After more than 3 years of treatment, response to ibrutinib plus venetoclax was sustained despite planned discontinuation of therapy in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who achieved minimal residual disease (MRD) negativity, according to results of the Blood Cancer UK TAP CLARITY trial.

“Patients who do not show rapid disease clearance and have persistent MRD after 12 months of combination ibrutinib plus venetoclax usually have stable or slowly decreasing levels akin to that seen in ibrutinib monotherapy,” said Talha Munir, MBBS, of St James University Hospital, United Kingdom, who presented the study at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

The phase 2 trial included 50 patients with relapsed or refractory CLL. Patients had two months of ibrutinib followed by the addition of venetoclax at escalating doses. Paired peripheral blood and bone marrow samples were assessed at months 8, 14, and 26.


Continue Reading

If patients had confirmed complete response and MRD reduction less than 10-4 CLL cells (MRD4) in peripheral blood and bone marrow at month 8, ibrutinib and venetoclax could be stopped at month 14. If MRD4 was achieved at month 14 or month 26, treatment could be stopped at month 26. A study amendment allowed patients who did not achieved MRD4 at month 26 to have 12 months of additional venetoclax plus ibrutinib.

The MRD-negative rate in bone marrow at 12 months was 40%. The overall response rate was high with the combination, and complete remission (CR) and CR with incomplete marrow recovery rates increased with continuing therapy. The overall response rate at month 38 was 90%. Among the 23 patients who continued on therapy, the overall response rate was 85%.

At month 38, MRD4-negative rates were 50% and 40% in peripheral blood and bone marrow, respectively, in all evaluable patients.

Responses improved with continued treatment. Whereas 40% of patients achieved MRD4 at month 14, 48% achieved MRD4 in the bone marrow at month 26. MRD4 at month 38 was approximately 44%, but Dr Munir noted that 12 patients were not evaluable at month 38 primarily because of the COVID-19 pandemic.

The researchers found that the initial rate of disease depletion during the first 2 months of ibrutinib plus venetoclax exposure was highly predictive of longer-term response to combination ibrutinib plus venetoclax treatment.

Of the 25 patients who achieved undetectable MRD, 17 have sustained undetectable MRD, 5 are low MRD, one has high-MRD positivity, and 2 patients had insufficient follow-up. The median time off therapy is 1.5 years.

The median progression-free and overall survival is not yet reached. The estimated progression-free survival at 36 months was 95.9% and the estimated overall survival is 97.7%.

There were no new safety signals on prolonged follow-up, Dr Munir said. Two patients with COVID-19 infection have made good recoveries.

Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.

Reference

Munir T, Boucher RH, Webster N, et al. Continued long term responses to ibrutinib + venetoclax for relapsed/refractory CLL in the Blood Cancer UK TAP Clarity trial. Presented at:  the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 124.

This article originally appeared on Cancer Therapy Advisor