Choosing and sequencing novel drugs in CLL: dealing with an embarrassment of riches?

<span class="paragraphSection">It has been an extremely exciting time in CLL, for both clinical investigators and our patients. Between November 2013 and April 2016, three highly effective agents, each first in their class to be approved—ibrutinib (BTK inhibitor) [<a href="#mdx103-B1" class="reflinks">1</a>], idelalisib (PI3K inhibitor) [<a href="#mdx103-B2" class="reflinks">2</a>] and venetoclax (BH3-mimetic BCL2 antagonist) [<a href="#mdx103-B3" class="reflinks">3</a>]—received registrations for the treatment of CLL. Patients with relapsed CLL and adverse risk features such as deletion of chromosome 17p, complex karyotype or fludarabine-refractory disease, who previously were expected to live for 12 months or less [<a href="#mdx103-B4" class="reflinks">4</a>], are now achieving high-quality remissions that persist for 2 years or more [<a href="#mdx103-B1" class="reflinks">1–3</a>]. With the completion and reporting of the RESONATE-2 study showing superiority of ibrutinib over chlorambucil as frontline treatment of CLL in older patients<a href="#mdx103-B5" class="reflinks">⁵</a>, many patients now commence novel kinase inhibitors as their first CLL therapy.</span>

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