Bendamustin: stari lijek u novoj eri za bolesnike s ne-Hodgkinovim limfomima i kroničnom limfocitnom leukemijom

Abstract

The aim of this review is to present data on bendamustine, a non-cross resistant alkylating agent, alone or in combination for treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Bendamustine is currently approved for rituximab-resistant indolent NHL and CLL in patients not fit for conventional chemotherapy. Recent studies have shown superiority of bendamustine combination with rituximab (B-R) in first line treatment of indolent NHLs and mantle cell lymphoma, suggesting a shift of the standard of care in this setting. B-R regimen has also shown efficacy in relapsed setting suggesting the possible treatment option for patients failing conventional chemotherapy. In rituximab-resistant NHL, the recent GADOLIN study exploring the addition of obinutuzumab to bendamustine has yielded impressive result changing the standard of care in this hard-to-treat population. Concerning CLL, despite inferiority to the standard of care in young fit patients, as defined in CLL10 study, B-R has yielded a more beneficial toxicity profile and its use in first line treatment should be decided individually. In relapsed setting, the addition of ibrutinib to B-R has shown superior results compared to B-R alone, possibly changing the paradigm of treatment of relapsed CLL. In conclusion, bendamustine as a single agent or in combinations has shown activity with acceptable toxic profile in the treatment of patients with indolent NHLs or CLL without del(17p) mutation.Cilj ovoga preglednog rada je procijeniti aktivnost bendamustina te njegovih kombinacija u ne-Hodgkinovim limfomima (NHL) i kroničnoj limfocitnoj leukemiji (KLL). Bendamustin je sada indiciran u Republici Hrvatskoj za liječenje rituksimab-rezistentnog NHL-a i u bolesnika s KLL-om koji nisu kandidati za konvencionalnu terapiju. No, kombinacija bendamustina s rituksimabom (B-R) u prvoj liniji terapije indolentnog NHL-a i limfoma plaštene zone pokazala se boljom od konvencionalne kemoterapije pa bi B-R trebao postati zlatni standard u prvoj liniji liječenja ovih limfoma. Protokol B-R ­također ima aktivnost u relapsnom indolentnom NHL-u te predstavlja opciju za bolesnike koji su progredirali nakon konvencionalne kemoterapije. U rituksimab-rezistentnom NHL-u nedavna studija GADOLIN koja je proučavala dodatak ­obinutuzumaba bendamustinu pokazala je jasnu superiornost prema bendamustinu i promijenila zlatni standard u ovoj ­populaciji zahtjevnoj za liječenje. U KLL-u usprkos inferiornosti B-R prema FCR-u u studiji CLL10 B-R je bio obilježen boljim profilom toksičnosti te se može ponuditi pojedinim bolesnicima na temelju individualizirane odluke. U relapsnom okružju KLL-a dodatak ibrutiniba protokolu B-R pokazao je superiornost prema B-R s mogućom promjenom paradigme liječenja ovih bolesnika. Zaključno, bendamustin sam ili u kombinacijama pokazao je visoku aktivnost s povoljnim toksičnim profilom u liječenju indolentnih NHL-a i KLL bez mutacije del(17p)

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