Efficacy and Safety of Liposomal Cytarabine as Intrathecal Prophylaxis in Patients with Diffuse Large B Cell Lymphoma at High Risk of CNS Involvement: A Multicentric Study Including 80 Patients in Spain.

Lymphomatous meningitis (LM) in patients with Diffuse Large B Cell Lymphoma (DLBCL) is usually an early complication and with poor prognosis. Risk factors have been previously identified for this complication. DepoCyte is an extended released liposomal cytarabine formulation (LC) which has demonstrated better efficacy compared to standard cytarabine for the treatment of LM in one randomized clinical trial.

A retrospective study was carried out in 24 Spanish sites including patients diagnosed of DLBCL and at risk of LM – defined by the presence of at least one of the following: retroperitoneal mass ≥ 10 cm; Waldeyer ring, sinus, vertebral or bone, and testicular involvement; LDH more than twice the upper normal limit; bone marrow involvement > 30% and serology VIH+. All patients had received LC as IT prophylaxis for LM in the period April 2005 – June 2009. Main endpoints were effectiveness (leptomeningeal involvement rate) and safety of the IT prophylaxis.

Data from 80 patients were analyzed. Baseline characteristics were: Mean age 55 ± 16 years (range: 18-80 years). Males 74%; Ann Arbor stage IV 54%. All patients received alkylating based regimens, being R-CHOP as the most frequent one (88%). LC was administered as intrathecal prophylactic treatment for LM in all patients.

64 patients completed the IT prophylaxis treatment with a mean of 2,8 ± 0,83 administrations and a median follow up of 17 months (range: 3-40 months) (8 patient still on treatment and 8 patients died before finish prophylaxis). Just one patient (1,6%) had leptomeningeal spread: 76 years old man with primary testicular DLBCL, treated with R-CHOP regime, who did not reach complete response and died after 8 months of follow up due to respiratory failure.

Twenty four patients out of eighty (30%) showed adverse events, being headache the most frequent side effect (27%), and 14% grade IV. Headache was reversible in all cases. Chemical arachnoiditis prophylaxis was given to 70 patients.

This retrospective study has shown that in DLBCL patients and high risk of LM, prophylaxis with LC was feasible and well tolerated. With a median follow up of 17 months (range: 3-40 months) the incidence of LM was 1,6 %. Prospective, randomized comparative studies versus conventional prophylaxis regimes are needed.

Off Label Use: DepoCyte is an extended released liposomal cytarabine formulation (LC) which has demonstrated better efficacy compared to standard cytarabine for the treatment of LM in one randomized clinical trial. Prphylaxis effectiveness..