R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey

Öz:

Objective: The introduction of rituximab significantly improved the response rates of patients with diffuse large B-cell lymphoma (DLBCL). The rituximab biosimilar Redditux® (RED) was approved in Turkey for all indications of the reference molecule MabThera® (MBT) in March 2018. The aim of this retrospective analysis was to evaluate the efficacy and safety of RED in de novo DLBCL. Method: All patients diagnosed with DLBCL (n = 54) according to the World Health Organization criteria and followed up at the Hematology Division of İstanbul University, İstanbul Medical Faculty, from February 2019 to February 2020 were included in our analysis. Results: Median age of the patients was 59 years (range: 17-79) and 57% of the patients were males. Median follow-up time was 10 months (range: 4-15). The overall response rate at the end of the treatment protocol was 86%, with 37 complete responses and 8 partial responses. The 12-month estimated overall survival was 76.8% [95% confidence interval (CI): 0.54-0.89] and the progression free survival was 78.5% (95% CI: 0.59 - 0.89). Adverse events were reported in 53% (n = 29) of the patients. The most common adverse event was grade 2 infusion reactions. There was no serious adverse event that instigated the cessation of the drug. Seven patients died during the follow-up due to central nervous system disease (n = 3), progressive disease (n = 2), and unknown causes (n = 2). Conclusion: Compared to the initial historical trial of MBT, the complete response in stage 2, 3, and 4 patients seem to be slightly lower (69% vs. 75%), although the overall response rates are quite similar (86% vs. 82%). However, large prospective controlled studies and more real-life data with longer follow-up are needed to document the non-inferiority and safety of RED compared to MBT.

Anahtar Kelime:

Biobenzer Rituksimab (Redditux®) İçeren R-CHOP Kemoterapisinin Yeni Tanı Diffüz Büyük B-hücreli Lenfoma Hastalarında Sonuçları: Türkiye’den Tek Merkez Gerçek Yaşam Verileri İlk Ön Sonuçları

Öz:

