Periferik T cell Lenfomalı Hastalarda Belinostat Deneyimi; Çok Merkezli Gerçek Yaşam Verisi, Türkiye

Yıl 2022, Cilt: 44 Sayı: 4, 454 - 459, 19.07.2022

Aydan Akdeniz Fatma Keklik Karadağ Figen Atalay Burak Deveci Mine Miskioğlu Pelin Aytan Guray Saydam

https://doi.org/10.20515/otd.1038937

Öz

Periferik T hücreli lenfomalar (PTHL) non hodgkin lenfomaların oldukça agresif nadir bir alt türüdür. ALK-pozitif anaplastik büyük hücreli lenfoma dışındaki tüm alt gruplarda prognoz kötüdür. Son yıllarda kurtarma rejimlerinin yanı sıra relaps refrakter (RR) hastalarda hedef tedavilerin kullanımı giderek yaygınlaşmaktadır. Bunlardan belinostat; histon deasetilaz (HDAC) inhibitörü olup Türkiye’de Temmuz 2019 dan itibaren RR PTHL hastalarda kullanıma girmiştir. Bu çalışmada şimdiye kadar RR PTHL tanısı ile ülkemizde belinostat tedavisi alan hastaların sonuçlarının değerlendirilmesi planlandı. Kullanıma girdiği tarihten itibaren RR PTHL ile tanısı olan ve Türkiyede belinostat tedavisi alan ve erişilebilen tüm hastalar çalışmaya dahil edildi. Demografik, patolojik ve klinik özellikleri, objektif yanıt oranları kaydedildi. Elde edilen veriler literatür eşliğinde değerlendirildi. Toplam 5 merkezden 10 hasta değerlendirildi. Tanıdan itibaren takip süresi 38 ay idi. En sık görülen patolojik alt tip ALK negatif PTHL (%40) idi. Belinostat tedavisi ile 2 hastada tam yanıt, 3 hastada parsiyel yanıt, 4 hastada da progresyon izlendi, 1 hastada ise durum değerlendirilmesi yapılamadı. Takiplerinde progrese olan 2 hasta eksitus oldu. Bu hastalarda belinostattan ölüme kadar geçen süre 1 ve 2 ay idi. Bir hastada grade 3 hematolojik yan etki (nötropeni) görüldü. Çalışmamız belinostat ile ilgili olarak ülkemizde ulusal çok merkezli gerçek yaşam verilerini sunan ilk çalışma olması bakımından önem taşımaktadır

Anahtar Kelimeler

Periferik T cell lenfoma, Belinostat, non hodgki n lenfoma

Destekleyen Kurum

yok

Outcome of Belinostat in Patients with Peripheral T Cell Lymphoma, Multicenter Real-Life Data, Turkey

Öz

T-cell lymphoma (PTHL) is a rare and aggressive subtype of non-Hodgkin lymphomas. The prognosis is poor in all subgroups except for ALK-positive anaplastic large cell lymphoma. In recent years, the use of targeted therapies in patients with relapse-refractory (RR) disease, as well as salvage chemotherapy regimens, has become increasingly common. Among these, belinostat, a histone deacetylase (HDAC) inhibitor has been used in patients with RR PTHL since July 2019 in Turkey.In this study, it was aimed to evaluate the outcome of patients who were known to be treated with belinostat in Turkey with the diagnosis of RR PTHL. Patients who were diagnosed with RR PTHL and known to be treated with belinostat in Turkey since the date of approval for its use were included in the study. Demographic, pathological and clinical features and objective response rates were recorded. The data obtained were evaluated in the light of the literature. Ten patients from a total of 5 centers were evaluated. The follow-up period from diagnosis was 38 months. The most common pathological subtype was ALK-negative PTHL (40%). Complete response in 2 patients, partial response in 3 patients and progression in 4 patients were observed with belinostat, and the response status could not be evaluated in 1 patient. Two patients who progressed on belinostat treatment died. Time from belinostat to death in these patients was 1 and 2 months, respectively. Grade 3 hematological side effects (neutropenia) were observed in one patient. Our study is important in terms of the fact that it is the first study in Turkey to present national multicenter real-life data regarding belinostat.

Anahtar Kelimeler

Peripheral T cell lymphoma, Peripheral T cell lymphoma, Belinostat, non hodgkin

Kaynakça

• Referans1-Ma H, Cheng B, Falchi L, et al. Survival benefit in patients with peripheral T-cell lymphomas after treatments with novel therapies and clinical trials. Hematol Oncol. 2020 Feb;38(1):51–8.
• Referans2-Yoon SE, Song Y, Kim SJ, et al. Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia. Lancet Reg Health West Pac. 2021 Mar 22;10:100126
• Referans3- Ellin F, Landström J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014 Sep;124(10):1570–7.
• Referans4- Maeda Y, Nishimori H, Yoshida I, et al. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017 Dec;102(12):2097–103
• Referans5- Wulf GG, Altmann B, Ziepert M, et al.; ACT-2 study investigators. Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial. Leukemia. 2021 Jan;35(1):143–55.
• Referans6- Gleeson M, Peckitt C, To YM, et al. CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial. Lancet Haematol. 2018 May;5(5):e190–200
• Referans7- Horwitz S, O’Connor OA, Pro B, 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 [Erratum in: Lancet. 2019 Jan 19;393] [10168] [:228. PMID: 30522922; PMCID: PMC6436818]. Lancet. 2019 Jan;393(10168):229–40.
• Referans8- Li X, Cui Y, Sun Z, et al. DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China. Clin Cancer Res. 2016 Nov;22(21):5223–8.
• Referans9- Skamene T, Crump M, Savage KJ, et al. Salvage chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: a subset analysis of the Canadian Cancer Trials Group LY.12 randomized phase 3 study. Leuk Lymphoma. 2017 Oct;58(10):2319–27.
• Referans10- Kogure Y, Yoshimi A, Ueda K, et al. Modified ESHAP regimen for relapsed/refractory T cell lymphoma: a retrospective analysis. Ann Hematol. 2015 Jun;94(6):989–94.
• Referans11- Zelenetz AD, Hamlin P, Kewalramani T, et al. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2003;14 Suppl 1:i5–10.
• Referans12- 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. 2012 Feb;30(6):631–6.
• Referans13- 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. 2011 Mar;29(9):1182–9.
• Referans14- O’Connor OA, Horwitz S, Masszi T, et al. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015 Aug;33(23):2492–9.
• Referans15- Horwitz SM, Advani RH, Bartlett NL, et al. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014 May;123(20):3095–100.
• Referans16- Foss F, Advani R, Duvic M, et al. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015 Mar;168(6):811–9.
• Referans17- Bachy E, Camus V, Thieblemont C, et al. Final analysis of the Ro-CHOP Phase III (conducted by LYSA): Romidepsin plus CHOP in patients with peripheral T-cell lymphoma. Presented at: 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5–9, 2020. Abstract 39
• Referans18- Johnston PB, Cashen AF, Nikolinakos PG, Beaven AW, Barta SK, Bhat G, et al. Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma. Exp Hematol Oncol. 2021 Feb;10(1):15.
• Referans19- Qi F, Dong M, He X, Li Y, Wang W, Liu P, et al. Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified. Ann Hematol. 2017 Feb;96(2):245–51.
• Referans20- Campbell P, Thomas CM. Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. J Oncol Pharm Pract. 2017 Mar;23(2):143–7.