TY - JOUR
T1 - Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma
T2 - A phase 2 study
AU - Ansell, Stephen M.
AU - Tang, Hui
AU - Kurtin, Paul J.
AU - Koenig, Patricia A.
AU - Inwards, David J.
AU - Shah, Keith
AU - Ziesmer, Steven C.
AU - Feldman, Andrew L.
AU - Rao, Radha
AU - Gupta, Mamta
AU - Erlichman, Charles
AU - Witzig, Thomas E.
N1 - Funding Information:
The sponsors of the study were not involved in the collection, analysis, or interpretation of the data. The Cancer Therapy Evaluation Program of the National Cancer Institute was involved in the design and monitoring of the trial. The Predolin Foundation and grant funding from the National Cancer Institute funded the correlative studies. The sponsors were not involved in the writing of the report but reviewed the report on submission. SMA, HT, and PAK had access to the raw data. The corresponding author had full access to all the data and the final responsibility to submit for publication.
Funding Information:
This study was supported in part by grants CA25224 and CA92104 from the National Institutes of Health and the Predolin Foundation . Presented in part at the 51st Annual Meeting of the American Society of Hematology.
PY - 2011/4
Y1 - 2011/4
N2 - Background: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma. Methods: In a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375mg/m2 per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967. Findings: 71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively). Interpretation: mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma. Funding: National Institutes of Health and the Predolin Foundation.
AB - Background: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma. Methods: In a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375mg/m2 per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967. Findings: 71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively). Interpretation: mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma. Funding: National Institutes of Health and the Predolin Foundation.
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U2 - 10.1016/S1470-2045(11)70062-6
DO - 10.1016/S1470-2045(11)70062-6
M3 - Article
C2 - 21440503
AN - SCOPUS:79953182631
SN - 1470-2045
VL - 12
SP - 361
EP - 368
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 4
ER -