Outcome in patients with peripheral T-cell lymphoma treated with pralatrexate, single center experience

Abstract

Background: Peripheral T-cell lymphoma (PTCL) accounts for 10-15% of all non-Hodgkin lymphomas. Five-year overall survival is very poor in all subtypes except in ALK positive anaplastic large cell lymphomas (ALCL). Patients in relapsed-refractory (RR) setting, treatment options are very limited, particularly in patients with poor performance or advanced age. Pralatrexate has been shown to improve remission and survival rates in RR PTCL. We aimed to evaluate the response rates, efficacy and adverse event profile of pralatrexate used in RR PTCL in our center. Material and Methods: Patients followed in hematology department of Mersin University with the diagnosis of RRPTCL and treated with pralatrexate were included in study. Their demographical and clinical data were documented. Response to treatment with pralatrexate was evaluated. Results: Median follow up time was 14 months and mean age at diagnosis was 50.6 (±17.9) in totally 11 patients. Patients received median 2 cycles of pralatrexate. Six patients were refractory to treatment while 5 patients achieved at least partial remission. Conclusions: PTCL has the worst prognosis among all types of lymphomas. Cure rates are still low and new therapeutic options are needed.

Keywords

• Non-hodgkin lymphoma
• Peripheral T-cell lymphoma
• pralatrexate

References

1. Bhurani M, Admojo L, Van Der Weyden C, Twigger R, Bazargan A, Quach H, Zimet A, Coyle L, Lindsay J, Radeski D, Hawkes E, Kennedy G, Irving I, Gutta N, Trotman J, Yeung J, Dunlop L, Hua M, Giri P, Yuen S, Panicker S, Moreton S, Khoo L, Scott A, Kipp D, McQuillan A, McCormack C, Dickinson M, Prince HM. Pralatrexate in relapsed/refractory Tcell lymphoma: a retrospective multicenter study. Leuk Lymphoma. 2021 Feb;62(2):330-6. doi: 10.1080/10428194.2020.1827241.
2. Sharma M, Pro B. Bone Marrow Transplantation for Peripheral T-Cell Non-Hodgkins’ Lymphoma in First Remission. Curr Treat Options Oncol. 2015 Jul;16(7):34. doi: 10.1007/s11864-015-0347-3.
3. Horwitz S, O’Connor OA, Pro B, Illidge T, Fanale M, Advani R, et.al.; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30- positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-40. doi: 10.1016/S0140- 6736(18)32984-2.
4. Hong JY, Yoon DH, Yoon SE, Kim SJ, Lee HS, Eom HS, Lee HW, Shin DY, Koh Y, Yoon SS, Jo JC, Kim JS, Kim SJ, Cho SH, Lee WS, Won JH, Kim WS, Suh C. Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis. Sci Rep. 2019 Dec 30;9(1):20302. doi: 10.1038/ s41598-019-56891-0.
5. O’Connor OA, Horwitz S, Hamlin P, Portlock C, Moskowitz CH, Sarasohn D, Neylon E, Mastrella J, Hamelers R, Macgregor-Cortelli B, Patterson M, Seshan VE, Sirotnak F, Fleisher M, Mould DR, Saunders M, Zelenetz AD. 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. 2009 Sep 10;27(26):4357-64. doi: 10.1200/JCO.2008.20.8470.
6. O’Connor OA, Pro B, Pinter-Brown L, Bartlett N, Popplewell L, Coiffier B, Lechowicz MJ, Savage KJ, Shustov AR, Gisselbrecht C, Jacobsen E, Zinzani PL, Furman R, Goy A, Haioun C, Crump M, Zain JM, Hsi E, Boyd A, Horwitz S. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011 Mar 20;29(9):1182-9. doi: 10.1200/JCO.2010.29.9024.
7. Advani RH, Ansell SM, Lechowicz MJ, Beaven AW, Loberiza F, Carson KR, Evens AM, Foss F, Horwitz S, Pro B, Pinter-Brown LC, Smith SM, Shustov AR, Savage KJ, Vose JM. A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial. Br J Haematol. 2016 Feb;172(4):535-44. doi: 10.1111/bjh.13855.
8. Mak V, Hamm J, Chhanabhai M, Shenkier T, Klasa R, Sehn LH, Villa D, Gascoyne RD, Connors JM, Savage KJ. Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors. J Clin Oncol. 2013 Jun 1;31(16):1970-6. doi: 10.1200/JCO.2012.44.7524.

9. Biasoli I, Cesaretti M, Bellei M, Maiorana A, Bonacorsi G, Quaresima M, Salati M, Federico M, Luminari S. Dismal outcome of T-cell lymphoma patients failing first-line treatment: results of a population-based study from the Modena Cancer Registry. Hematol Oncol. 2015 Sep;33(3):147-51. doi: 10.1002/hon.2144.
10. Hong X, Song Y, Huang H, Bai B, Zhang H, Ke X, Shi Y, Zhu J, Lu G, Liebscher S, Cai C. Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study. Target Oncol. 2019 Apr;14(2):149-58. doi: 10.1007/s11523-019- 00630-y.
11. Maruyama D, Nagai H, Maeda Y, Nakane T, Shimoyama T, Nakazato T, Sakai R, Ishikawa T, Izutsu K, Ueda R, Tobinai K. Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. Cancer Sci. 2017 Oct;108(10):2061-8. doi: 10.1111/cas.13340.
12. Amengual JE, Lichtenstein R, Lue J, Sawas A, Deng C, Lichtenstein E, Khan K, Atkins L, Rada A, Kim HA, Chiuzan C, Kalac M, Marchi E, Falchi L, Francescone MA, Schwartz L, Cremers S, O’Connor OA. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood. 2018 Jan 25;131(4):397-407. doi: 10.1182/ blood-2017-09-806737.
13. Lee SS, Jung SH, Ahn JS, Kim YK, Cho MS, Jung SY, Lee JJ, Kim HJ, Yang DH. Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients. J Korean Med Sci. 2016 Jul;31(7):1160-3. doi: 10.3346/jkms.2016.31.7.1160.
14. Toner LE, Vrhovac R, Smith EA, Gardner J, Heaney M, Gonen M, Teruya-Feldstein J, Sirotnak F, O’Connor OA. The schedule-dependent effects of the novel antifolate pralatrexate and gemcitabine are superior to methotrexate and cytarabine in models of human nonHodgkin’s lymphoma. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):924- 32. doi: 10.1158/1078- 0432.CCR-05-0331.
15. Zhu J, Yeoh EM, Maeda Y, Tobinai K. Efficacy and safety of single-agent pralatrexate for treatment of angioimmunoblastic T-cell lymphoma after failure of first line therapy: a pooled analysis. Leuk Lymphoma.2020 Sep;61(9):2145-52. doi: 10.1080/10428194.2020.1765232.
16. Hong JY, Yoon DH, Yoon SE, Kim SJ, Lee HS, Eom HS, Lee HW, Shin DY, Koh Y, Yoon SS, Jo JC, Kim JS, Kim SJ, Cho SH, Lee WS, Won JH, Kim WS, Suh C. Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis. Sci Rep. 2019 Dec 30;9(1):20302. doi: 10.1038/s41598-019-56891-0.