Clinical Management of Relapsed CLL - Episode 4
Danielle Brander, MD:When considering second-line therapy for patients, I take into account multiple factors: the patient’s age and their functional status, their end organ function, what their goals of therapy are, and what their profile of prognostic markers looks like. Again, for patients who haven’t hadTP53dysfunction found in either deletion 17p orTP53mutation, testing for this is critically important as that will take you down a different route of considering options.
However, in general, in the second-line setting, patients who had chemotherapy as a first treatment are likely to have a much shorter duration of response if chemotherapy is used in the second-line setting. And this is increasingly why we’re using the novel targeted agents in the second-line setting over repeating chemotherapy, unless patients have a specific reason for the chemotherapy again or if they had a longer duration of response to chemoimmunotherapy as a first treatment.
For this patient who has a known deletion 17pbecause she’s overall functional, wants a goal of treatment to keep her in a good quality of life for as long as possible, and she has sufficient organ function—I consider treatments that I think are going to get her the best response and the best duration of response. For her, ibrutinib was not tolerated and she progressed very quickly. Because she had a high burden of disease in the bone marrow as well, I considered venetoclax, as this is approved for patients with relapsed refractory CLL with the deletion of 17p in order to achieve a deep response, such as a complete response that hopefully will last her for many years.
BCL-2 has long been recognized as an important antiapoptotic protein. That is, it pushes cells away from the normal process of programmed cell death. When you target BCL-2, you take away that antiapoptosis and restore the normal process of cell death. Therefore, when venetoclax targets this protein, which is especially important in keeping the CLL cells in the antiapoptotic side, you push them more to the state of cell death.
Venetoclax has been studied in several phase I, II clinical trials for patients with previously treated or relapsed refractory CLL. In one of those studies, venetoclax was additionally combined with rituximab, and for those 49 patients, over half the patients achieved a deep complete response to their therapy, which was especially impressive given many of them had had several lines of prior treatment.
Transcript edited for clarity.
Case: An Older Patient with Relapsed CLL