Ibrutinib Retreatment Yields High Responses in Chronic Lymphocytic Leukemia


Fixed-dose ibrutinib plus venetoclax produces limited second malignancies among patients with chronic lymphocytic leukemia, says Paolo Ghia, MD, PhD.

Nearly all patients with chronic lymphocytic leukemia (CLL) included in the phase 2 CAPTIVATE trial (NCT02910583) achieved a response after reinitiating ibrutinib (Imbruvica) treatment with or without venetoclax (Venclexta), according to Paolo Ghia, MD, PhD in a conversation with CancerNetwork® at the 2023 American Society of Hematology (ASH) Annual Meeting.

The objective response rate (ORR) in patients treated retreated with ibrutinib monotherapy (n = 21) was 86%, 83% in those who were retreated with ibrutinib plus venetoclax (n = 6). Partial responses were observed in 81% and 50% of patients in each respective group.

Ghia, a full professor in Medical Oncology at Università Vita-Salute San Raffaele, and the deputy chairman of the Division of Experimental Oncology at IRCCS Ospedale San Raffaele, Milano, also said that study treatment led to the development of a secondary malignancy in 8% of patients.


The interesting point is that virtually all patients responded to either ibrutinib monotherapy or ibrutinib plus venetoclax. Some patients, [based on] the data that we presented from the outset, had not yet been treated long enough to achieve a response. But now that we have followed up with them up longer, we know that all patients at least achieve a partial response with the exception of 1 patient who had a Richter transformation diagnosed 1 month after starting the treatment.

Patients who have received both classes of drugs in the frontline can still be re-treated with these drugs. This is also possible because as we presented in the abstract, none of these patients developed a mutation in the BTK or PLCG2 molecules; that is a typical mechanism of resistance to ibrutinib. Also, nobody developed the classic traditional mutations on the BCL2 gene. That gives the rationale why all patients indeed responded to the treatment with the drugs. Of course, with being off therapy, [we monitored] the patients who did not show any adverse [effect] during the follow up until they started the treatment. We are following very closely the occurrence of other malignancies. Over 5 years, only 8% of the patients developed a second malignancy, particularly skin cancer, which is known to be more common in patients with [CLL].


Ghia P, Wierda WG, Barr PM, et al. Relapse after first-line fixed duration ibrutinib + venetoclax: high response rates to ibrutinib retreatment and absence of BTK Mutations in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with up to 5 years of follow-up in the phase 2 Captivate study. Blood. 2023;142(suppl 1):633. doi:10.1182/blood-2023-187128

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