Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review.

BACKGROUND: Immune checkpoint inhibitors (CPI) are widely used in modern oncology and have improved the prognosis of lung cancer, malignant melanoma, and other malignancies. Unlike cytotoxic chemotherapy, drugs such as nivolumab, pembrolizumab, and ipilimumab are associated with immune-related adverse effects. We recently observed a patient with lung cancer who developed a fulminant warm antibody autoimmune hemolytic anemia (AIHA). OBJECTIVES: Investigate the frequency and prognosis of AIHA secondary to CPI in a public database and review the literature. RESULTS: A total of 68 cases were identified in the database of the Food and Drug Administration (FDA), 43 were associated with nivolumab, 13 with pembrolizumab, seven with ipilimumab, and five with atezolizumab. All episodes of AIHA were listed as serious. If the total number of adverse events cases reported to the FDA is taken as a reference, AIHA is rare, but occurred more frequently with PD-1 or PD-L1 targeting agents (0.15%-0.25%) than with CTLA-4 inhibitors (0.06%). In addition to our case, the literature review identified 11 similar cases. Most cases of AIHA responded to steroids, but two of 12 were fatal. CONCLUSION: We describe AIHA as a new and serious immune-related side effect of CPI. Early aggressive management is necessary.

MALT1 Inhibition Is Efficacious in Both Naïve and Ibrutinib-Resistant Chronic Lymphocytic Leukemia.

The clinical efficacy displayed by ibrutinib in chronic lymphocytic leukemia (CLL) has been challenged by the frequent emergence of resistant clones. The ibrutinib target, Bruton's tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK. Recent findings show that MI-2, a small molecule inhibitor of the para-caspase MALT1, is effective in preclinical models of another type of BCR pathway-dependent lymphoma. We therefore studied the activity of MI-2 against CLL and ibrutinib-resistant CLL. Treatment of CLL cells in vitro with MI-2 inhibited MALT1 proteolytic activity reduced BCR and NF-κB signaling, inhibited nuclear translocation of RelB and p50, and decreased Bcl-xL levels. MI-2 selectively induced dose and time-dependent apoptosis in CLL cells, sparing normal B lymphocytes. Furthermore, MI-2 abrogated survival signals provided by stromal cells and BCR cross-linking and was effective against CLL cells harboring features associated with poor outcomes, including 17p deletion and unmutated IGHV Notably, MI-2 was effective against CLL cells collected from patients harboring mutations conferring resistance to ibrutinib. Overall, our findings provide a preclinical rationale for the clinical development of MALT1 inhibitors in CLL, in particular for ibrutinib-resistant forms of this disease. Cancer Res; 77(24); 7038-48. ©2017 AACR.

Pituitary apoplexy: a rare complication of leuprolide therapy in prostate cancer treatment.

Gonadotropin-releasing hormone agonists, used widely in the treatment of metastatic prostate cancer and hormone receptor-positive breast cancer, are associated with a rare but potentially fatal outcome of pituitary apoplexy (PA). An 85-year-old man presented with sudden onset of headache, left eye pain, sensitivity to light, nausea and vomiting. The symptoms started 4 hours after initiation of leuprolide therapy for treatment of recently diagnosed metastatic prostate carcinoma. Radiological imaging of the brain demonstrated a heterogeneously enlarged pituitary gland measuring 19×16×13 mm and T1-hyperintense signal compatible with pituitary haemorrhage. Hormone function tests were indicative of panhypopituitarism, confirming the diagnosis of PA. Due to age, the patient was started on hormonal replacement therapy and eventually symptoms improved.

Diffuse large B-cell lymphoma: A metabolic disorder?

UNLABELLED: Patient Male, 81 FINAL DIAGNOSIS: Non-Hodgkin lymphoma Symptoms: General weakness • hypoglycemia • metabolic acidosis MEDICATION: - Clinical Procedure: - Specialty: Hematology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement. CASE REPORT: We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels. CONCLUSIONS: The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis.