Low‐dose, single‐agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group

SM Ansell, DJ Inwards, KM Rowland Jr… - … Journal of the …, 2008 - Wiley Online Library
SM Ansell, DJ Inwards, KM Rowland Jr, PJ Flynn, RF Morton, DF Moore Jr, SH Kaufmann
Cancer: Interdisciplinary International Journal of the American …, 2008Wiley Online Library
BACKGROUND. The objective of this study was to test a low dose of (25 mg weekly) of the
mammalian target of rapamycin kinase inhibitor temsirolimus for patients with relapsed
mantle cell lymphoma (MCL). METHODS. Patients with relapsed or refractory MCL were
eligible to receive temsirolimus 25 mg intravenously every week as a single agent. Patients
who had a tumor response after 6 cycles were eligible to continue drug for a total of 12
cycles or 2 cycles after complete remission and then were observed without maintenance …
BACKGROUND
The objective of this study was to test a low dose of (25 mg weekly) of the mammalian target of rapamycin kinase inhibitor temsirolimus for patients with relapsed mantle cell lymphoma (MCL).
METHODS
Patients with relapsed or refractory MCL were eligible to receive temsirolimus 25 mg intravenously every week as a single agent. Patients who had a tumor response after 6 cycles were eligible to continue drug for a total of 12 cycles or 2 cycles after complete remission and then were observed without maintenance.
RESULTS
Of 29 enrolled patients, 28 were evaluable for toxicity, and 27 were evaluable for efficacy. The median age was 69 years (range, 51–85 years), 86% of patients had stage IV disease, and 71% had ≥2 extranodal sites. Patients had received a median of 4 prior therapies (range, 1–9 prior therapies), and 50% were refractory to the last treatment. The overall confirmed response rate was 41% (11 of 27 patients; 90% confidence interval [CI], 22%–61%) with 1 complete response (3.7%) and 10 partial responses (37%). The median time to progression in all eligible patients was 6 months (95% CI, 3–11 months), and the median duration of response for the 11 responders was 6 months (range, 1–26 months). Hematologic toxicities were the most common, with 50% (14 of 28 patients) grade 3 and 4% (1 of 28 patients) grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reduction.
CONCLUSIONS
Single‐agent temsirolimus at a dose of 25 mg weekly is an effective new agent for the treatment of MCL. The 25‐mg dose level retained the antitumor activity of the 250‐mg dose with less myelosuppression. Further studies of temsirolimus in combination with other active drugs for MCL and other lymphoid malignancies are warranted. Cancer 2008. © 2008 American Cancer Society.
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