B-NHL.

Disclosures
Viardot: Roche: Honoraria; Takeda: Other: travel support; Pfizer: Honoraria; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy.