Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma.

Activation of the phosphatidylinositol 3-kinase/mechanistic target of rapamycin pathway plays a role in the pathogenesis of non-Hodgkin lymphoma. This multicenter, open-label phase 2 study evaluated buparlisib (BKM120), a pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or refractory non-Hodgkin lymphoma. Three separate cohorts of patients (with diffuse large B-cell lymphoma, mantle cell lymphoma, or follicular lymphoma) received buparlisib 100 mg once daily until progression, intolerance, or withdrawal of consent. The primary endpoint was overall response rate based on a 6-month best overall response by cohort; secondary endpoints included progression-free survival, duration of response, overall survival, safety, and tolerability. Overall, 72 patients (26 with diffuse large B-cell lymphoma, 22 with mantle cell lymphoma, and 24 with follicular lymphoma) were treated. The overall response rates were 11.5%, 22.7%, and 25.0% in patients with diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, respectively; two patients (one each with diffuse large B-cell lymphoma and mantle cell lymphoma) achieved a complete response. The most frequently reported (>20%) adverse events of any grade in the population in which safety was studied were hyperglycemia, fatigue, and nausea (36.1% each), depression (29.2%), diarrhea (27.8%), and anxiety (25.0%). The most common grade 3/4 adverse events included hyperglycemia (11.1%) and neutropenia (5.6%). Buparlisib showed activity in relapsed or refractory non-Hodgkin lymphoma, with disease stabilization and sustained tumor burden reduction in some patients, and acceptable toxicity. Development of mechanism-based combination regimens with buparlisib is warranted. (This study was funded by Novartis Pharmaceuticals Corporation and registered with ClinicalTrials.gov number, NCT01693614).

Langerhans cell sarcoma: Response to radiotherapy.

We present the case of a patient with progressive Langerhans cell sarcoma whose cutaneous lesions and nodal masses were treated with palliative radiotherapy. Response to relatively low doses of radiotherapy was both good and sustained. We recommend a dose of 15-30 Gy depending on treatment intention and volume of the lesions.

Efficacy and safety of liposomal cytarabine in lymphoma patients with central nervous system involvement from lymphoma.

BACKGROUND: : Standard intrathecal chemotherapy for lymphomatous meningitis (LM) is limited by the short cerebrospinal half-lives of the agents used, necessitating frequent administration. Liposomal cytarabine (DepoCyte) has an extended half-life that permits administration at 2- to 4-weekly intervals. METHODS: : Patients with LM who underwent treatment with liposomal cytarabine at treatment centers in Spain between 2004 and 2007 were identified. Data on demographics, treatment, and outcomes were extracted from medical notes and entered, retrospectively, into a database for analysis. RESULTS: : Data on 55 patients with lymphoma (mainly stage IV) and LM were entered into the database. Most patients (n = 36) had diffuse large B-cell lymphoma. The median number of cycles of liposomal cytarabine received was 4 (range, 1-10), and the median follow-up period was 124 days. Complete and partial neurologic responses were achieved in 27 and 12 patients, respectively (overall response rate, 72%), all of whom also showed a cytological response, except for 5 with initially negative cytology. Median time to neurologic progression among responders was 105.5 days. Liposomal cytarabine was generally well tolerated; headache was the most commonly reported adverse effect (n = 17). CONCLUSIONS: : Liposomal cytarabine is effective and well tolerated in the treatment of LM, and should be considered as an agent of choice for the treatment of this complication. Cancer 2009. (c) 2009 American Cancer Society.