Temsirolimus (TEM), an mTOR inhibitor, is approved in the EU for the treatment of pts with rel/refr MCL. A pivotal study demonstrated significantly longer progression free survival (PFS) with TEM (175 mg weekly for 3 weeks followed by 75 mg weekly) in rel/refr MCL pts compared to investigator's choice therapy (4.8 vs 1.9 months (mo); P = 0.0009). To evaluate safety and efficacy of TEM in an unselected clinical routine patient population, a prospective non-interventional study with TEM in rel/refr MCL pts is useful.
A German multicenter registry for rel/refr MCL pts treated with TEM was started in Oct 2009 (NCT00700258). Objectives are the evaluation of the safety profile, tolerability, and anti-tumor activity of TEM as well as patient's profile, and the sequence of systemic therapies.
From Oct 2009 to Feb 2016, 28 study sites recruited 53 pts. Baseline characteristics are available for 53 pts: 69.8% male; median age 74.4 years (range 54.5-96.4); bone marrow involvement in 39.6% of the pts; ECOG PS (n = 52) 0 or 1 in 82.7%, ECOG PS 2 in 17.3%; MIPI score (n = 51): 21.6%, 33.3%, and 45.1% are classified as low, intermediate and high risk at the time of enrollment. Median time between diagnosis and start of treatment with TEM is 2.7 years (range 0.4-14.9).The median number of prior therapies is 2 (range 1-10) with 43.4% of the pts treated in ≥ 4th line. Severe adverse events (drug related) are general, metabolic, psychiatric, skin, renal, gastrointestinal, respiratory (in 1 pt each) and blood system disorders (in 2 pts) and infections (in 4 pts). Efficacy analyses are available for 38 pts and show an objective response in 31.6%, a clinical benefit (CR, PR, MR and SD) in 60.5% and PD in 39.5%. Median PFS for all pts is 3.7 mo. For the subgroup of pts treated with TEM in 2nd and 3rd line PFS is 3.3 mo, for ≥ 4th line pts 4.9 mo.
The registry was started to evaluate the safety and efficacy of TEM in pts with rel/refr MCL in routine clinical practice. 45.1% high-risk pts were included in the analysis. In this comparatively poor-prognosis patient population, TEM showed a predictable, manageable tolerability profile. Efficacy parameters were consistent with published phase III data.
Clinical trial identification
Legal entity responsible for the study
Pfizer Pharma GmbH, Berlin (Dep. Medical Oncology)
Pfizer Pharma GmbH, Berlin, Dep. Medical Oncology
M. Dreyling, G. Hess: Consultant or Advisory Role for Pfizer Honoraria, Pfizer. G. Krekeler, A. Neuhof, M. Woike, D. Kalanovic: employee of Pfizer Pharma GmbH, Germany.