The combination of the novel investigational agent ibrutinib with an established therapeutic antibody, rituximab, may present a safer and more effective option than the current standard chemotherapy-based treatment regimen for patients with high-risk Chronic Lymphocytic Leukaemia (CLL).

While current chemotherapy-based treatment options for CLL patients are effective, they come with toxic side effects that are challenging for elderly patients.

Physicians have long awaited new options that offer better tolerability. Ibrutinib is designed to selectively target leukaemia cell growth, with the aim of effectively treating the disease without the toxicities of chemotherapy.

Data from earlier studies of ibrutinib have shown it to be equally effective in both low- and high-risk CLL.

High-risk CLL patients typically have unfavorable responses to standard CLL therapies and a dismal outcome.

Such patients are characterized by presence of chromosomal abnormalities (i.e., deletions of chromosome 17p or 11q) or short remissions (less than 3 years) after standard chemo-immunotherapy. To develop an alternative therapy regimen for this patient population, researchers explored the combination of ibrutinib and the anti-CD20 antibody rituximab in high-risk CLL.

In this Phase II study conducted at The University of Texas MD Anderson Cancer Center in Houston, ibrutinib was given in combination with rituximab to evaluate its potential to accelerate and improve CLL patient responses.

Forty patients were treated with 420 mg of ibrutinib daily in combination with weekly rituximab for four weeks, followed by ibrutinib daily plus monthly rituximab until month six, followed by single-agent ibrutinib.

Positive responses to therapy were shown among the vast majority of treated patients. At four months of follow-up, the overall response rate was 85 percent and almost all (38 of 40) patients continued on therapy without disease progression.

Of the 20 patients evaluable for early response, 17 achieved a partial remission. Patient health questionnaires also noted improvements in health and the quality of life of all treated patients.

Overall, the regimen was well-tolerated among participants, with little severe toxicity that was largely unrelated and short in duration.

After treatment with ibrutinib-rituximab (iR) combination therapy, most cases of early lymphocytosis (increase in white blood cells that is a sign of infection), due to the ibrutinib-induced shift of CLL cells from lymph node tissues into the blood, peaked early and resolved; at four months of follow-up, only three treated patients had lymphocytosis that had not yet resolved.

This shorter lymphocytosis duration, when compared to single-agent use of ibrutinib, is presumably related to the addition of rituximab.

“We know that high-risk CLL patients struggle with the effects of standard chemo-immunotherapy and eventually become resistant. For these harder-to-treat patients, ibrutinib in combination with rituximab appears to be a safer option with high efficacy and without the related risks,” said Jan Burger, MD, PhD, lead author and Associate Professor of Medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston.

“Based on these promising results, we need larger-scale studies of ibrutinib-rituximab in high-risk CLL, with the goal of accelerating the development of this therapy for patients who most urgently need better options.”

Source: ASH