SAN FRANCISCO – Pursue a deep remission that allows a patient to stay treatment free for some period of time, or go for long-term disease control that might not allow for a drug holiday?
It’s a key decision facing physicians in the frontline setting of chronic lymphocytic leukemia, William Wierda, MD, PhD, said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.
Dr. William G. Wierda
For those with del(17p) or TP53 mutations, it’s probably best to aim for durable disease control with ibrutinib or high-dose methylprednisolone, plus an anti-CD20 monoclonal antibody, explained Dr. Wierda, medical director of the department of leukemia at MD Anderson Cancer Center, Houston.
The decision is more uncertain for those who are older or frail, he added.
“This is really where we need to select the option based on what our preference is, what our patient’s preference is, and have an understanding of the durability and toxicities with remission with the oral agent versus the toxicities and responses with regard to the chemoimmunotherapy regimens,” Dr. Wierda explained.
For those who are younger and fit, a chemoimmunotherapy regimen likely makes the most sense for those with a mutated IgHV gene, he said, because those patients have been shown to have a better prognosis on the fludarabine-cyclophosphamide-rituximab (FCR) combination.
Those with an unmutated IgHV gene probably should be approached differently, he added. “I know if they get FCR treatment, they will eventually relapse and progress. So, saving chemoimmunotherapy for later is an important endpoint.”
For relapsed patients who’ve had prior chemoimmunotherapy or who have del(17p) or TP53 mutations, options include ibrutinib, venetoclax with or without rituximab, idelalisib with or without rituximab, high-dose methylprednisolone plus an anti-CD20 monoclonal antibody, or lenalidomide plus an anti-CD20 monoclonal antibody.
For patients who’ve already had prior experience with a BTK inhibitor such as ibrutinib, Dr. Wierda suggested venetoclax, idelalisib with or without rituximab, chemoimmunotherapy if they’ve had no prior treatment, or high-dose methylprednisolone with an anti-CD20 monoclonal antibody.
It’s important to keep in mind ibrutinib’s effectiveness in that setting, Dr. Wierda noted. “You can effectively salvage patients with ibrutinib nearly as effectively as you can in the frontline setting.”
A recent study found that, for patients refractory to a kinase inhibitor, switching to a different kinase inhibitor was better than chemoimmunotherapy combinations. Researchers also found that using venetoclax after ibrutinib failure could be better than idelalisib (Ann Oncol. 2017 May 1;28[5]:1050-6)
Trials underway are testing first-line chemoimmunotherapy regimens to reach minimal residual disease-negativity, Dr. Wierda said, and examining combinations in the sequencing of small-molecule inhibitors for patients who have the unmutated IgHV gene.
“We’re also looking at consolidation strategies and have a definite interest in making progress for Richter’s transformation,” he added, an uncommon phenomenon that, in most cases, involves slow-growing CLL becoming aggressive diffuse large B-cell lymphoma. “We don’t know as much as we should know about it, and we have very few effective therapies for it.”
Dr. Wierda reported financial relationships with AbbVie, Celgene, Genentech, Merck, Novartis, Roche, and other companies.