Dr Ghia on Safety Considerations After Fixed-Duration Ibrutinib Plus Venetoclax in CLL

“In this final analysis, we showed that patients can be retreated, and there is a sustained response. Seventy-six percent of patients will achieve a response with either ibrutinib or ibrutinib plus venetoclax. Those who do not officially respond still have stable disease, and we have controlled the disease for at least 1.5 years.”

Paolo Ghia, MD, PhD, a full professor in medical oncology at Università Vita-Salute San Raffaele, director of the Strategic Research Program on CLL, and head of the Laboratory of B-Cell Neoplasia at the IRCCS Ospedale San Raffaele, discussed safety considerations following treatment with frontline fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) in patients with chronic lymphocytic leukemia (CLL).

Patients treated on the phase 2 CAPTIVATE trial (NCT02910583) were either treated with ibrutinib plus venetoclax or ibrutinib alone for 15 months, with all patients finishing treatment by the end of the 15 months, regardless of minimal residual disease (MRD) status. At the time of the final analysis, all patients had finished treatment, Ghia began. He noted that there were no immediate concerns regarding safety. However, in the analysis, there were 2 aspects of consideration, he stated. One was the effect of retreating patients and the potential for cumulative adverse effects occurring; nevertheless, there were no new safety signals, he explained. When retreating patients with CLL, he continues to select either ibrutinib alone or ibrutinib plus venetoclax, he asserted. Additionally, among patients included in the final analysis who developed secondary malignancies, the most common type was nonmelanoma skin cancers, Ghia asserted.

Furthermore, an aspect of consideration during the final analysis of the CAPTIVATE study was the number of sustained responses following retreatment with ibrutinib alone or ibrutinib plus venetoclax, Ghia continued. Notably, 76% and 82% of patients will achieve a response following treatment with either ibrutinib (n = 25) or ibrutinib plus venetoclax (n = 11), respectively, he emphasized. In patients who have stable disease but do not achieve a response to treatment, disease control has been shown for at least 1.5 years, according to Ghia. Ultimately, the progression-free survival data were promising, although follow-up time is currently short at 28.4 months for patients treated with ibrutinib monotherapy and 15.2 months for those treated with ibrutinib plus venetoclax.