Drug Evaluation

Pralatrexate: treatment of T-cell non-Hodgkin’s lymphoma

Department of Internal Medicine (Hematology), Yale University School of Medicine, 333 Cedar Street, PO Box 208032, New Haven, CT 06520, USA

Search for more papers by this author

Lisa Barbarotta

Yale-New Haven Hospital, 20 York Street, New Haven, CT 06520, USA

Search for more papers by this author

Francine Foss

* Author for correspondence

Department of Internal Medicine (Hematology), Yale University School of Medicine, 333 Cedar Street, PO Box 208032, New Haven, CT 06520, USA.

Search for more papers by this author

Email the corresponding author at francine.foss@yale.du

Published Online:19 Dec 2012https://doi.org/10.2217/fon.12.168

View article

Abstract

Pralatrexate is a folate analogue metabolic inhibitor manufactured by Allos Therapeutics, Inc., a wholly-owned subsidiary of Spectrum Pharmaceuticals, Inc. In both preclinical and clinical studies, pralatrexate demonstrated activity in lymphoma. Pralatrexate was US FDA approved for the treatment of relapsed/refractory peripheral T-cell lymphoma in 2009. Approval was based on data from the PROPEL trial that demonstrated an overall response rate of 29% in a heavily pretreated patient population. The dose and schedule of pralatrexate is 30-mg/m² weekly for 6 weeks, given in 7-week cycles. Folate and vitamin B12 supplementation are required to minimize toxicity. The most common toxicities are mucositis, thrombocytopenia, nausea and fatigue.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