Amaç: Kimerik anti-CD20 insan immünoglobulin G1 monoklonal antikoru rituksimabın kullanıma girmesiyle B-hücreli lenfoproliferatif hastalıklarda yanıt oranları anlamlı derecede artmıştır. Biyobenzerler, Kabul edilmiş biyolojik moleküllere güvenirlik, saflık ve etki açısından yüksek oranda benzerlik gösteren biyolojik ürünlerdir. Biyobenzer Redditux® (RED), Mart 2018’de Türkiye’de, MabThera® (MBT) kullanılan tüm endikasyonlar için kullanım onayı aldı. Kurumumuzda, Şubat 2019’dan beri hematolojik hastalıklarda biyobenzer RED kullanıma girmiştir. Geriye dönük çalışmamızın amacı, yeni tanı DBBHL olgularında RED’in etkinliğini ve güvenirliğini değerlendirmektir. Yöntem: DBBHL tanısı almış tüm hastalarda (n = 54) Dünya Sağlık Örgütü tanı kriterleri kullanılmış ve İstanbul Üniversitesi, İstanbul Tıp Fakültesi İç Hastalıkları Kliniği, Hematoloji Bölümü'nde, Şubat 2019 ile Şubat 2020 arasında tanı ve tedavi almışlardır. Bulgular: Median yaş 59 (aralık: 17-79) olup olgularımızın %57’si erkektir. Ortalama takip süremiz 10 aydır (aralık: 4-15 ay). Tedavi protokolü sonunda genel yanıt oranı %86 olup, 37 hastada tam yanıt ve 8 hastada kısmi yanıt elde edilmiştir. Evre 2-4 olgularda genel yanıt oranı benzerdir (%86). On iki aylık genel sağkalım %76,8 [%95 güven aralığı (GA): 0,54 - 0,89] ve progresyonsuz sağkalım %78,5 (%95 GA: 0,59 - 0,89) olarak tespit edilmiştir. Yan etkiler olguların %53’ünde tespit edilmiştir (n=29). En sık yan etki derece 2 infüzyon reaksiyonlarıdır. İlacın kesilmesini gerektiren herhangi bir ciddi yan etki gözlenmemiştir. Üç hasta merkezi sinir sistemi hastalığına, 2 hasta ilerleyici hastalığa ve 2 hasta tespit edilemeyen nedenlerle olmak üzere toplam 7 hasta kaybedilmiştir. Sonuç: MBT’nin ilk orjinal makalesi ile karşılaştırdığımızda, evre 2-4 olgularda yanıt oranımız biraz düşük (%69 vs %75) olmakla birlikte genel yanıt oranlarımız (%86 vs %82) benzerdir. Geniş prospektif kontrollü çalışmalara ve uzun takip süreli daha fazla gerçek yaşam verisine, RED’nin MBT’ye benzer etki ve güvenirliği olduğunu gösterebilmek için ihtiyaç vardır.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-42. doi: 10.1056/NEJMoa011795.
2. U.S.Food&DrugAdministration. Biosimilars Available from: https://www. fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars.
3. Muller R, Renner C, Gabay C, Cassata G, Lohri A, Hasler P. The advent of biosimilars: challenges and risks. Swiss Med Wkly. 2014;144:w13980. doi: 10.4414/smw.2014.13980.
4. Niederwieser D, Schmitz S. Biosimilar agents in oncology/haematology: from approval to practice. Eur J Haematol. 2011;86:277-88. doi: 10.1111/j.1600-0609.2010.01566.x.
5. Swerdlow SH CE, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
6. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: cotswolds meeting. J Clin Oncol. 1989;7:1630-6. doi: 10.1200/ JCO.1989.7.11.1630.
7. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649- 55.
8. Pfreundschuh M, Ho AD, Cavallin-Stahl E, et al. Prognostic significance of maximum tumour (bulk) diameter in young patients with goodprognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol. 2008;9:435-44.
9. Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v116-25. doi: 10.1093/ annonc/mdv304.
10. Roy PS, John S, Karankal S, et al. Comparison of the efficacy and safety of Rituximab (Mabthera) and its biosimilar (Reditux) in diffuse large B-cell lymphoma patients treated with chemo-immunotherapy: A retrospective analysis. Indian J Med Paediatr Oncol. 2013;34:292-8. doi: 10.4103/0971-5851.125248.
11. Bankar A, Korula A, Abraham A, et al. Comparison of the efficacy of innovator rituximab and its biosimilars in diffuse large b cell lymphoma patients: a retrospective analysis. Indian J Hematol Blood Transfus. 2020;36:71-7. doi: 10.1007/s12288-019-01167-w.
12. Viswabandya A, Shah S, Mukhopadhyay A, et al. Randomized, doubleblind, pharmacokinetic equivalence trial comparing drl-rituximab with mabthera in patients with diffuse large b-cell lymphoma. J Glob Oncol. 2019;5:1-13. doi: 10.1200/JGO.19.00248.
13. Shi Y, Song Y, Qin Y, et al. A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. J Hematol Oncol. 2020;13:38. doi: 10.1186/s13045-020-00871-9.
14. Candelaria M, Gonzalez DE, Delamain MT, et al. Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study. Leuk Lymphoma. 2019;60:3375-85. doi: 10.1080/10428194.2019.1633632.
15. Lee K, Ha JY, Jung AR, et al. The clinical outcomes of rituximab biosimilar CT-P10 (Truxima((R))) with CHOP as first-line treatment for patients with diffuse large B-cell lymphoma: real-world experience. Leuk Lymphoma. 2020;61:1575-83. doi: 10.1080/10428194.2020.1742906.
16. Ganesan P, Sagar TG, Kannan K, et al. Long-term outcome of diffuse large B-cell lymphoma: Impact of biosimilar rituximab and radiation. Indian J Cancer. 2017;54:430-5. doi: 10.4103/ijc.IJC_241_17.
17. Mounie M, Costa N, Conte C, et al. Real-world costs of illness of Hodgkin and the main B-Cell Non-Hodgkin lymphomas in France. J Med Econ. 2020;23:235-42. doi: 10.1080/13696998.2019.1702990.

