Imbruvica, Venclexta Combo Offers Chemotherapy-Free Regimen for Patients with CLL


Recent results demonstrated durable responses and no new side effects for Venclexta plus Imbruvica in pretreated chronic lymphocytic leukemia.

Imbruvica (ibrutinib) plus Venclexta (venetoclax) demonstrated durable responses that support the combination as first-line therapy for patients with chronic lymphocytic leukemia (CLL), according to recent study results.

“These results in patients with confirmed (undetectable minimal residual disease) receiving fix duration treatment (randomized to placebo), support the potential for treatment-free remission with first-line, fixed duration (Imbruvica) plus (Venclexta), an all-oral, once daily, chemotherapy-free regimen that provides deep durable responses in patients with CLL,” the researchers wrote.

The trial enrolled 164 patients younger than 70 years of age (median age 58 years) with previously untreated CLL to receive three cycles of Imbruvica followed by 12 cycles of combined Imbruvica plus Venclexta.

After the 12 cycles patients were divided by undetectable minimal residual disease (uMRD) status, which is when patients have only a small amount of cancer cells after treatment. Then, they were randomized to receive ether placebo or Venclexta or Venclexta plus Imbruvica. Ultimately there were four patient groups:

  • Those with confirmed uMRD given placebo (43 patients)
  • Those with confirmed uMRD given Imbruvica (43 patients)
  • Those without uMRD given Imbruvica (31 patients)
  • Those without uMRD given Imbruvica plus Venclexta (32 patients).

Notably, most 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%).

Results, which were presented at the 2021 ASH Annual Meeting, demonstrated that in patients with confirmed uMRD, the two-year disease free survival (defined as the time from treatment to recurrence, metastasis or death) rates stayed at 95% in the placebo group compared to 100% for those treated with Imbruvica. Additionally, modest improvements in complete response (or the disappearance of cancer as a response to treatment; CR) rates were observed in both the placebo and Imbruvica arms, including CR with incomplete bone marrow recovery (CRi).

With a median follow up of 38 months, 36-month overall survival (OS) was 99% overall, with progression free survival (time during and after treatment when the patient lives without disease progression; PFS) rates of 95.3% in placebo, and 100% in Imbruvica alone.

In patients without confirmed uMRD, improvements in uMRD rates, CR/CRi rates were greater with Imbruvica plus Venclexta compared with Imbruvica alone. Thirty-six—month PFS rates were 96.7% for both arms.

As of Aug. 4,2021, 12 patients who progressed after fixed duration treatment with the combination have been retreated with Imbruvica alone.

“Early data suggest that patients who progress after fixed duration treatment with (Imbruvica plus Venclexta) can be successfully retreated with single-agent (Imbruvica),” the researchers wrote.

The most common severe side effects included low white blood cell count (36%), hypertension (10%), low blood platelet count (5%) and diarrhea (5%). In up to 48 months of treatment, 13% of patients discontinued due to side effects and no new safety signals were observed.

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