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

Sinan Mersin, Ayfer Gedük, Özgür Mehtap, Pınar Tarkun, Serkan Ünal, Merve Gökçen Polat, Kemal Aygün, Emel Merve Yenihayat, Hayrunnisa Albayrak, Abdullah Hacıhanifioğlu, Sinan Mersin, Ayfer Gedük, Özgür Mehtap, Pınar Tarkun, Serkan Ünal, Merve Gökçen Polat, Kemal Aygün, Emel Merve Yenihayat, Hayrunnisa Albayrak, Abdullah Hacıhanifioğlu

Abstract

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 subject.

Keywords: Bortezomib; Multiple myeloma; Equivalent.

Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
Evaluation of progression-free survival (PFS).

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.
    1. 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.
    1. 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.
    1. Field-Smith A, Morgan GJ, Davies FE. Bortezomib (Velcadetrade mark) in the treatment of multiple myeloma. Ther Clin Risk Manag. 2006;2:271–279.
    1. 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.
    1. Richardson PG, Mitsiades C, Hideshima T, Anderson KC. Proteasome inhibition in the treatment of cancer. Cell Cycle. 2005;4:290–296.
    1. 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.
    1. Borcade Drug Information. Available online at. [Internet]
    1. 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.
    1. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Washington, HHS, 2017. Available online at. [Internet] .
    1. 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.
    1. 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.
    1. Kanavos P. Do generics offer significant savings to the UK National Health Service? Curr Med Res Opin. 2007;23:105–116.
    1. 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.
    1. Borgheini G. The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs. Clin Ther. 2003;25:1578–1592.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren