Frontline Imbruvica Plus Venclexta May Restore Immune Profiles in CLL

Firstline treatment with Imbruvica (ibrutinib) plus Venclexta (venetoclax) may restore normal blood immune composition in patients with chronic lymphocytic leukemia (CLL), as demonstrated in recent study findings.

The blood immune composition refers to the body’s ability to protect itself from infections and illnesses with red blood cells, white blood cells and platelets.

“Our findings suggest that (Imbruvica) plus (Venclexta) treatment restores a healthier immune profile in patients with CLL, with a totality of data demonstrating eradication of CLL cells, recovery of normal B cells and normalization of critical immune cells, including T-cell subsets, classical monocytes and (dendritic cell) counts,” the study authors wrote.

As it has not been previously studied, researchers aimed to assess the impact of firstline Imbruvica plus Venclexta on immune cells in patients with CLL. In this study, researchers analyzed data from 79 patients (median age, 59 years; 61% men) with CLL who were treated with three cycles of Imbruvica followed by 13 cycles of Imbruvica plus Venclexta.

Data from these patients were obtained as part of the minimal residual disease (MRD) cohort from the CAPITVATE trial. In particular, patients with confirmed undetectable MRD (or the absence of a very small number of cancer cells in the body after treatment) were randomly assigned to receive placebo (20 patients) or Imbruvica (20 patients). For patients who did not have confirmed MRD, they were assigned either Imbruvica alone (20 patients) or with Venclexta (19 patients).

Researchers compared immune cell subsets in samples that were collected at several time points throughout the study with those from healthy donors matched by age.

CLL cells decreased within approximately three cycles after initiating Venclexta. From cycle 16 on, these levels were similar to healthy donor levels in patients with confirmed undetectable MRD. CLL cell levels were slightly above healthy donor levels in patients without confirmed undetectable MRD.

By four months after cycle 16, normal B cells — which play an important role in identifying viruses and creating antibodies, for example — recovered to the levels seen in healthy donors in patients randomly assigned to placebo.

Within six months, abnormal counts of classical monocytes (immune cells created in bone marrow), dendritic cells (immune cells found in tissues like skin that boosts immune responses) and T cells (a type of white blood cell that protects the body from infection) had recovered to levels seen in healthy donors regardless of the treatment patients with CLL received.

“A reduction in CLL disease burden and the restoration of a healthier immune profile may reduce susceptibility to infections in patients with CLL,” the study authors wrote.

The number of infections that occurred in patients with CLL in this study generally decreased over time regardless of the treatment they were assigned to. Of note, the number of infections was lowest in patients randomly assigned to placebo within the 12-month period after cycle 16.

“These findings represent promising evidence for the restoration of important circulating adaptive and innate immune cells with (Imbruvica) plus (Venclexta), particularly in patients receiving a (fixed-duration) regimen (randomly assigned to placebo) with previously untreated CLL/SLL, and support the observed clinical efficacy of this regimen,” the study authors concluded.

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