Oleh Admin Kalbe Medical pada February 15, 2018 07:30

Denosumab telah Disetujui oleh US FDA untuk Pasien dengan Multipel Mieloma

US FDA menyetujui perluasan indikasi denosumab untuk memasukkan penyakit multipel mieloma. Sebelumnya denosumab diindikasikan untuk pencegahan kejadian terkait tulang dan sendi pada pasien dengan metastasis tulang karena tumor solid, tumor giant cell tulang yang tidak dapat dibedah, dan hiperkalsemia pada keganasan refrakter terhadap terapi bisphosphonate. Pada penyakit multipel mieloma, osteolitik (tulang lisis) sering dijumpai pada 80% pasien dan gangguan ginjal dapat dijumpai pada sekitar 60% pasien.

Denosumab merupakan antibodi monoklonal imunoglobulin G2 fully human dengan afinitas dan spesifisitas tinggi untuk RANKL (receptor activator of nuclear faktor kB ligand). RANKL berperan dalam peningkatan risiko kejadian terkait tulang dan sendi pada multipel mieloma. Persetujuan indikasi multipel mieloma adalah berdasarkan hasil penelitian fase III, tersamar ganda, yang melibatkan 1.718 pasien multipel mieloma newly diagnosed. Pasien mendapat denosumab 120 mg secara subkutan atau zoledronic acid 4 mg IV setiap 4 minggu. Pasien diberikan terapi anti-mieloma. Pasien dengan bersihan kreatinin awal <30 mL/menit masuk dalam kriteria eksklusi karena pembatasan penggunaan zoledronic acid.

Dalam penelitian tersebut, denosumab non-inferior dibandingkan zoledronic acid dalam menunda waktu sampai terjadinya kejadian tulang dan sendi (22,83 bulan vs 23,98 bulan). Selain itu, disebutkan pula bahwa overall survival (OS) sebanding pada kedua kelompok pasien, sedangkan median progression free survival (PFS) pada pasien denosumab adalah 46,1 bulan dibandingkan 35,4 bulan pada pasien zoledronic acid.

Denosumab disebutkan tidak diekskresikan melalui ginjal, yang mana hal ini merupakan modalitas baru untuk pasien dengan gangguan ginjal yang berisiko mengalami komplikasi pada tulang. Dibandingkan zoledronic acid, efek samping pada ginjal lebih jarang dijumpai pada pasien yang mendapat denosumab. Kejadian ini lebih terlihat pada pasien dengan bersihan kreatinin ≤60 mL/menit. Sejumlah 12,5% pasien pada kelompok denosumab dan 20,8% pasien pada kelompok zoledronic acid mengalami peningkatan kreatinin. Efek samping serius yang dapat dijumpai adalah hipokalsemia (denosumab vs zoledronic acid: 16,9% vs 12,4%) dan osteonekrosis rahang (denosumab vs zoledronic acid: 4,1% vs 2,8%)

Dengan hasil bahwa denosumab non-inferior dibandingkan zoledronic acid dalam hal efikasi terhadap kejadian terkait skeletal dan memiliki kelebihan dalam hal profil toksisitas (efek samping pada ginjal lebih sedikit), denosumab merupakan alternatif dari zoledronic acid untuk pasien multipel mieloma newly diagnosed. (HLI)

Image : Ilustrasi
Referensi:
1.Nam J. FDA approves expanding denosumab indication to include multiple myeloma. Cancer Therapy Advisor [Internet]. 2018 Jan 5 [cited 2018 Jan 17]. Available from: http://www.cancertherapyadvisor.com/hematologic-cancers/denosumab-multiple-myeloma-fda-approval-indication-treatment/article/735262/
2.Yee AJ, Raje NS. Denosumab for the treatment of bone disease in solid tumors and multiple myeloma. Future Oncol. 2017. doi: 10.2217/fon-2017-0403.
3.Melville NA. Denosumab shows benefits in multipel myeloma bone disease. Medscape [Internet]. 2017 June 27 [cited 2018 Jan 17]. Available from: https://www.medscape.com/viewarticle/882160#vp_1

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## jhon J
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Dalam penelitian best restaurants near me open now tersebut, denosumab non-inferior dibandingkan zoledronic acid dalam menunda waktu sampai
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