Interview: Different perspectives on how to define success in CLL

©Peter MacCallum Cancer Centre  – John F. Seymour, MBBS, FRACP, PhD, Department of Haematology, Royal Melbourne Hospital, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia

Fortunately, the landscape of CLL treatment has dramatically transformed over the last ten years, shifting from chemotherapy to new targeted therapies. These advancements have not only extended patients’ lifespans but also often enhanced their quality of life. Consequently, many patients now undergo continuous treatment throughout their lives and frequently pass away from causes unrelated to CLL. At this year’s iwCLL, there was a debate and roundtable on how to define success in CLL. From a physician’s perspective, how is success in CLL treatment defined?

The debate and roundtable aimed to facilitate a discussion, allowing participants to exchange a wide array of viewpoints on the diversity in CLL treatment approaches and perspectives since there is not a ‘one-size-fits-all’ solution in this context. With years of experience in treating people with CLL, I have adopted a long-term approach. Recognizing the chronic nature of CLL, it is clear that the vast majority of patients will have to use various tools, hopefully, over several decades. My definition of success in CLL treatment aligns with long-term survival, but it is equally important to consider minimizing the cumulative burden of the disease and its treatments over time. Therefore, the goal is not just long-term survival, but achieving it with minimal adverse impact from the disease and its treatment.

Having delved into the physician’s perspective on the evolving landscape of CLL treatment and its implications for success, it becomes equally important to consider the other side of this equation. The patient’s experience and viewpoint are crucial in shaping our understanding of treatment effectiveness and quality of life. With this in mind, how do patients typically perceive their journey through CLL treatment, and what factors do they consider when defining success in their treatment and overall wellbeing?

One key observation in CLL treatment is the variability and evolution of patient perspectives. These viewpoints are uniquely personal and can shift significantly over time. For example, a patient might initially focus on a short-term goal, like being healthy for a significant family event, such as a daughter’s wedding. This goal serves as an immediate priority. However, once this short-term goal is achieved, their focus often shifts to longer-term objectives. This evolution in perspective is a natural and essential part of the patient’s journey. It is a patient’s right, as with all individuals, to reassess and modify their priorities over time. As clinicians, it is crucial to acknowledge these dynamics and support them. We should encourage open dialogue, inviting patients to continuously redefine what is most important to them at various stages of their treatment journey. Such a patient-centered approach ensures that we align treatment strategies with their evolving goals and preferences, thereby enhancing the overall effectiveness and relevance of the care we provide.

Reflecting on the individualized and dynamic nature of patient perspective in CLL treatment, we can see how crucial it is to align clinical objectives with patient-centered outcomes. This leads us to explore another vital dimension in the management of CLL. From a clinical scientist’s perspective, which study endpoints might reflect treatment success in CLL most accurately?

The quest to pinpoint the most effective study endpoints in CLL is where we have to make the biggest progress as a group. We recognize overall survival (OS) as an endpoint which all of the panelists agreed is of very high priority, but its measurement poses challenges due to its long-term nature. In the context of clinical trials or assessment of a single drug’s impact, OS becomes complex because it is influenced by the effectiveness of multiple treatments over time. Progression-free survival (PFS), which measures the duration of disease control, presents itself as a shorter key endpoint. However, its interpretation can be nuanced, particularly with intermittent treatments like venetoclax-obinutuzumab administered for 12 months. For instance, even if the disease reemerges post-treatment, it is often controllable with the same regimen, which leads to another phase of disease control. Therefore, the initial progression does not always signify the failure of a given therapy, nor does it account for the logistic or symptomatic burden on patients. Recently, there has been an excellent commission in Lancet Hematology that shed light on novel ways of accessing the global burden of treatment and symptoms of patients, both in terms of severity and persistence. For example, a single day of nausea differs significantly from enduring the same symptom persistently for months, yet both scenarios might be categorized as grade 1 nausea in clinical reports. Therefore, a refined approach to measuring overall symptom burden and incorporating ways of including the capacity to regain disease control are needed to develop more nuanced efficacy measures that go beyond OS and PFS. In conclusion, we have yet to establish an optimal measure for effectiveness in clinical trials for CLL, which underscores the need for ongoing research and development in this area.

Conducted by Anna Fenzl, PhD.

© 2023 Springer-Verlag GmbH, Impressum

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