1 Vose JM. Peripheral T-cell non-Hodgkin’s lymphoma. Hematol. Oncol. Clin. North Am.22(5),997–1005 (2008).Crossref, Medline, Google Scholar
2 Foss FM, Zinzani PL, Vose JM, Gascoyne RD, Rosen ST, Tobinai K. Peripheral T-cell lymphoma. Blood117(25),6756–6767 (2011).Crossref, Medline, CAS, Google Scholar
3 Vose J, Armitage J, Weisenburger D, Project IT-CL. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J. Clin. Oncol.26(25),4124–4130 (2008).▪ Describes the outcomes for patients with aggressive T-cell lymphoma.Crossref, Medline, Google Scholar
4 AbouYabis AN, Shenoy PJ, Flowers C, Lechowicz MJ. Response and survival rates in patients with peripheral T-cell lymphoma treated with anthracycline-based regimens: a comprehensive meta-analysis [abstract]. Blood110(11), Abstract 3452 (2007).Crossref, Google Scholar
5 NCCN Guidelines™ Non-Hodgkin’s Lymphomas Panel. NCCN clinical practice guidelines in oncology: non-Hodgkin’s lymphomas. National Comprehensive Cancer Network, Fort Washington, PA, USA (9 July 2012).Google Scholar
6 Enblad G, Hagberg H, Erlanson M et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood103(8),2920–2924 (2004).Crossref, Medline, CAS, Google Scholar
7 Zinzani PL, Musuraca G, Tani M et al. Phase II trial of proteasome inhibitor bortezomib in patients with relapsed or refractory cutaneous T-cell lymphoma. J. Clin. Oncol.25(27),4293–4297 (2007).Crossref, Medline, CAS, Google Scholar
8 Dang NH, Pro B, Hagemeister FB et al. Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma. Br. J. Haematol.136(3),439–447 (2007).Crossref, Medline, CAS, Google Scholar
9 Sallah S, Wan JY, Nguyen NP. Treatment of refractory T-cell malignancies using gemcitabine. Br. J. Haematol.113(1),185–187 (2001).Crossref, Medline, CAS, Google Scholar
10 Czuczman MS, Porcu P, Johnson J et al. Results of a Phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901. Leuk. Lymphoma48(1),97–103 (2007).Crossref, Medline, CAS, Google Scholar
11 Dueck GS, Chua N, Prasad A et al. Activity of lenalidomide in a Phase II trial for T-cell lymphoma: report on the first 24 cases. J. Clin. Oncol.27(15S), Abstract 8524 (2009).Crossref, Medline, Google Scholar
12 Mercieca J, Matutes E, Dearden C, Maclennan K, Catovsky D. The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. J. Clin. Oncol.12(12),2588–2593 (1994).Crossref, Medline, CAS, Google Scholar
13 Tsimberidou AM, Giles F, Duvic M, Fayad L, Kurzrock R. Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an M.D. Anderson Cancer Center series. Cancer100(2),342–349 (2004).Crossref, Medline, CAS, Google Scholar
14 O’Connor OA, Pro B, Pinter-Brown L et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J. Clin. Oncol.29(9),1182–1189 (2011).▪▪ Describes the PROPEL trial that led to US FDA approval of pralatrexate in peripheral T-cell lymphoma.Crossref, Medline, Google Scholar
15 Piekarz RL, Frye R, Prince HM et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood117(22),5827–5834 (2011).Crossref, Medline, CAS, Google Scholar
16 Coiffier B, Pro B, Prince HM et al. Results from a pivotal, open-label, Phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J. Clin. Oncol.30(6),631–636 (2012).Crossref, Medline, CAS, Google Scholar
17 Pro B, Advani R, Brice P et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a Phase II study. J. Clin. Oncol.30(18),2190–2196 (2012).Crossref, Medline, CAS, Google Scholar
18 Younes A, Bartlett NL, Leonard JP et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N. Engl. J. Med.363(19),1812–1821 (2010).Crossref, Medline, CAS, Google Scholar
19 Thompson CA. FDA approves pralatrexate for treatment of rare lymphoma. Am. J. Health Syst. Pharm.66(21),1890 (2009).Crossref, Medline, Google Scholar
20 Sirotnak FM, Schmid FA, Samuels LL, Degraw JI. 10-ethyl-10-deaza-aminopterin: structural design and biochemical, pharmacologic, and antitumor properties. NCI Monogr. (5),127–131 (1987).Medline, Google Scholar
21 Sirotnak FM, Degraw JI. Selective antitumor action of folate analogs. In: Folate Antagonists as Therapeutic Agents. Sirotnak FM, Burchall JJ, Ensminger WD, Montgomery JA (Eds). Academic Press, Inc., NY, USA, 43–95 (1984).▪ Describes the efficacy of pralatrexate in animal models and the superiority of pralatrexate over methotrexate.Google Scholar
22 Sirotnak FM, Degraw JI, Colwell WT, Piper JR. A new analogue of 10-deazaaminopterin with markedly enhanced curative effects against human tumor xenografts in mice. Cancer Chemother. Pharmacol.42(4),313–318 (1998).Crossref, Medline, CAS, Google Scholar
23 Sirotnak FM, Degraw JI, Schmid FA, Goutas LJ, Moccio DM. New folate analogs of the 10-deaza-aminopterin series. Further evidence for markedly increased antitumor efficacy compared with methotrexate in ascitic and solid murine tumor models. Cancer Chemother. Pharmacol.12(1),26–30 (1984).Medline, CAS, Google Scholar
24 Izbicka E, Diaz A, Campos D, Wick M, Steffen R, Saunders M. Differential activity and potential mechanism of action of pralatrexate (PDX) methotrexate, and pemetrexed (Alimta) in human cancer models in vivo and in vitro.Proceedings of AACR–NCI–EORTC International Conference Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications. San Francisco, CA, USA, 22–26 October 2007.Google Scholar
25 Izbicka E, Diaz A, Streeper R et al. Distinct mechanistic activity profile of pralatrexate in comparison to other antifolates in in vitro and in vivo models of human cancers. Cancer Chemother. Pharm.64(5),993–999 (2009).Crossref, Medline, CAS, Google Scholar
26 Venitz J, Brar SS, Pronk GJ et al. Pralatrexate pharmacokinetics with intravenous administration to oncology patients (poster # B211). Presented at: AACR–NCI–EORTC Internation Conference: Molecular Targets and Therapeutics. Boston, MA, USA, 15–19 November 2009.Google Scholar
27 Malik SM, Liu K, Qiang X et al. Folotyn (pralatrexate injection) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma: U.S. Food and Drug Administration drug approval summary. Clin. Cancer Res.16(20),4921–4927 (2010).Crossref, Medline, CAS, Google Scholar
28 FOLOTYN^®, prescribing information/package insert. Allos Therapeutics, USA (2011).Google Scholar
29 Wang ES, O’Connor O, She Y, Zelenetz AD, Sirotnak FM, Moore MA. Activity of a novel anti-folate (PDX, 10-propargyl 10-deazaaminopterin) against human lymphoma is superior to methotrexate and correlates with tumor RFC-1 gene expression. Leuk. Lymphoma44(6),1027–1035 (2003).Crossref, Medline, CAS, Google Scholar
30 Toner LE, Vrhovac R, Smith EA et al. The schedule-dependent effects of the novel antifolate pralatrexate and gemcitabine are superior to methotrexate and cytarabine in models of human non-Hodgkin’s lymphoma. Clin. Cancer Res.12(3 Pt 1),924–932 (2006).Crossref, Medline, CAS, Google Scholar
31 Marchi E, Paoluzzi L, Scotto L et al. Pralatrexate is synergistic with the proteasome inhibitor bortezomib in in vitro and in vivo models of T-cell lymphoid malignancies. Clin. Cancer Res.16(14),3648–3658 (2010).Crossref, Medline, CAS, Google Scholar
32 O’Connor OA, Horwitz S, Hamlin P et al. Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies. J. Clin. Oncol.27(26),4357–4364 (2009).▪▪ Describes the initial Phase I/II study of patients with relapsed/refractory non-Hodgkin’s lymphoma.Crossref, Medline, Google Scholar
33 Mould DR, Sweeney K, Duffull SB et al. A population pharmacokinetic and pharmacodynamic evaluation of pralatrexate in patients with relapsed or refractory non-Hodgkin’s or Hodgkin’s lymphoma. Clin. Pharmacol. Ther.86(2),190–196 (2009).Crossref, Medline, CAS, Google Scholar
34 Horwitz SM, Vose JM, Advani R et al. Pralatrexate and gemcitabine in patients with relapsed or refractory lymphoproliferative malignancies: Phase 1 results. Blood114(22),667 (Abstract 1674) (2009).▪ Describes the data from a Phase I/II study with the combination of pralatrexate and gemcitabine.Crossref, Medline, Google Scholar
35 Foss F, Horwitz SM, Coiffier B et al. Pralatrexate is an effective treatment for relapsed or refractory transformed mycosis fungoides: a subgroup efficacy analysis from the PROPEL Study. Clin. Lymphoma Myeloma Leuk.12(4),238–243 (2012).Crossref, Medline, CAS, Google Scholar
36 Horwitz SM, Kim YH, Foss F et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood119(18),4115–4122 (2012).▪▪ Describes the findings of the dose-finding trial of pralatrexate in relapsed/refractory cutaneous T-cell lymphoma.Crossref, Medline, CAS, Google Scholar

Vol. 9, No. 1

Metrics

Downloaded 129 times

History

Published online 19 December 2012

Published in print January 2013

Information

Keywords

Financial & competing interests disclosure

L Barbarotta is on the speaker’s bureau for Allos and Genentech. F Foss is a consultant for Allos, Celgene, Seattle Genetics and Eisai. F Foss has study grants from Celgene and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download