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ASH 2022: Dr. Tahla Munir on Predicting Responses to Combination Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

The Bottom Line:

For patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the response to combination ibrutinib plus venetoclax treatment in the first two months seems to predict who will have deep, sustained responses.

Who Performed the Research and Where Was it Presented:

Dr. Talha Munir from St. James’s University Hospital and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.

Background:

Combination treatment with ibrutinib plus venetoclax is very effective, and in August 2022, it received approval from the European Commission for use in previously untreated CLL / SLL. However, we are still waiting on FDA approval. This combination has been studied for treating relapsed/refractory CLL / SLL (CLARITY study) and first-line treatment (GLOW study, CAPTIVATE study, and this study).

In this interview, Dr. Brian Koffman interviewed Dr. Talha Munir, a hematologist at St. James’s University Hospital in Leeds, United Kingdom. They discussed the latest results from the CLARITY study, which examined whether early clearance of the disease predicts the durability of responses.

Methods and Participants:

The CLARITY study is a phase 2 clinical trial testing the combination of ibrutinib plus venetoclax in 50 patients with relapsed/refractory CLL. The length of treatment was guided by each patient’s response to therapy (i.e., if and when they achieved undetectable measurable residual disease [uMRD]).

Results:

  • The CLARITY study is now at five years of follow-up.
  • The progression-free survival is 78%, meaning 3 in 4 patients are still disease-free.
  • 9 in 10 patients are still alive.
  • There were no new safety signals.
  • There were some deaths from various causes including Richter transformation, Alzheimer’s, and disease progression, but none due to drug toxicity.
  • About half of the patients (n=25) were very sensitive to a combination of ibrutinib plus venetoclax. They had a very deep response in the first two months of treatment (2 log reduction MRD levels).
  • These responses were durable, with only two clinical progressions after 40 months.
  • 14 patients achieved uMRD within the first six months of treatment.
  • One of these patients relapsed at month 38, but all others remain progression-free.
  • The response to treatment in the first two months seems to predict who will have deep, sustained responses. Those who do not respond quickly may need a longer course of therapy or may want to consider other treatment options.

Conclusions:

For patients with relapsed/refractory CLL / SLL, the response to combination ibrutinib plus venetoclax treatment in the first two months seems to predict who will have deep, sustained responses. In this study, ibrutinib plus venetoclax was effective for treating relapsed/refractory CLL / SLL; further phase 3 studies that would potentially lead to approval have not been conducted yet as research interest shifted to using it as a first-line treatment.

Links and Resources:

Watch the interview on the abstract here:

You can read the actual ASH abstract here: MRD4 Eradication at 6 Months and Early Clearance of MRD with Combination of Ibrutinib Plus Venetoclax Results in Sustained Clinical and MRD Responses: Exploratory Analysis of the Blood Cancer UK TAP Clarity Study

Take care of yourself first.

Ann Liu, PhD