Evidence Rating Level: 2 (Good)
1. Combination therapy of Ibrutinib and Venetoclax may be successful first-line treatments for patients with Chronic Lymphocytic Leukemia (CLL) who are currently not undergoing treatment
2. This combination therapy had a 3-year progression free survival (PFS) of 93% in first line treatment of CLL
The evolution and treatment of chronic lymphocytic leukemia (CLL) presents a clinical burden on the healthcare system causing a need for treatment plans to rapidly evolve in order to control the condition. The main form of treatment has shifted away from chemoimmunotherapy and towards oral targeted medications. However, success rates and durability of CLL treatment requires further research, particularly when comparing monotherapy to combined therapies. This study looked specifically at Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor as well as Venetoclax, a Bcl-2 inhibitor. These drugs have been used primarily in monotherapy leading to partial but not full remission of CLL. This nonrandomized phase 2 trial aimed to better understand the synergy of the two drugs by assessing remission and durability of CLL when combining the two medications. The study did this by assessing the measurable residual disease (MRD) in patients taking these medications together. While patients underwent cycles of treatment, this MRD was monitored in the bone marrow using peripheral blood samples taken every 6 months. More specifically, the study was a phase 2, non randomized trial conducted with patients currently not undergoing CLL treatment. The participants in the study had either del(17p), TP53-mutated CLL, del(11q), unmutated immunoglobulin heavy chain variable gene, or were aged 65 or older. In total, 75 patients taking combination therapy of Ibrutinib and Venetoclax were included in the study between August 2016 and June 2018. Serial assessments of their bone marrow were performed to achieve undetectable MRD remission (U-MRD). Overall, 75% of the baseline cohort (n=60) reached U-MRD remission during the study period. Furthermore, the estimated 3-year progression free survival (PFS) rate was 93% (95% CI, 88%-99%) with an overall survival rate of 96% (95% CI, 92%-100%). While patients had variable outcomes, remission rates and PFS rates, the study found that no participants had CLL progression while taking the combined therapy. The study results focused on the impact of the combined therapy on CLL, however it is worth noting that participants had side effects, adverse events, complications, and one possible treatment-associated death was reported. Overall, this study reveals that further research is required to better understand the long-term effects of combined treatment with Ibrutinib and Venetoclax as this study had a relatively short follow up period of only 38.5 months.
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