Predictors of therapeutic and adverse effects outcomes of acalabrutinib used in the treatment of chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a cancer that begins in white blood cells known as B lymphocytes, which are part of the bodies immune system, causing them to multiply uncontrollably, crowding out healthy blood cells and weakening the immune system. CLL is the most common type of leukemia in adults, affecting over 200,000 people in the United States alone.

Over the past decade, treatment has shifted from chemotherapy to targeted therapies such as Bruton tyrosine kinase inhibitors (BTKi). Chemotherapy works by killing rapidly dividing cells such as cancer cells but it also affects healthy cells, while targeted therapy is a type of cancer treatment that utilizes drugs designed to ‘target’ cancer cells without affecting normal cells. BTKi's work by blocking Bruton tyrosine kinase (BTK), a protein critical for B lymphocyte cell survival. Ibrutinib, the first approved BTKi therapy, revolutionized CLL treatment by improving survival, but its long-term use is limited by resistance (when a cancer no longer responds to the therapy) and side effects. This led to the development of second generation BTKi’s such as acalabrutinib, which is more specific and better tolerated.

Despite the clinical success of acalabrutinib and the expansion of treatment options, significant challenges persist. For instance, cancer patients often take multiple medications for other conditions, such as prescription drugs, over-the-counter drugs, or dietary supplements, also known as concomitant medications , which can potentially alter acalabrutinib’s efficacy (how well it works) and impact patient outcomes. Additionally, there remains a lack of personalized prognostic (the likely outcome of the disease) and predictive measures to inform patient treatment benefit. This is particularly evident in the limited use of Patient-Reported Outcomes (PROs), which are self-reported measures capturing diverse elements of a patient's well-being, including emotional, physical, and disease-specific factors.

Our research has previously identified associations between concomitant medications and treatment outcomes in multiple myeloma patients receiving targeted therapy. Additionally, we have evaluated the prognostic and predictive value of PROs across various cancers, demonstrating that factors such as physical function predict survival and side effects. However, limited research has explored these associations in CLL patients initiating acalabrutinib-based regimens. Therefore, this study aims to use randomized clinical trial data to assess the association of concomitant medications and PROs in this population.

By integrating demographic information, such as age, sex and ethnicity, concomitant medication records, PROs, and laboratory data, such as blood tests, the study will employ advanced statistical techniques to uncover critical associations. By identifying the potential influence of concomitant medications and PROs on treatment outcomes, this research seeks to enhance medication management and establish PROs as predictive tools for clinical decision-making. This evidence-based, personalized approach has the potential to enable clinicians to optimize treatment strategies, tailor medication regimens, and manage drug interactions more effectively.