pci-32765 and Red-Cell-Aplasia--Pure

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are common complications of CLL. The optimal treatment of steroid refractory AIHA/PRCA is not well established. We conducted a multicenter study of ibrutinib and rituximab in patients with relapsed/refractory to steroids AIHA/PRCA and underlying CLL. Protocol included induction (ibrutinib 420 mg/day and rituximab, 8 weekly and 4 monthly infusions) and maintenance phase with ibrutinib alone until progression or unacceptable toxicity. Fifty patients were recruited (44-warm AIHA, 2-cold AIHA, 4-PRCA). After the induction 34 patients (74%) have achieved complete response, 10 (21.7%) partial response. Median time to hemoglobin normalization was 85 days. With regards to CLL response 9 (19%) patients have achieved CR, 2 (4%) patients-stabilization and 39 (78%)-PR. The median follow-up was 37.56 months. In AIHA group 2 patients had a relapse. Among 4 patients with PRCA 1 patient did not respond, and 1 patient had a relapse after CR, 2 remained in CR. The most common adverse events were neutropenia (62%), infections (72%), gastrointestinal complications (54%). In conclusion ibrutinib in combination with rituximab is an active second-line treatment option for patients with relapsed or refractory AIHA/PRCA and underlying CLL.

Topics: Anemia, Hemolytic, Autoimmune; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence; Red-Cell Aplasia, Pure; Rituximab; Steroids; Thrombocytopenia

Chronic lymphocytic leukemia (CLL) has long been known for its complications related to immune deregulation, of which autoimmune cytopenias (AIC) were frequently reported. Ibrutinib has dramatically changed the overall prognosis of patients with CLL. However, whether ibrutinib can induce or aggravate AIC in CLL patients is still disputable. Here we report a CLL patient with pure red cell aplasia (PRCA) occurring during ibrutinib treatment and review available data to discuss the possible role of ibrutinib in developing AIC.. A 70-year-old female was diagnosed with CLL with indications to initiate ibrutinib treatment given progressive bulky disease. She was admitted for advanced fatigue on the 14th day of ibrutinib monotherapy. A complete blood count revealed severe anemia of hemoglobin (Hb) 37 g/L and a meager reticulocyte count. After excluding other conditions that could cause anemia, PRCA was diagnosed as a complication of CLL.. Our case demonstrates a need to evaluate the risk of developing AIC before initiating ibrutinib. For patients with high-risk factors for AIC episodes, the transient addition of other immunosuppressive therapies should be taken into consideration.

Topics: Aged; Cyclosporine; Female; Humans; Immunoglobulins, Intravenous; Leukemia, Lymphocytic, Chronic, B-Cell; Prednisone; Red-Cell Aplasia, Pure; Thrombocytopenia

Topics: ABO Blood-Group System; Adenine; Blood Group Incompatibility; Hematopoietic Stem Cell Transplantation; Humans; Piperidines; Red-Cell Aplasia, Pure

Topics: Adenine; Aged; Anemia, Hemolytic, Autoimmune; Antineoplastic Agents; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Red-Cell Aplasia, Pure; Steroids; Virus Diseases

Topics: Adenine; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Protein Kinase Inhibitors; Red-Cell Aplasia, Pure

Topics: Adenine; Aged; Antineoplastic Agents; Biomarkers; Biopsy; Blood Cell Count; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Red-Cell Aplasia, Pure; Treatment Outcome