Yıl: 2021 Cilt: 38 Sayı: 3 Sayfa Aralığı: 211 - 217 Metin Dili: İngilizce DOI: 10.4274/tjh.galenos.2021.2020.0555 İndeks Tarihi: 25-05-2022

Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients

Öz:
Objective: Constantly increasing health expenditures lead to the use of generic molecules and generic versions of bortezomib have been used for a long time. The aim of this study is to retrospectively examine the effectiveness, side effects, and reliability of generic bortezomib in newly diagnosed multiple myeloma (MM) patients. Materials and Methods: The data of 95 patients who received four cycles of bortezomib as first- or second-line therapy in a single center were retrospectively recorded. Treatment responses, side effects, and progression-free survival (PFS) rates were calculated and compared. Results: Of the 95 patients, 42 used the original and 53 used the generic molecule. Epidemiological data, MM types, genetic risk groups, laboratory values at diagnosis, and bortezomib treatment lines (as a first line or second) were evaluated and there was no statistical difference between the two groups. When the response rates were evaluated according to International Myeloma Working Group criteria, there was no significant difference (p=0.42). Rates of partial response and higher responses were similar (81% vs. 79.2%, p=0.84). PFS rates were 42.8 months with the original and 37.8 months with the generic molecule (p=0.68). Side effects were seen in 44.2% of all patients, and the most common side effects were neuropathy, cytopenia, and infection. These rates were similar in the two groups (p=0.55). Conclusion: Although this retrospective study is limited in scope, it is the first study comparing the original molecule of bortezomib with a generic version. There were no statistical differences between the two groups in terms of treatment responses, PFS, or side effects. However, large-scale evaluations will help obtain more data on this subjec
Anahtar Kelime:

Yeni Tanı Multipl Myelom Hastalarında Eşdeğer Bortezomib Molekülünün Değerlendirilmesi

Öz:
Amaç: Sürekli artan sağlık harcamaları jenerik moleküllerin kullanımına yol açmaktadır ve bortezomibin jenerik molekülleri uzun süredir kullanılmaktadır. Bu çalışmanın amacı, yeni tanı konmuş multipl myelom (MM) hastalarında jenerik bortezomibin etkinliğini, yan etkilerini ve güvenilirliğini retrospektif olarak incelemektir. Gereç ve Yöntemler: Tek merkezli çalışmamızda birinci veya ikinci basamak tedavide dört kür bortezomib alan 95 hastanın verileri geriye dönük olarak incelendi. Tedavi yanıtları, yan etkiler ve progresyonsuz sağkalım (PFS) oranları hesaplandı ve karşılaştırıldı. Bulgular: Doksan beş hastanın 42’si orijinal molekülü, 53’ü eşdeğer molekülü kullanmıştır. Epidemiyolojik veriler, MM tipleri, genetik risk grupları, tanı anındaki laboratuvar değerleri ve bortezomib tedavi sıraları (birinci sıra veya ikinci sıra olarak) değerlendirildiğinde iki grup arasında istatistiksel fark olmadığı izlendi. Uluslararası Myelom Çalışma Grubu kriterlerine göre yanıt oranları değerlendirildiğinde anlamlı bir fark bulunmadı (p=0,42). Kısmi yanıt ve daha yüksek yanıt oranları benzerdi (%81’e karşı %79,2, p=0,84). PFS süreleri orijinal molekül için 42,8 ay ve eşdeğer molekül için 37,8 ay olarak hesaplandı (p=0,68). Yan etkiler tüm hastaların %44,2’sinde görüldü ve en sık görülen yan etkiler nöropati, sitopeni ve enfeksiyondu. Bu yan etkilerin görülme oranları iki grupta benzerdi (p=0,55). Sonuç: Bu retrospektif çalışma, kapsamı sınırlı olmakla birlikte, orijinal bortezomib molekülünü eşdeğeri ile karşılaştıran ilk çalışmadır. Tedavi yanıtları, PFS veya yan etkiler açısından iki grup arasında istatistiksel fark izlenmemiştir. Ancak geniş çaplı değerlendirmeler bu konuda daha fazla veri elde edilmesine yardımcı olacaktır.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.
  • 2. Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin 2016;66:443-459.
  • 3. Cowan AJ, Allen C, Barac A, Basaleem H, Bensenor I, Curado MP, Foreman K, Gupta R, Harvey J, Hosgood HD, Jakovljevic M, Khader Y, Linn S, Lad D, Mantovani L, Nong VM, Mokdad A, Naghavi M, Postma M, Roshandel G, Shackelford K, Sisay M, Nguyen CT, Tran TT, Xuan BT, Ukwaja KN, Vollset SE, Weiderpass E, Libby EN, Fitzmaurice C. Global burden of multiple myeloma: a systematic analysis for the Global Burden of Disease Study 2016. JAMA Oncol 2018;4:1221-1227.
