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Jennifer R. Brown, MD, PhD


Umbrella Analysis of B-Cell Therapies for Chronic Lymphocytic Leukemia

By: Lauren Harrison, MD, MS
Posted: Thursday, June 30, 2022

An umbrella analysis of the most recent therapies for B-cell chronic lymphocytic leukemia (CLL) showed an increase in progression-free survival but not overall survival. Based on these findings, Monia Marchetti, MD, of Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Asti, Italy, and colleagues recommended customizing treatment choices to each patient in their article, published in the Journal of Clinical Medicine.

This study reviewed 17 meta-analyses and network meta-analyses published in the past 5 years that compared pharmacologic therapies for CLL. Patients in these studies had either relapsed or refractory disease or had never been treated for their cancer. Details regarding overall survival, progression-free survival, and safety from these meta-analyses were compiled into this umbrella analysis.

In patients with relapsed and refractory disease, novel treatments such as Bruton’s tyrosine kinase (BTK) inhibitors and B-cell lymphoma-2 (BCL2) inhibitors yielded progression-free survival hazard ratios of 0.08 to 0.24 when compared with chemotherapy. These drugs also led to an advantage in overall survival, with hazard ratios between 0.20 and 0.58 compared with standard chemotherapy. Among patients who had never been treated for their CLL, the progression-free survival hazard ratios for four different obinutuzumab- and/or acalabrutinib-based therapies ranged from 0.11 to 0.61. However, there was no significant advantage for these treatments over standard therapy in terms of overall survival.

There were 10 meta-analyses that compared the safety outcomes of various therapies for CLL. There was a considerable increased risk of infections among patients who received BTK inhibitors (odds ratio = 1.24) for their relapsed or refractory disease compared with those who received the standard of care. In addition, abdominal adverse events, arthralgia, any-grade bleeding, hypertension, and atrial fibrillation occurred more often in patients receiving ibrutinib for treatment of their relapsed/refractory or never-treated CLL. Therefore, these newer medications were noted to minimally decrease safety.

Disclosure: For Dr. Marchetti’s disclosures, visit The remaining authors reported no conflicts of interest.

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