ALBERT

Description: Introduction Temsirolimus (TEM) is an mTOR inhibitor EMA approved for the treatment of patients (pts) with relapsed or refractory (R/R) mantle cell lymphoma (MCL). In a phase III trial TEM 175mg weekly for 3 weeks followed by 75mg weekly significantly improved PFS (4.8 months)  and objective response rate (22%) compared with investigator’s choice (1.8 months, 2% respectively). TEM has also been tested in combination with rituximab (RTX) in a phase II trial with encouraging efficacy results (ORR 59%, median time to progression 9.7 months) even in rituximab-refractory pts. However, few data have been reported on the use of TEM in everyday clinical practice. Methods Sixteen Spanish centres participated in this retrospective, observational and multicenter study: Inclusion criteria were as follows: pts ≥18 at the time of treatment, confirmed diagnosis of R/R MCL treated with TEM between January 1st 2010 and  December 31st 2012. Endpoints were overall response (ORR), partial response (PR) and complete response (CR) rate, toxicity as CTCAE v3.0 of NCI scale and overall survival (OS) and progression free survival (PFS).This study was approved by the Ethic Committee of all participant sites (PFI-TEM-2010-01). Results A total of 24 patients were included, 15 pts treated with TEM in monotherapy (TEM 175mg weekly for 3 weeks followed by 75mg weekly) and 9 in combination with RTX (TEM 25mg/week plus RTX 375mg/m2 per week during the first cycle and a single dose of RTX every other 28-day cycle). 22 were male and the median age was 71 (range 53 to 84). Regarding histology grade, 17 (74%) pts had classic, 1 (4.3%) blastoid and 5 (21.7%) unknown. According to simplified MIPI prognostic score, 6 (26.1%) pts had low risk, 10 (43.5%) intermediate risk and 7 (30.4%) high risk. Five pts had 10-40% of Ki 67 index, 3 had 〉40% and 14 pts unknown. Median number of prior therapies in TEM monotherapy cohort was 2 (range 1 to 7) and 4 (range 2 to 8) in the combination cohort. Median duration of therapy was 3.07 months in the TEM monotherapy cohort and 2.03 months in the combination cohort. The overall response rate (ORR) with TEM in monotherapy was 60% (40% CR and 20% PR) and 6.7% of disease stabilization. For those patients treated with TEM plus RTX, the ORR was 78% (56% CR and 22% PR) and 20% of disease stabilization. Median PFS for patients who reached CR in TEM monotherapy cohort was 12.73 months (95%CI, 1.28 to 24.19) and 10.93 months (95%CI, 1.40 to 20.46) in the combination cohort. Overall the median PFS for all patients was 7.30 months (95%CI, 2.36 to 12.24). Two pts underwent allogeneic stem cell transplantation after successful TEM monotherapy treatment. In terms of tolerability, 13 pts of 15 developed at least one adverse event (AE) in the TEM monotherapy cohort and 5 pts of 9 in the combination cohort. Most common AE (all grades) were thrombocitopenia (75%) in both cohorts, rash (37%), diarrhea (12%), hyperglucemia  (12%), hyperlipemia (8%), mucositis (8%) and neumonitis (8%). Most common G3/4 adverse event was thrombocytopenia (33%). Conclusions Although this is a small sample size, TEM efficacy in this study seems to be higher compared to previous Phase II and III trials with an acceptable toxicity profile in pts with MCL. The median PFS in the combination therapy cohort was surprisingly lower than in the monotherapy cohort which may be explained by differences in clinical features between both groups. Disclosures: Off Label Use: Use of temsirolimus in combination with rituximab. Morán:Pfizer: Employment. Viqueira:Pfizer: Employment.