The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials

Abstract

Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL), assessed on and after treatment, correlates with increased progression-free and overall survival benefit. More recently, MRD assessment has been included in large clinical trials as a primary outcome and is increasingly used in routine practice as a prognostic tool, a therapeutic goal, and potentially a trigger for early intervention. Modern therapy for CLL delivers prolonged remissions, causing readout of traditional trial outcomes such as progression-free and overall survival to be inherently delayed. This represents a barrier for the rapid incorporation of novel drugs to the overall therapeutic armamentarium. MRD offers a dynamic and robust platform for the assessment of treatment efficacy in CLL, complementing traditional outcome measures and accelerating access to novel drugs. Here, we provide a comprehensive review of recent major clinical trials of CLL therapy, focusing on small-molecule inhibitors and monoclonal antibody combinations that have recently emerged as the standard frontline and relapse treatment options. We explore the assessment and reporting of MRD (including novel techniques) and the challenges of standardization and provide a comprehensive review of the relevance and adequacy of MRD as a clinical trial endpoint. We further discuss the impact that MRD data have on clinical decision-making and how it can influence a patient’s experience. Finally, we evaluate how upcoming trial design and clinical practice are evolving in the face of MRD-driven outcomes.

Monitoring Response and Resistance to Treatment in Chronic Lymphocytic Leukemia

“…MRD analysis in CLL clinical trials has been recently reviewed [ 11 ], being a secondary end-point in several clinical trials or even a primary end-point [ 12 ].…”

PD-1 and LAG-3 as early prognostic markers in the treatment of patients with chronic lymphocytic leukemia

“…Технология выявления остаточных клональных злокачественных клеток эво люционировала наряду со своей номенклатуройот «остаточной болезни» к «минимальной остаточной болезни» до термина «измеримая остаточная болезнь», установленного Международным руководящим коми тетом (ISC) по МОБ ХЛЛ [5]. Величина остаточной болезни при ХЛЛ, оцениваемая во время и после ле чения, измеряема и используется в рутинной практи ке в качестве прогностического инструмента, терапев тической цели и потенциального триггера для раннего вмешательства [6]. Остаточная популяция опухолево го клона ХЛЛ в крови в количестве <0,01 % является предиктором высокой вероятности длительной ремис сии более 5 лет.…”