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Drug Duo Shows Promise in Treating Chronic Lymphocytic Leukemia


A new drug combination bested current standard of care in a clinical trial.

The treatment of chronic lymphocytic leukemia (CLL) is continuing to change, and shows no signs of slowing down, according to Alan Skarbnik, M.D., a staff physician at the Department of Bone Marrow Transplant, Department of Lymphoma in the John Theurer Cancer Center.

“For the past several years, CLL has been an ever-changing landscape with newer and more effective drugs, so it is interesting to see where the field is headed,” Skarbnik said in an interview with OncLive, a sister publication of CURE.

One particularly exciting advancement came from the phase 3 MURANO trial, presented at the 2017 American Society of Hematology (ASH) Annual meeting. Skarbnik called MURANO, “the biggest splash at the 2017 ASH Annual Meeting.”

MURANO proved that a combination of Venclexta (venetoclax) plus Rituxan (rituximab) reduced the risk of disease progression by 83 percent compared to the standard of care regimen, bensamustine plus Rituxan (BR), for patients with relapsed or refractory CLL who had at least one chemotherapy treatment in the past.

Two-year progression-free survival rates were 84.9 percent for patients on Venxlexta plus Rituxan versus 36.3 percent for BR, and overall response rates were 93.3 percent versus 67.7 percent for the combination compared to the standard of care, respectively.

“There was a very significant difference in response rates for this patient population,” Skarbnik said.

In the trial, while BR was given in its usual six cycles, patients randomized to the Venclexta/Rituxan combination were given Rituxan for six months after the ramp-up of Venclexta, which was set to be administered for two years.

The new combination showed promise regarding minimal residual disease (MRD), too. At the nine-month analysis, 60 percent of patients in the combination arm were MRD-negativite, compared to only 13 percent in the BR arm.

MRD refers to the small number of leftover disease cells that remain in a patient’s body after he or she undergoes treatment. If a patient has no detectable leukemia cells, they are deemed to be MRD-negativite.

“Everyone who achieved MRD negativity had a much longer progression-free survival. That adds to the importance of achieving that status, and it shows that ventoclax/rituximab is likely a much better choice for patients with relapsed disease because rates of MRD negativity are much higher,” Skarbnik said. “It is something that we need to look into further in trials, and it may be a goal for oncologists.”

Promising outcomes of the drug duo seemed to be lasting. After stopping the two-year therapy of Venclexta and Rituxan, 90 percent of patients did not need additional therapy. This can offer a beacon of hope to patients with CLL who were previously told that they might need to be on therapy for the rest of their lives.

“This may be an attractive approach for patients because many don’t want to be on a pill for the rest of their lives,” Skarbnik said.

But as these exciting advances continue to unfold and more patients are entering long-term remissions, Skarbnik said that there is still work that needs to be done.

“I want CLL to be cured. The idea that CLL is an incurable disease is changing,” he said. “We have to find either the right combination of agents or the right sequence of achieve to achieve this goal, but it is possible.”

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