John Seymour, MBBS, FRACP, PhD, discusses the characteristics of patient subgroups with chronic lymphocytic leukemia who may benefit from curative treatment with fludarabine, cyclophosphamide, and rituximab.
John Seymour, MBBS, FRACP, PhD, director, Department of Hematology, the Peter MacCallum Cancer Centre, medical oncologist, Hematology Department, the Royal Melbourne Hospital, discusses the characteristics of patient subgroups with chronic lymphocytic leukemia (CLL) who may benefit from curative treatment with fludarabine, cyclophosphamide, and rituximab (Rituxan; FCR).
The curative potential of FCR therapy in CLL is best derived by specific subgroups defined by disease biology, age, and renal function. Identifying and appropriately selecting these patients for FCR treatment is a nuanced process, and remains a critical consideration when determining the optimal course of CLL management. Accordingly, investigators must understand patients' individual biologic profiles, as well as their disease-related risk, he explains.
These patients typically exhibit favorable disease biology, Seymour says, displaying either IGVH mutations or the absence of TP53alterations. The presence of other rare mutations may also factor into treatment decisions, he adds.
Additionally, consideration is given to a patient's age and renal function, as these factors influence a patient's ability to tolerate treatment with FCR, Seymour notes. Ideal candidates for FCR are typically younger than 65 years of age and possess adequate renal function, as indicated by a creatinine clearance above 60, he details. The subset of patients with curative potential is relatively small, accounting for approximately 15% of all patients with CLL who require treatment, Seymour elaborates. Of this 15%, approximately half achieve long-term remission with FCR and will not require any subsequent treatment throughout their natural lifespan.
Although targeted agents, such as BTK inhibitors or long-term venetoclax-based regimens, have demonstrated favorable short-term tolerability, they require continuous administration, Seymour continues. This is associated with an increased, cumulative risk of developing toxicities such cardiac arrhythmias, he states. Unfortunately, there is currently a lack of evidence demonstrating the curative potential of these time-limited venetoclax-based therapy, Seymour notes.