Long Term Follow-Up With Ibrutinib + Venetoclax to Treat Chronic Lymphocytic Leukemia

Ryan Jacobs, MD, from the Atrium Health Levine Cancer Institute in Charlotte, North Carolina, discusses 4-year follow up data from the phase 2 CAPTIVATE study, which evaluated ibrutinib plus venetoclax as a first-line treatment for chronic lymphocytic leukemia (CLL). These findings were recently presented at this year’s American Society of Hematology Meeting & Exposition (ASH 2022).

CLL is a rare blood cancer resulting in a build-up of lymphocytes in bone marrow, lymph nodes, and blood. The disease is treatable, but relapse is very common. The CAPTIVATE study is a multicenter, double-blind, phase 2 study with previously untreated CLL patients under the age of 70 years. Patients were given 3 cycles of ibrutinib and an additional 13 cycles of ibrutinib plus venetoclax. Patients who had confirmed rates of undetectable minimal residual disease (uMRD) were then randomized to receive ibrutinib or placebo. Patients who did not meet the definition of undetectable MRD were randomized to receive ibrutinib alone or continued combination therapy. At two years after randomization, disease-free survival (DFS) rates were similar in patients from these two arms (95% and 100%, respectively).

At ASH 2022, efficacy and safety results were presented with median 56-month follow-up (median 41 months post-randomization).

As Dr. Jacobs explains, in the placebo arm of patients with confirmed uMRD, 63% of patients have now achieved a best response of complete response (an increase from 60% at 2-year follow-up). In patients who continued ibrutinib, 81% achieved complete response (an increase from 72% at 2-year follow-up). Rates of uMRD remained stable from year 2 to year 3 post randomization (placebo: 56% [n=24] and 58% [n=25]; ibrutinib: 60% [n=26] and 63% [n=27], respectively). The 3-year DFS rate was 85% with placebo and 93% among patients who continued ibrutinib (p=0.1621). The 4-year PFS was 88% with placebo and 95% with continued ibrutinib. 4-year overall survival was 100% (0 deaths) and 98% in placebo and ibrutinib arms, respectively.

Prevalence of adverse events during the post-randomization period was generally stable in each arm. New occurrences of hypertension in post randomization years 1-3 were generally lower with placebo compared to ibrutinib (year 1: n=1/43 vs n=3/43; year 2, n=1/41 vs n=4/41; year 3, n=3/38 vs n=2/41, respectively). No new atrial fibrillation or grade ≥3 hemorrhage events occurred in the placebo arm during the 3-year post randomization period; One patient in the ibrutinib arm had atrial fibrillation in year 2 post-randomization. In the year 3 post-randomization, no patients had dose reduction or discontinuation due to an AE in the placebo arm while 1/41 patients had a dose reduction and 2/41 discontinued ibrutinib due to an AE. In total, seven and two patients experienced progressive disease in the placebo and ibrutinib arms, respectively; four of those seven patients in the placebo arm have initiated subsequent therapy (three with ibrutinib, one with other agent/s). No patients in the ibrutinib arm have initiated subsequent therapies.

For more information about CLL and other rare cancers, visit checkrare.com/diseases/cancer

• Category

  Leukemia - Chronic Lymphocytic - CLL