APA	Ozbalak M, Mastanzade M, Özlük D, tiryaki t, PINAR OZBALAK E, Yonal-Hindilerden I, ALTAY A, Yegen G, Yenerel M, Nalcaci M, Kalayoglu Besisik S (2021). R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. , 194 - 198. 10.4274/iksstd.2021.35761
Chicago	Ozbalak Murat,Mastanzade Metban,Özlük Dilek Özden,tiryaki tarık onur,PINAR OZBALAK EZGI,Yonal-Hindilerden Ipek,ALTAY Ali Yılmaz,Yegen Gulcin,Yenerel Mustafa Nuri,Nalcaci Meliha,Kalayoglu Besisik Sevgi R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. (2021): 194 - 198. 10.4274/iksstd.2021.35761
MLA	Ozbalak Murat,Mastanzade Metban,Özlük Dilek Özden,tiryaki tarık onur,PINAR OZBALAK EZGI,Yonal-Hindilerden Ipek,ALTAY Ali Yılmaz,Yegen Gulcin,Yenerel Mustafa Nuri,Nalcaci Meliha,Kalayoglu Besisik Sevgi R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. , 2021, ss.194 - 198. 10.4274/iksstd.2021.35761
AMA	Ozbalak M,Mastanzade M,Özlük D,tiryaki t,PINAR OZBALAK E,Yonal-Hindilerden I,ALTAY A,Yegen G,Yenerel M,Nalcaci M,Kalayoglu Besisik S R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. . 2021; 194 - 198. 10.4274/iksstd.2021.35761
Vancouver	Ozbalak M,Mastanzade M,Özlük D,tiryaki t,PINAR OZBALAK E,Yonal-Hindilerden I,ALTAY A,Yegen G,Yenerel M,Nalcaci M,Kalayoglu Besisik S R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. . 2021; 194 - 198. 10.4274/iksstd.2021.35761
IEEE	Ozbalak M,Mastanzade M,Özlük D,tiryaki t,PINAR OZBALAK E,Yonal-Hindilerden I,ALTAY A,Yegen G,Yenerel M,Nalcaci M,Kalayoglu Besisik S "R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey." , ss.194 - 198, 2021. 10.4274/iksstd.2021.35761
ISNAD	Ozbalak, Murat vd. "R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey". (2021), 194-198. https://doi.org/10.4274/iksstd.2021.35761

APA	Ozbalak M, Mastanzade M, Özlük D, tiryaki t, PINAR OZBALAK E, Yonal-Hindilerden I, ALTAY A, Yegen G, Yenerel M, Nalcaci M, Kalayoglu Besisik S (2021). R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. İstanbul Kanuni Sultan Süleyman Tıp Dergisi, 13(3), 194 - 198. 10.4274/iksstd.2021.35761
Chicago	Ozbalak Murat,Mastanzade Metban,Özlük Dilek Özden,tiryaki tarık onur,PINAR OZBALAK EZGI,Yonal-Hindilerden Ipek,ALTAY Ali Yılmaz,Yegen Gulcin,Yenerel Mustafa Nuri,Nalcaci Meliha,Kalayoglu Besisik Sevgi R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. İstanbul Kanuni Sultan Süleyman Tıp Dergisi 13, no.3 (2021): 194 - 198. 10.4274/iksstd.2021.35761
MLA	Ozbalak Murat,Mastanzade Metban,Özlük Dilek Özden,tiryaki tarık onur,PINAR OZBALAK EZGI,Yonal-Hindilerden Ipek,ALTAY Ali Yılmaz,Yegen Gulcin,Yenerel Mustafa Nuri,Nalcaci Meliha,Kalayoglu Besisik Sevgi R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. İstanbul Kanuni Sultan Süleyman Tıp Dergisi, vol.13, no.3, 2021, ss.194 - 198. 10.4274/iksstd.2021.35761
AMA	Ozbalak M,Mastanzade M,Özlük D,tiryaki t,PINAR OZBALAK E,Yonal-Hindilerden I,ALTAY A,Yegen G,Yenerel M,Nalcaci M,Kalayoglu Besisik S R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. İstanbul Kanuni Sultan Süleyman Tıp Dergisi. 2021; 13(3): 194 - 198. 10.4274/iksstd.2021.35761
Vancouver	Ozbalak M,Mastanzade M,Özlük D,tiryaki t,PINAR OZBALAK E,Yonal-Hindilerden I,ALTAY A,Yegen G,Yenerel M,Nalcaci M,Kalayoglu Besisik S R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey. İstanbul Kanuni Sultan Süleyman Tıp Dergisi. 2021; 13(3): 194 - 198. 10.4274/iksstd.2021.35761
IEEE	Ozbalak M,Mastanzade M,Özlük D,tiryaki t,PINAR OZBALAK E,Yonal-Hindilerden I,ALTAY A,Yegen G,Yenerel M,Nalcaci M,Kalayoglu Besisik S "R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey." İstanbul Kanuni Sultan Süleyman Tıp Dergisi, 13, ss.194 - 198, 2021. 10.4274/iksstd.2021.35761
ISNAD	Ozbalak, Murat vd. "R-CHOP Chemotherapy with a Rituximab Biosimilar (Redditux®) for Patients with de novo Diffuse Large B-cell Lymphoma: First Preliminary Results of a RealLife Single-Center Experience from Turkey". İstanbul Kanuni Sultan Süleyman Tıp Dergisi 13/3 (2021), 194-198. https://doi.org/10.4274/iksstd.2021.35761