The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

Treatment with the combination of first-line ibrutinib plus venetoclax conferred high rates of undetectable minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL), according to primary results from the MRD-guided randomization phase of the CAPTIVATE trial (ClinicalTrials.gov Identifier: NCT02910583).

“[This combination] is an all-oral, once-daily, fixed duration regimen that achieves undetectable MRD in blood or bone marrow in three-quarters of patients after 12 cycles of combined treatment,” said  William G. Wierda, MD, PhD, of University of Texas MD Anderson Cancer Center, who presented the results at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.


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CAPTIVATE is a phase 2 study of first-line ibrutinib plus venetoclax. Patients 70 years or younger received 3 cycles of ibrutinib lead-in followed by 12 cycles of combined ibrutinib plus venetoclax.

The median age of patients was 58 years. Sixty percent of patients had unmutated IGHV, almost 20% had complex karyotype, 20% had del(17p)/TP53 mutations, and 17% had del(11q).

After ibrutinib lead-in, 90% of patients with baseline-high tumor lysis syndrome (TLS) risk shifted to medium- or low-TLS risk categories. About three-quarters of evaluable patients had undetectable MRD in peripheral blood (75%) or bone marrow (72%). In patients with undetectable MRD in peripheral blood with matched bone marrow samples at cycle 16, 95% had undetectable MRD in both.

Patients who achieved undetectable MRD were assigned to the MRD cohort and randomly assigned to receive placebo or further treatment with the combination. The primary endpoint was disease-free survival at 1 year.

In the undetectable-MRD group, the 1-year disease-free survival rate was not significantly different for patients assigned to placebo or further treatment (95.3% vs. 100%).

The median follow-up was 31.3 months. The 30-month progression-free survival rates were more than 95% across all randomized arms.

For patients who did not achieve undetectable MRD at the end of 12 cycles of combined treatment, there was improvement in MRD status with continued combined therapy vs single-agent ibrutinib. This supports a fixed-duration treatment of 12 cycles and treatment discontinuation for patients that achieve confirmed undetectable MRD, Dr Wierda said.

“There were no safety concerns with this highly active combination of first-line ibrutinib and venetoclax,” Dr Wierda said. Few patients in the study required dose adjustment or discontinuation.

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

Wierda WG, Tam CS, Allan JN, et al. Ibrutinib (Ibr) plus venetoclax (Ven) for first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL):1-year disease-free survival (DFS) results from the MRD cohort of the phase 2 CAPTIVATE study. Presented at 62nd: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. December. 5-8, 2020. Abstract 123.

This article originally appeared on Cancer Therapy Advisor