  • 4. Field-Smith A, Morgan GJ, Davies FE. Bortezomib (Velcadetrade mark) in the treatment of multiple myeloma. Ther Clin Risk Manag 2006;2:271-279.
  • 5. Jackson G, Einsele H, Moreau P, Miguel JS. Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies. Cancer Treat Rev 2005;31:591-602.
  • 6. Richardson PG, Mitsiades C, Hideshima T, Anderson KC. Proteasome inhibition in the treatment of cancer. Cell Cycle 2005;4:290-296.
  • 7. Mateos MV, Ludwig H, Bazarbachi A, Beksac M, Bladé J, Boccadoro M, Cavo M, Delforge M, Dimopoulos MA, Facon T, Geraldes C, Goldschmidt H, Hájek R, Hansson M, Jamroziak K, Leiba M, Masszi T, Mendeleeva L, O’Dwyer M, Plesner T, San-Miguel JF, Straka C, van de Donk NWCJ, Yong K, Zver S, Moreau P, Sonneveld P. Insights on multiple myeloma treatment strategies. Hemasphere 2018;3:e163.
  • 8. Borcade Drug Information. Available online at https://www.ndrugs. com/?s=borcade.
  • 9. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538- 548.
  • 10. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Washington, HHS, 2017. Available online at https://ctep.cancer.gov/protocoldevelopment/ electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf
  • 11. Eskazan AE, Soysal T. The tolerability issue of generic imatinib in patients with chronic myeloid leukemia (Comment on Adi J. Klil-Drori et al., Haematologica 2019;104(7):e293). Haematologica 2019;104:e330.
  • 12. Lejniece S, Udre I, Rivkina A. Generic imatinib in the treatment of chronic myeloid leukemia: two years’ experience in Latvia. Exp Oncol 2017;39:151- 154.
  • 13. Kanavos P. Do generics offer significant savings to the UK National Health Service? Curr Med Res Opin 2007;23:105-116.
  • 14. Gallelli L, Palleria C, De Vuono A, Mumoli L, Vasapollo P, Piro B, Russo E. Safety and efficacy of generic drugs with respect to brand formulation. J Pharmacol Pharmacother 2013;4(Suppl 1):S110-114.
  • 15. Borgheini G. The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs. Clin Ther 2003;25:1578-1592.
  • 16. Fareed J, Leong WL, Hoppensteadt DA, Jeske WP, Walenga J, Wahi R, Bick RL. Generic low-molecular-weight heparins: some practical considerations. Semin Thromb Hemost 2004;30:703-713.
  • 17. Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M, Dechow T, Kröger N, Salwender H, Metzner B, Sezer O, Engelhardt M, Wolf HH, Einsele H, Volpert S, Heinecke A, Berdel WE, Kienast J; Deutsche Studiengruppe Multiples Myelom. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 2007;138:330-337.
  • 18. Kim SJ, Kim J, Cho Y, Seo BK, Kim BS. Combination chemotherapy with bortezomib, cyclophosphamide and dexamethasone may be effective for plasma cell leukemia. Jpn J Clin Oncol 2007;37:382-384.
  • 19. Davies FE, Wu P, Jenner M, Srikanth M, Saso R, Morgan GJ. The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Haematologica 2007;92:1149-1150.
  • 20. Tsukada N, Ikeda M, Shingaki S, Miyazaki K, Meshitsuka S, Yoshiki Y, Abe Y, Suzuki K. Induction treatment with bortezomib-cyclophosphamide- dexamethasone (CyBorD) for newly diagnosed transplant-eligible patients with multiple myeloma. Rinsho Ketsueki 2015;56:1069-1075.
  • 21. Tanaka K, Toyota S, Akiyama M, Wakimoto N, Nakamura Y, Najima Y, Doki N, Kakihana K, Igarashi A, Kobayashi T, Ohashi K, Kudo D, Shinagawa A, Takano H, Fujio T, Okoshi Y, Hori M, Kumagai T, Saito T, Mukae J, Yamamoto K, Tsutsumi I, Komeno T, Yoshida C, Yamamoto M, Kojima H; on behalf of the Ochanomizu Hematology Study Group. Efficacy and safety of a weekly cyclophosphamide-bortezomib-dexamethasone regimen as induction therapy prior to autologous stem cell transplantation in Japanese patients with newly diagnosed multiple myeloma: a phase 2 multicenter trial. Acta Haematol 2019;141:111-118.
  • 22. Khan ML, Reeder CB, Kumar SK, Lacy MQ, Reece DE, Dispenzieri A, Gertz MA, Greipp P, Hayman S, Zeldenhurst S, Dingli D, Lust J, Russell S, Laumann KM, Mikhael JR, Bergsagel PL, Fonseca R, Rajkumar SV, Stewart AK. A comparison of lenalidomide/dexamethasone versus cyclophosphamide/lenalidomide/ dexamethasone versus cyclophosphamide/bortezomib/dexamethasone in newly diagnosed multiple myeloma. Br J Haematol 2012;156:326-333.
