Disease Flare During Temporary Interruption of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia

The oncologist

article

Paul J. Hampel¹  Amber B. Koehler¹  Amie L. Fonder¹  Susan M. Schwager¹  Daniel L. Van Dyke²  Esteban Braggio³  Susan L. Slager⁴  Neil E. Kay¹  Sameer A. Parikh¹  Timothy G. Call¹  Kari G. Rabe⁴  Wei Ding¹  Eli Muchtar¹  Saad S. Kenderian¹  Yucai Wang¹  Jose F. Leis³  Thomas E. Witzig¹ 

[1] Division of Hematology, Department of Medicine, Mayo Clinic;Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic;Department of Hematology and Oncology, Mayo Clinic;Division of Biomedical Statistics & Informatics, Department of Health Sciences Research, Mayo Clinic

关键词: B-cell chronic lymphocytic leukemia;    Ibrutinib;    Drug therapy;    Flareup;   

DOI  :  10.1634/theoncologist.2020-0388

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Approximately 25% of patients with chronic lymphocytic leukemia (CLL) experience a flare of disease following ibrutinib discontinuation. A critical question is whether this phenomenon may also occur when ibrutinib is temporarily held. This study aimed to determine the frequency and characteristics of disease flares in this setting and assess risk factors and clinical outcomes. Materials and Methods We identified all patients with CLL seen at Mayo Clinic between October 2012 and March 2019 who received ibrutinib. Temporary interruptions in treatment and associated clinical findings were ascertained. Results Among the 372 patients identified, 143 (38%) had at least one temporary interruption (median 1 hold, range 1–7 holds) in treatment. The median duration of interruption was 8 days (range 1–59 days) and the most common indication was periprocedural. Among the 143 patients with ≥1 hold, an associated disease flare was seen in 35 (25%) patients: mild (constitutional symptoms only) in 21 patients and severe (constitutional symptoms with exam/radiographic findings or laboratory changes) in 14 patients. Disease flare resolved with resuming ibrutinib in all patients. Predictive factors of disease flare included progressive disease at time of hold and ≥ 24 months of ibrutinib exposure. The occurrence of disease flare with an ibrutinib hold was associated with shorter event-free survival (hazard ratio 2.3; 95% confidence interval 1.3–4.1; p = .007) but not overall survival. Conclusion Temporary interruptions in ibrutinib treatment of patients with CLL are common, and one quarter of patients who held ibrutinib in this study experienced a disease flare. Resolution with resuming ibrutinib underscores the importance of awareness of this phenomenon for optimal management. Implications for Practice Ibrutinib is a very effective treatment for chronic lymphocytic leukemia (CLL) but needs to be taken continuously. Side effects, such as increased bleeding risk with procedures, require temporary interruptions in this continuous treatment. Rapid CLL progression following ibrutinib discontinuation has been increasingly recognized. This study demonstrates that similar flares in disease signs or symptoms may occur during ibrutinib holds as well. Importantly, management with restarting ibrutinib led to quick clinical improvement. Awareness of this phenomenon among clinicians is critical to avoid associated patient morbidity and premature cessation of effective treatment with ibrutinib if the flare is misidentified as true progression of disease.

【 授权许可】

CC BY|CC BY-NC