KEY TAKEAWAYS
- The Phase 3 trial’s primary aim was to compare the effectiveness of(IR therapy to FCR in patients with previously untreated CLL aged 70 or younger.
- The study involved a random assignment of 529 patients in a 2:1 ratio to receive either IR or six cycles of FCR.
- The continuous administration of ibrutinib therapy was well-tolerated for more than five years in most patients with CLL.
- IR therapy significantly improved PFS compared to FCR, with a hazard ratio HR of 0.37 and a P<0.001.
- IR therapy provides better PFS and OS than FCR therapy in CLL patients.
- The long-term tolerability of continuous ibrutinib therapy in most CLL patients exceeded 5 years.
In this study, researchers presented the extended monitoring of the randomized E1912 clinical trial, which compared the enduring effectiveness of ibrutinib-rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR). Additionally, researchers described the capacity for continuous ibrutinib treatment. The clinical trial E1912 recruited 529 individuals who were previously untreated and aged 70 years or younger, all of whom were diagnosed with chronic lymphocytic leukemia (CLL). The study participants were subjected to a random assignment process, wherein they were allocated in a 2:1 ratio to receive either IR or six cycles of FCR. Based on a median follow-up duration of 5.8 years, the median progression-free survival (PFS) is significantly better for the IR group, with a hazard ratio (HR) of 0.37 and a P< 0.001. IR has demonstrated an improvement in progression-free survival compared to FCR in patients diagnosed with both mutated and unmutated immunoglobulin heavy chain variable region (IGHV) gene chronic lymphocytic leukemia. The hazard ratio for mutated CLL was 0.27 with a P<0.001, while the HR for unmutated CLL was also 0.27 with a P< 0.001. Out of the 354 patients who were randomized to receive intervention, 214 (60.5%) continue to administer ibrutinib.
Out of the 138 patients who underwent interventional radiology treatment, 37 patients (10.5% of the total number of patients who initiated IR) discontinued the therapy due to disease progression or mortality. Additionally, 77 patients (21.9% of the total number of patients who started IR) discontinued the treatment due to adverse events (AEs) or complications. In comparison, 24 patients (6.8% of those who began IR) withdrew from the therapy for other reasons. Disease progression was infrequent among patients who could maintain their treatment with ibrutinib. The median duration between discontinuation of ibrutinib and the occurrence of disease progression or mortality in patients who ceased treatment due to reasons other than progression was 25 months. A consistent enhancement in the survival rate of patients was noted in the intervention group (hazard ratio, 0.47; P = .018) concerning overall survival (OS).
The study showed that infrared therapy provided better progression-free survival than fludarabine, cyclophosphamide, and rituximab therapy in patients with chronic lymphocytic leukemia with either mutated or unmutated immunoglobulin heavy chain variable region genes. Additionally, infrared therapy also offered superior overall survival. The administration of ibrutinib therapy continuously has been well-tolerated for a period exceeding 5 years in most patients diagnosed with chronic lymphocytic leukemia.
Source:https://pubmed.ncbi.nlm.nih.gov/35427411/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02048813
Shanafelt TD, Wang XV, Hanson CA, Paietta EM, O’Brien S, Barrientos J, Jelinek DF, Braggio E, Leis JF, Zhang CC, Coutre SE, Barr PM, Cashen AF, Mato AR, Singh AK, Mullane MP, Little RF, Erba H, Stone RM, Litzow M, Tallman M, Kay NE. Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial. Blood. 2022 Jul 14;140(2):112-120. doi 10.1182/blood.2021014960. PMID: 35427411; PMCID: PMC9283968.
