Updated CAPTIVATE Data Continues to Show the Benefits of Fixed-Duration Ibrutinib-Venetoclax in First-Line CLL

Patients with chronic lymphocytic leukemia who were treated with first-line ibrutinib and venetoclax continued to demonstrate profound and lasting responses with new data showing additional benefit from continued ibrutinib therapy after 2 years.

Results from the Phase 2 CAPTIVATE trial (NCT02910583) that were presented at the 2021 American Society of Hematology annual meeting showed that the use of ibrutinib (Imbruvica) plus venetoclax (Venclexta) in first-line treatment for patients with previously untreated chronic lymphocytic leukemia (CLL) continued to result in profound and lasting responses. Continuous treatment in some patients based on minimal evidence of residual disease has shown benefit in addition to fixed-course therapy.

“These results in patients with [undetectable MRD] receiving treatment with a fixed duration supports the potential for remission without treatment with first-line ibrutinib plus venetoclax, an all-oral, once-daily, chemotherapy-free regimen that provides deep and lasting responses in patients with CLL ” , wrote the study authors. in the presentation.

The Phase 2 CAPTIVATE trial consisted of 164 patients

After the 12 cycles, patients with confirmed undetectable MRD (uMRD) were randomized to receive placebo (n = 43) or ibrutinib (n = 43) and those without uMRD to receive either ibrutinib (n = 31 ) or ibrutinib plus venetoclax (n = 32).

In particular, most of the patients included in the study had high-risk factors such as unmutated IGHV (60%), del (17p) /TP53 mutation (20%), complex karyotype (19%) and del (11q) without del (17p) (17%).

No new disease-free survival (DFS) events have occurred since the primary analysis in patients with confirmed uMRD randomized to receive placebo versus ibrutinib. In patients with confirmed uMRD after randomization, the 2-year disease-free survival (DFS) rates remained unchanged at 95% in the placebo arm and 100% with ibrutinib, for a difference of 4.7% (95% CI, -1.6-10.9; overall log-rank, P =. 1573). In addition, modest improvements in complete response (CR) rates were seen in the placebo and ibrutinib arms, including CR with incomplete bone marrow recovery (CRi).

At a median follow-up of 38 months, the 36-month PFS in the confirmed uMRD population was 95.3% (95% CI, 82.7-98.8) in patients who received placebo and 100% in those assigned to ibrutinib (95% CI, 100-100).

In patients without confirmed uMRD, improvements in uMRD levels, CR / RCi rates were higher with ibrutinib plus venetoclax than with ibrutinib alone after randomization. In addition, the 36-month PFS rates among these patients after randomization were 96.7% in both ibrutinib (n = 31) and ibrutinib plus venetoclax (n = 32) arms.

The study authors noted that as of August 4, 2021, 12 patients whose disease had progressed after fixed-course treatment with the combination were retreated with ibrutinib alone. At a median follow-up of 4.9 months, 9 patients had RP and 3 have pending responses.

“Early data suggests that patients who progress after fixed-course treatment with ibrutinib plus venetoclax may successfully withdraw with ibrutinib as monotherapy,” the researchers wrote.

The most common grade 3/4 adverse events were neutropenia (36%), hypertension (10%), thrombocytopenia (5%) and diarrhea (5%). With up to 48 months of treatment, 13% of patients discontinued ibrutinib or venetoclax due to adverse events without any new safety signal appearing during additional follow-up.

“With an additional year of follow-up since the primary analysis, there were no new relapses of MRD, PD or death in patients with confirmed uMRD treated with placebo or ibrutinib,” wrote in the presentation.

The authors concluded by noting that there are still several ongoing global phase 2 and phase 3 studies evaluating time-limited treatment with the combination of ibrutinib and venetoclax.


Ghia, P, Allan, J, Siddiqi, T et al. First-line treatment with Ibrutinib (Ibr) Plus Venetoclax (Ven) for chronic lymphocytic leukemia (CLL): 2-year post-randomization disease-free survival (SFM) results of the minimal residual disease cohort (MRD) phase 2 Captivate Study. Presented at the 2021 ASH Annual Meeting and Exhibition; December 11-14, 2021; Virtual. Summary 68.

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