Safety/Efficacy of Ibrutinib Alone or With Venetoclax in CLL/SLL

Paolo Ghia, MD, PhD, deputy director of the Division of Experimental Oncology in San Raffaele Scientific Institute in Milan, Italy, full professor of medical oncology, a group leader in the B-cell Neoplasia Unit, and the head of the Strategic Research Program on CLL at the Università Vita Salute San Raffaele, discusses safety and efficacy findings from a 5-year update of the phase 2 CAPTIVATE trial (NCT02910583) in chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL).

In the phase 2 study, ibrutinib (Imbruvica) was given in combination with venetoclax (Venclexta) to patients with CLL/SLL. The combination showed clinically meaningful progression-free survival (PFS) and deep remission rates in this patient population.

Transcription:

0:09 | The interesting part is that virtually all patients responded to either ibrutinib monotherapy or ibrutinib and venetoclax. Some patients in the data that we presented have not yet been treated long enough to achieve a response. But now that we have followed them longer, we know that all patients at least achieved a partial response with the exception of 1 patient who had a Richter transformation, and that was diagnosed 1 month after starting the treatment. This is the first point, which is very relevant to know that patients who have received both classes of drugs in the frontline can still be retreated with these drugs. This is also possible because none of these patients developed a mutation in the BTK or PLCgamma2 molecules; that is a typical mechanism of resistance to ibrutinib, and also, nobody developed the classic traditional mutation on the BCL2 gene. That gives the rationale why all patients indeed responded to the treatment with the drugs.

1:34 | Being off therapy, the patient during the follow-up did not show any adverse events until they started the retreatment. We are following very closely the occurrence of other malignancies. Over 5 years, only 8% of the patients developed a second malignancy, and particularly skin cancer, which is known to be more common in patients with chronic lymphocytic leukemia.

2:04 | ...Now of course, we all want to know how long patients remain off therapy and they do not progress after a fixed duration of treatment, and at 54 months of follow-up, 70% of the patients are still responding, including patients with unmutated immunoglobulin genes, 68% of them are still responding. Patients with p53 aberration are losing a little bit earlier; the response is still 45% of them, still responding after 54 months of follow-up. So, this is very promising data and appears to be very effective mutually in all patients.