Effect of prognostic classification on temsirolimus efficacy and safety in patients with relapsed or refractory mantle cell lymphoma: a retrospective analysis

Experimental Hematology & Oncology

Pádraig J Moran³  Lisa Kang⁴  Jorge Romaguera⁵  Fritz Offner²  Christian Gisselbrecht¹  Michael Crump⁶  Bertrand Coiffier⁸  Georg Hess⁷ 

[1] Hôpital Saint-Louis, Paris, France;Ghent University Hospital, Ghent, Belgium;Prizer Inc, Dublin, Ireland;Pfizer Inc, Cambridge, MA, USA;The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Princess Margaret Hospital, Toronto, ON, Canada;Department of Hematology/Oncology, Johannes Gutenberg University, Langenbeckstr. 1, Mainz DE 55101, Germany;Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Benite, France

关键词: Safety;    Efficacy;    Temsirolimus;    Risk;    Prognostic;    Mantle cell lymphoma;   

Others  :  1211750
DOI  :  10.1186/s40164-015-0006-1

 received in 2015-01-21, accepted in 2015-03-18,  发布年份 2015

【 摘 要 】

Background

Temsirolimus, a selective inhibitor of the mammalian target of rapamycin, has demonstrated clinical benefit versus investigator’s choice (INV) of therapy in patients with relapsed/refractory mantle cell lymphoma (MCL).

Methods

This post hoc study retrospectively assigned simplified Mantle Cell Lymphoma International Prognostic Index (MIPI) scores (ie, secondary MIPI) based on parameters at the time of randomization in patients with MCL (N = 162) who received temsirolimus 175 mg once weekly for 3 weeks followed by once-weekly 75 mg or 25 mg or the INV of active therapy. Outcomes were analyzed according to the low-, intermediate- or high-risk category.

Results

Patient distribution by MIPI risk category was 31%, 39%, and 30% in the low-, intermediate-, and high-risk groups, respectively. Among patients in all categories, objective response rate (complete response + partial response) was higher in patients in the temsirolimus 175/75-mg group versus the INV group, respectively: 42% versus 0% (low-risk); 33% versus 5% (intermediate-risk); 10% versus 0% (high-risk). Median progression-free survival was significantly longer with temsirolimus 175/75 mg versus INV, respectively, in patients with intermediate (4.3 vs 1.9 months; P = 0.035) or high (4.5 vs 1.6 months; P = 0.0025) risk, and a trend toward improvement was observed in patients with low risk (5.3 vs 2.6 months; P = 0.091). Improvement in median overall survival was observed with temsirolimus 175/75 mg versus INV in low-risk patients (18.0 vs 10.5 months, respectively; P = 0.069).

Conclusions

This analysis suggests that, compared with INV, temsirolimus demonstrated benefit in all MIPI risk categories in patients with MCL. In all treatment groups, patients with high secondary MIPI scores at baseline faced a dismal prognosis.

Trial registration

ClinicalTrials.gov NCT00117598 webcite.

【 授权许可】

   
2015 Hess et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Chandran R, Gardiner SK, Simon M, Spurgeon SE. Survival trends in mantle cell lymphoma in the United States over 16 years 1992–2007. Leuk Lymphoma. 2012; 53:1488-93.
• [2]Dietrich S, Tielesch B, Rieger M, Nickelsen M, Pott C, Witzens-Harig M et al.. Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma. Cancer. 2011; 117:1901-10.
• [3]Dreyling M, Kluin-Nelemans HC, Bea S, Klapper W, Vogt N, Delfau-Larue MH et al.. Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma: report of the 11th annual conference of the European mantle cell lymphoma network. Leuk Lymphoma. 2013; 54:699-707.
• [4]Herrmann A, Hoster E, Zwingers T, Brittinger G, Engelhard M, Meusers P et al.. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol. 2009; 27:511-8.
• [5]Argyriou P, Economopoulou P, Papageorgiou S. The role of mTOR inhibitors for the treatment of B-cell lymphomas. Adv Hematol. 2012; 2012:435342.
• [6]Coiffier B, Ribrag V. Exploring mammalian target of rapamycin (mTOR) inhibition for treatment of mantle cell lymphoma and other hematologic malignancies. Leuk Lymphoma. 2009; 50:1916-30.
• [7]Perez-Galan P, Dreyling M, Wiestner A. Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era. Blood. 2011; 117:26-38.
• [8]Ansell SM, Inwards DJ, Rowland KM, Flynn PJ, Morton RF, Moore DF et al.. Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North central cancer treatment group. Cancer. 2008; 113:508-14.
• [9]Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C et al.. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009; 27:3822-9.
• [10]Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P et al.. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol. 2005; 23:5347-56.
• [11]Fujiwara Y, Kiyota N, Chayahara N, Suzuki A, Umeyama Y, Mukohara T et al.. Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients. Invest New Drugs. 2011; 30:1055-64.
• [12]Dreyling M, Thieblemont C, Gallamini A, Arcaini L, Campo E, Hermine O et al.. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol. 2013; 24:857-77.
• [13]Geisler CH, Kolstad A, Laurell A, Raty R, Jerkeman M, Eriksson M et al.. The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT). Blood. 2010; 115:1530-3.
• [14]Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC et al.. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008; 111:558-65.
• [15]Todorovic M, Balint B, Andjelic B, Stanisavljevic D, Kurtovic NK, Radisavljevic Z et al.. Outcome prediction of advanced mantle cell lymphoma by international prognostic index versus different mantle cell lymphoma indexes: one institution study. Med Oncol. 2012; 29:2212-9.
• [16]Vose JM. Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical management. Am J Hematol. 2012; 87:604-9.
• [17]Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS et al.. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013; 369:507-16.