Venetoclax-failed monotherapy in B-lymphoproliferative neoplasms responded to combination of venetoclax with immunochemotherapy: A report of two cases.

Abstract Venetoclax (ABT-199), an inhibitor of B-cell lymphoma 2 (BCL-2) protein, has been approved for the treatment of chronic lymphocytic leukaemia (CLL) and in late-phase clinical trials for B-cell non-Hodgkin's lymphoma (B-NHL) and other malignancies. However, patients who failed under venetoclax treatment have a very poor prognosis. We describe here two patients with B-lymphoproliferative neoplasms (CLL, B-NHL), who failed on venetoclax monotherapy, and achieved a good overall response after adding a combination of rituximab and cyclophosphamide to venetoclax. In both fragile, heavily pretreated patients, the combination of venetoclax with immunochemotherapy resulted in the clinically significant and almost year-long regression of lymph nodes and bone marrow tumour cell infiltration, respectively. Our data highlights the perspective combination of venetoclax with immunochemotherapy for patients who suboptimally responded or failed on venetoclax monotherapy.