  • 23. Figueiredo A, Atkins H, Mallick R, Kekre N, Kew A, McCurdy A. Cyclophosphamide-bortezomib-dexamethasone compared with bortezomib-dexamethasone in transplantation-eligible patients with newly diagnosed multiple myeloma. Curr Oncol 2020;27:e81-e85.
  • 24. Ashrafi F, Moghaddas A, Darakhshandeh A. Reduced weekly subcutaneous doses of bortezomib in combination with cyclophosphamide and dexamethasone for newly diagnosed multiple myeloma. J Res Pharm Pract 2020;9:56-59.
APA MERSİN S, GEDÜK A, MEHTAP Ö, Tarkun P, Ünal S, Polat M, AYGÜN K, YENİHAYAT E, ALBAYRAK H, Hacıhanefioğlu A (2021). Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. , 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
Chicago MERSİN Sinan,GEDÜK Ayfer,MEHTAP Özgür,Tarkun Pinar,Ünal Serkan,Polat Merve Gökçen,AYGÜN Kemal,YENİHAYAT Emel Merve,ALBAYRAK Hayrunnisa,Hacıhanefioğlu Abdullah Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. (2021): 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
MLA MERSİN Sinan,GEDÜK Ayfer,MEHTAP Özgür,Tarkun Pinar,Ünal Serkan,Polat Merve Gökçen,AYGÜN Kemal,YENİHAYAT Emel Merve,ALBAYRAK Hayrunnisa,Hacıhanefioğlu Abdullah Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. , 2021, ss.211 - 217. 10.4274/tjh.galenos.2021.2020.0555
AMA MERSİN S,GEDÜK A,MEHTAP Ö,Tarkun P,Ünal S,Polat M,AYGÜN K,YENİHAYAT E,ALBAYRAK H,Hacıhanefioğlu A Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. . 2021; 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
Vancouver MERSİN S,GEDÜK A,MEHTAP Ö,Tarkun P,Ünal S,Polat M,AYGÜN K,YENİHAYAT E,ALBAYRAK H,Hacıhanefioğlu A Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. . 2021; 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
IEEE MERSİN S,GEDÜK A,MEHTAP Ö,Tarkun P,Ünal S,Polat M,AYGÜN K,YENİHAYAT E,ALBAYRAK H,Hacıhanefioğlu A "Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients." , ss.211 - 217, 2021. 10.4274/tjh.galenos.2021.2020.0555
ISNAD MERSİN, Sinan vd. "Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients". (2021), 211-217. https://doi.org/10.4274/tjh.galenos.2021.2020.0555
APA MERSİN S, GEDÜK A, MEHTAP Ö, Tarkun P, Ünal S, Polat M, AYGÜN K, YENİHAYAT E, ALBAYRAK H, Hacıhanefioğlu A (2021). Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. Turkish Journal of Hematology, 38(3), 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
Chicago MERSİN Sinan,GEDÜK Ayfer,MEHTAP Özgür,Tarkun Pinar,Ünal Serkan,Polat Merve Gökçen,AYGÜN Kemal,YENİHAYAT Emel Merve,ALBAYRAK Hayrunnisa,Hacıhanefioğlu Abdullah Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. Turkish Journal of Hematology 38, no.3 (2021): 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
MLA MERSİN Sinan,GEDÜK Ayfer,MEHTAP Özgür,Tarkun Pinar,Ünal Serkan,Polat Merve Gökçen,AYGÜN Kemal,YENİHAYAT Emel Merve,ALBAYRAK Hayrunnisa,Hacıhanefioğlu Abdullah Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. Turkish Journal of Hematology, vol.38, no.3, 2021, ss.211 - 217. 10.4274/tjh.galenos.2021.2020.0555
AMA MERSİN S,GEDÜK A,MEHTAP Ö,Tarkun P,Ünal S,Polat M,AYGÜN K,YENİHAYAT E,ALBAYRAK H,Hacıhanefioğlu A Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. Turkish Journal of Hematology. 2021; 38(3): 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
Vancouver MERSİN S,GEDÜK A,MEHTAP Ö,Tarkun P,Ünal S,Polat M,AYGÜN K,YENİHAYAT E,ALBAYRAK H,Hacıhanefioğlu A Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients. Turkish Journal of Hematology. 2021; 38(3): 211 - 217. 10.4274/tjh.galenos.2021.2020.0555
IEEE MERSİN S,GEDÜK A,MEHTAP Ö,Tarkun P,Ünal S,Polat M,AYGÜN K,YENİHAYAT E,ALBAYRAK H,Hacıhanefioğlu A "Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients." Turkish Journal of Hematology, 38, ss.211 - 217, 2021. 10.4274/tjh.galenos.2021.2020.0555
ISNAD MERSİN, Sinan vd. "Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients". Turkish Journal of Hematology 38/3 (2021), 211-217. https://doi.org/10.4274/tjh.galenos.2021.2020.0555