Relapsed/refractory ETP-all successfully treated with novel combination therapy venetoclax with nelarabine prior to allogeneic stem cell transplant

Abstract

Anti-Programmed Death Ligand 1 (PD-L1) and Anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) checkpoint inhibitors are increasingly important treatment modalities for solid organ and haematological malignancies. Immune-mediated cytopenias are a rare consequence of checkpoint inhibition and include autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and pure red cell aplasia (PRCA). We report the case of a 75-year-old woman with metastatic lung adenocarcinoma on first line pembrolizumab therapy, presenting with profound anaemia with reticulocytopenia, moderate thrombocytopenia and haemolysis post red cell transfusion. Bone marrow biopsy showed absence of erythroid precursors, in keeping with PRCA, and presence of megakaryopoiesis, consistent with ITP. Extensive testing for the aetiology of haemolysis did not reveal a clear diagnosis. She was treated with prednisolone initially, and red cell transfusion withheld. Due to inadequate response she was given intravenous immunoglobulin therapy which resulted in vigorous reticulocyte response and improvement in haemoglobin and platelet count. To date she has required no escalation of therapy. In summary, we describe a rare case of concurrent PRCA and ITP during treatment with PD-L1 inhibitor therapy, and haemolysis of cryptic cause. Treating clinicians should be vigilant for the development of autoimmune haematological syndromes during checkpoint inhibitor therapy. Treatment with conventional immunosuppression is usually successful.