The Bruton’s tyrosine kinase inhibitor ibrutinib (PCI-32765) promotes high response Rate, durable remissions, and is tolerable in treatment naïve and relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma patients including those with high-risk disease: Updated results of 116 patients in Phase Ib/II study

New research demonstrates that a novel investigational therapeutic agent called ibrutinib may be an effective and safe targeted treatment option for previously untreated, hard-to-treat, and relapsed patients with chronic lymphocytic leukaemia (CLL).

Primary treatment for CLL includes a combined chemotherapy-based regimen with fludarabine and cyclophosphamide, along with the immune therapy rituximab.

While rituximab is effective, it is generally not well tolerated among elderly patients. Treatment with this drug also compromises the immune system by attacking both cancerous and normal cells, putting patients at risk for a range of infections and increasing their risk of developing treatment-related acute myeloid leukaemia.

To understand if ibrutinib may be effective for elderly CLL patients and to identify which patients might benefit most from the drug, researchers enrolled 116 CLL patient participants in several treatment cohorts: patients who were never treated (the treatment-naïve group), those who had received two or more prior therapies (the relapsed/refractory group), those who had relapsed within two years of treatment (the high-risk group), and those over age 65.

Two oral dosing regimens (420 mg or 840 mg daily) of ibrutinib were used. The primary goal of the study was to determine the safety of the low and high doses; secondary objectives included efficacy, measures of the intensity of the drug’s effect in the body, and the long-term safety of administering this therapy continuously until relapse.

The study found that response to therapy was high across the cohorts, with largely manageable toxicities.

Previously untreated elderly patients responded best to the agent, with 71 percent experiencing a complete or partial response at either treatment dose.

The same response was observed in 67 percent of the relapsed patients and 50 percent of the high-risk patient cohort. After 22 months of follow-up, the disease had not progressed in 96 percent of previously untreated patients and 76 percent of relapsed and high-risk patients.

The treatment regimen was generally well-tolerated, as only non-severe side effects were observed, including diarrhea, fatigue, chest infection, rash, nausea, joint pain, and infrequent and transient low blood counts. Investigators found no evidence of cumulative toxicity or long-term safety concerns with a median follow-up of 16 months for treated patients.

These results demonstrate ibrutinib’s potential as a highly active, well-tolerated first-line therapy for CLL.

“As we learn more about how to target specific essential survival signals and communications pathways in cancer, we are improving our ability to effectively treat the disease while avoiding the toxicities of chemotherapy and potential relapse,” said John C. Byrd, MD, lead author and Director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute in Columbus. “If we can replicate these high survival rates and good tolerability with ibrutinib through larger scale Phase III studies, we may find it to be an extremely valuable new therapy for not just elderly, but for all CLL patients.”

Source: ASH