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Updated: Jun 18, 2026
Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma
Published on: March 30, 2018
Temsirolimus in mantle cell lymphoma and other non-Hodgkin lymphoma subtypes
Georg Hess1, Sonali M Smith, Anna Berkenblit
1Department of Haematology/Oncology, Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, Germany. g.hess@3-med.klinik.uni-mainz.de
Abstract:
Temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), has anti-tumor activity in patients with relapsed or refractory mantle cell lymphoma (MCL) and other mature lymphoid neoplasms. mTOR is an intracellular kinase that controls the mRNA translation of many proteins (eg, cyclin D1) that can act as oncogenes and contribute to lymphomagenesis. Characterized by overexpression of cyclin D1, MCL was identified as a disease that might be susceptible to mTOR inhibition. When single-agent temsirolimus was explored in two phase II studies for treatment of patients with relapsed or refractory MCL, it demonstrated anti-tumor activity, with overall response rates of 38% and 41%. Subsequently, a three-arm, randomized phase III trial was conducted to compare two dosing regimens of temsirolimus with investigator's choice of therapy for heavily pretreated patients with relapsed or refractory MCL (N = 162; randomized 1:1:1). Once-weekly intravenous temsirolimus 175 mg for 3 weeks followed by 75 mg once weekly (175/75) significantly improved progression-free survival (hazard ratio = 0.44; P = .0009) versus investigator's choice therapy. Median progression-free survival durations were 4.8 and 1.9 months, respectively. The objective response rates were 22% in the 175/75 group and 2% in the investigator's choice group (P = .0019). For patients receiving temsirolimus, the most frequent grade 3 or 4 adverse events were thrombocytopenia, anemia, neutropenia, and asthenia. The results of this trial established a recommended clinical dose for temsirolimus monotherapy in patients with relapsed or refractory MCL and validated the importance of mTOR in the pathogenesis of advanced MCL. Objective responses also have been reported for other mature B-cell neoplasms (eg, diffuse large B-cell lymphoma or follicular lymphoma) in the phase II setting. Temsirolimus as monotherapy or in combination with other active agents warrants further investigation for treatment of MCL and other non-Hodgkin lymphomas.
Insights
Temsirolimus, an mTOR inhibitor, shows significant anti-tumor activity in relapsed or refractory mantle cell lymphoma (MCL). A specific dosing regimen improved progression-free survival and response rates in a phase III trial.
Area of Science:
- Oncology
- Pharmacology
Background:
- Mantle cell lymphoma (MCL) is characterized by cyclin D1 overexpression, suggesting susceptibility to mTOR inhibition.
- Temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated anti-tumor activity in early phase studies for relapsed/refractory MCL.
Purpose of the Study:
- To compare two temsirolimus dosing regimens against investigator's choice therapy in heavily pretreated patients with relapsed or refractory MCL.
- To establish a recommended clinical dose for temsirolimus monotherapy in this patient population.
Main Methods:
- A three-arm, randomized phase III trial (N=162) compared two temsirolimus regimens (175/75 mg weekly) with investigator's choice therapy.
- Primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR).
Main Results:
- The 175/75 mg temsirolimus regimen significantly improved PFS (HR=0.44, P=.0009) compared to investigator's choice (median PFS 4.8 vs 1.9 months).
- ORR was significantly higher with the 175/75 mg regimen (22% vs 2%, P=.0019).
- Most frequent grade 3/4 adverse events included thrombocytopenia, anemia, neutropenia, and asthenia.
Conclusions:
- Temsirolimus monotherapy, particularly the 175/75 mg regimen, is effective in heavily pretreated patients with relapsed/refractory MCL.
- The study validates mTOR inhibition's importance in advanced MCL pathogenesis.
- Further investigation of temsirolimus for MCL and other non-Hodgkin lymphomas is warranted.