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

Stephen Maxted Ansell, David J. Inwards, Kendrith M. Rowland, Patrick J. Flynn, Roscoe F. Morton, Dennis F. Moore, Scott H Kaufmann, Irene Ghobrial, Paul J. Kurtin, Matthew Maurer, Christine Allmer, Thomas Elmer Witzig

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)508-514
Number of pages7
JournalCancer
Volume113
Issue number3
DOIs
StatePublished - Aug 1 2008

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Mantle-Cell Lymphoma
Neoplasms
Therapeutics
temsirolimus
Confidence Intervals
Sirolimus
Thrombocytopenia
Pharmaceutical Preparations
Phosphotransferases
Maintenance

Keywords

  • CCI-779
  • Mammalian target of rapamycin kinase
  • Mantle cell lymphoma
  • Rapamycin
  • Temsirolimus

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma : A phase 2 trial in the North Central Cancer Treatment Group. / Ansell, Stephen Maxted; Inwards, David J.; Rowland, Kendrith M.; Flynn, Patrick J.; Morton, Roscoe F.; Moore, Dennis F.; Kaufmann, Scott H; Ghobrial, Irene; Kurtin, Paul J.; Maurer, Matthew; Allmer, Christine; Witzig, Thomas Elmer.

In: Cancer, Vol. 113, No. 3, 01.08.2008, p. 508-514.

Research output: Contribution to journalArticle

Ansell, SM, Inwards, DJ, Rowland, KM, Flynn, PJ, Morton, RF, Moore, DF, Kaufmann, SH, Ghobrial, I, Kurtin, PJ, Maurer, M, Allmer, C & Witzig, TE 2008, 'Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: A phase 2 trial in the North Central Cancer Treatment Group', Cancer, vol. 113, no. 3, pp. 508-514. https://doi.org/10.1002/cncr.23580
Ansell, Stephen Maxted ; Inwards, David J. ; Rowland, Kendrith M. ; Flynn, Patrick J. ; Morton, Roscoe F. ; Moore, Dennis F. ; Kaufmann, Scott H ; Ghobrial, Irene ; Kurtin, Paul J. ; Maurer, Matthew ; Allmer, Christine ; Witzig, Thomas Elmer. / Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma : A phase 2 trial in the North Central Cancer Treatment Group. In: Cancer. 2008 ; Vol. 113, No. 3. pp. 508-514.
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abstract = "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.",
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AU - Inwards, David J.

AU - Rowland, Kendrith M.

AU - Flynn, Patrick J.

AU - Morton, Roscoe F.

AU - Moore, Dennis F.

AU - Kaufmann, Scott H

AU - Ghobrial, Irene

AU - Kurtin, Paul J.

AU - Maurer, Matthew

AU - Allmer, Christine

AU - Witzig, Thomas Elmer

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N2 - 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.

AB - 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.

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KW - Rapamycin

KW - Temsirolimus

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