The promising impact of ibrutinib, a Bruton's tyrosine kinase inhibitor, for the management of lymphoid malignancies.

Lymphoid malignancies comprise a heterogeneous group of disorders originating from clonal proliferation of B or T lymphocytes. Treatment of lymphoid neoplasms has traditionally been pursued with cytotoxic chemotherapy. To improve efficacy and ameliorate the adverse effects associated with classic chemotherapy, molecularly targeted therapy has been developed. At the forefront of clinical development is ibrutinib, an inhibitor of Bruton's tyrosine kinase (Btk). Btk is a protein tyrosine kinase that plays an important role in regulating B-cell signaling. Dysregulated Btk results in uncontrolled B-lymphocyte proliferation, differentiation, and survival. Ibrutinib is currently being studied in numerous malignancies of lymphoid origin including chronic lymphocytic leukemia, mantle cell lymphoma, non-Hodgkin lymphoma, follicular lymphoma, and multiple myeloma. Thus far, ibrutinib has demonstrated very promising results in treatment-naive patients as well as those with relapsed or refractory disease with an acceptable safety profile. In this article, we describe the pharmacology, efficacy, and toxicity profile of ibrutinib and depict the potential role that ibrutinib will play in the treatment paradigm of lymphoid neoplasms.

Predicting acute and persistent neuropathy associated with oxaliplatin.

OBJECTIVES: We sought to predict oxaliplatin-associated peripheral neuropathy during modified FOLFOX6 (mFOLFOX6) therapy. METHODS: Equal numbers of male and female patients with previously untreated, primary or recurrent colorectal cancer were followed through a first course of mFOLFOX6 with 85 mg/m² oxaliplatin every 2 weeks. Accounting for correlation among a subject's cycle, logistic regression estimated per cycle risk of acute (under 14 d) and persistent (14 d or more) neuropathy. Proportional hazards regression predicted time to persistent neuropathy. RESULTS: Among mFOLFOX6 recipients (n = 50, age 58.9 ± 10.1 y), 36% received concomitant bevacizumab. Of the total number of cycles, 94.2% (422/448) were evaluable. Most (84%) subjects reported neuropathy at least once; 74% reported acute and 48% reported persistent symptoms. On multivariate analysis, risk factors shared by acute and persistent neuropathy were body surface area >2.0, acute neuropathy in a past cycle, and lower body weight. In addition, risk of acute neuropathy decreased with age (adjusted for renal function and winter season), whereas risk of persistent neuropathy increased with cumulative dose of oxaliplatin and persistent neuropathy in a past cycle. Concomitant bevacizumab was not a risk factor when administered in stage IV disease but was associated with persistent neuropathy when administered experimentally in stage III. Females had no increased risk of either form of neuropathy. After 3 cycles, weight, body surface area, and prior acute neuropathy predicted time to persistent neuropathy. CONCLUSIONS: Routinely available clinical factors predict acute and persistent neuropathy associated with oxaliplatin. When validated, the proposed prognostic score for persistent neuropathy can help clinicians counsel patients about chemotherapy.