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Progress in Relapsed/Refractory CLL Could Pave Way for Upfront Advances

Brandon Scalea
Published: Wednesday, Apr 03, 2019

Joseph D. Rosenblatt, MD

Joseph D. Rosenblatt, MD

Novel agents and combination regimens have changed the way clinicians view chronic lymphocytic leukemia (CLL) and bringing these new regimens to the upfront setting could translate to more patients achieving an improvement in progression-free survival (PFS) and possibly cures, said Joseph D. Rosenblatt, MD.

In addition, newer salvage agents are becoming available, such as duvelisib (Copiktra), which may eventually prove useful in the upfront setting, as well.

Rosenblatt, a professor of medicine and associate director of faculty development at Sylvester Comprehensive Cancer Center, University of Miami Health System, said that other agents, such as the BCL-2 inhibitor venetoclax (Venclexta) have proven to be highly effective options used alone or in various combinations for relapsed patients, as well as in the upfront setting.

In an interview during the 2019 OncLive® State of the Science Summit™ on Hematologic Malignancies, Rosenblatt discussed how advances made in CLL are changing the outlook for patients and predicted what can be accomplished in the near future.

OncLive: What are some advances that have been made in the treatment of CLL?

Rosenblatt: There have been some remarkable advances that have been made in just the last several months. Many of these were reported at the 2018 ASH Annual Meeting. There were other advances made in the past year that have changed the way we look at CLL and the way we approach this disease, both from the standpoint of initial therapy and the treatment of patients with relapsed/refractory disease.

A very important Alliance study was presented at the 2018 ASH Annual Meeting; during the plenary session. This study indicated that the use of the BTK inhibitor ibrutinib was superior to combination chemotherapy with bendamustine and rituximab (Rituxan; BR), a frequently used combination in patients older than 65 years, and was equivalent to use of ibrutinib (Imbruvica) and rituximab together. Neither of these results could have been predicted. This study had important messages with respect to the use of chemoimmunotherapy as opposed to some of the newer targeted agents used alone or in combination.

We are seeing very promising results with venetoclax, which is a drug that capitalizes on our understanding of the importance of BCL-2 in the biology of CLL. This agent actually mimics the effect of naturally occurring proteins that promote apoptosis and can reverse the effects of BCL-2 overexpression . When venetoclax is used in combination with rituximab, we have seen remarkably effective results in patients with relapsed/refractory disease. This combination could also be useful in the upfront setting, although this is just now being tested.

Could you expand on the data from the DUO study?

Quite a few of the patients in this study had poor-prognosis disease—including p53-mutant disease and 17p deletions that affect p53 function—and had received multiple prior treatments. This international study involved multiple centers internationally. On the basis of that study, duvelisib was approved by the FDA in September 2018 for the treatment of patients with relapsed/refractory disease who had received at 2 prior treatments.




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