Dataset Information

Real-world Clinical Outcomes of First-Line Ibrutinib or Chemoimmunotherapy in Patients with Chronic Lymphocytic Leukemia by Risk Status.

ABSTRACT:

Introduction

Certain genetic features in chronic lymphocytic leukemia (CLL) are associated with inferior outcomes after chemoimmunotherapy (CIT). This retrospective study evaluated treatment patterns and clinical outcomes of patients with CLL, stratified into high-risk and non-high-risk groups, who received first-line ibrutinib or CIT therapy.

Methods

High-risk group included confirmed presence of del(17p), del(11q), unmutated IGHV, TP53 mutations, or complex karyotype. Weighted high-risk ibrutinib and CIT groups were compared for treatment effects using inverse probability of treatment weighting. Hazard ratios [95% CI] (HR) for time to next treatment (TTNT) were analyzed using Kaplan-Meier curves.

Results

Bendamustine/rituximab was the most common CIT regimen initiated for high-risk patients. During the available follow-up (median 34-35 months), 74.7% of the weighted high-risk ibrutinib group received only one line of treatment, compared with 47.2% of the weighted high-risk CIT group. The most common second-line treatment was ibrutinib for those in the CIT groups and venetoclax for the ibrutinib groups. The weighted high-risk ibrutinib group had a significantly longer TTNT (median not reached) than the weighted high-risk CIT group (median 34.4 months) and was 54% less likely to start a new treatment (HR 0.5 [0.3-0.6], P < 0.010). Among CIT-treated groups, high-risk patients had significantly shorter median TTNT than non-high-risk patients (P < 0.010). However, within the ibrutinib-treated groups, the median TTNT was similar between high-risk and non-high-risk patients (HR 2.2 [1.0-5.0]; P = 0.060).

Conclusion

This study found that first-line single-agent ibrutinib therapy was associated with significantly longer TTNT than CIT regimens in real-world patients with high-risk CLL. The results support the use of ibrutinib in high-risk patients. INFOGRAPHIC.

SUBMITTER: Huang Q

PROVIDER: S-EPMC9239963 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundData regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited.MethodsIn a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis.ResultsA total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (IGHV) mutation, ibrutinib-rituximab resulted in better progression-free survival than chemoimmunotherapy (90.7% vs. 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50). The 3-year progression-free survival among patients with IGHV mutation was 87.7% in the ibrutinib-rituximab group and 88.0% in the chemoimmunotherapy group (hazard ratio for progression or death, 0.44; 95% CI, 0.14 to 1.36). The incidence of adverse events of grade 3 or higher (regardless of attribution) was similar in the two groups (in 282 of 352 patients [80.1%] who received ibrutinib-rituximab and in 126 of 158 [79.7%] who received chemoimmunotherapy), whereas infectious complications of grade 3 or higher were less common with ibrutinib-rituximab than with chemoimmunotherapy (in 37 patients [10.5%] vs. 32 [20.3%], P<0.001).ConclusionsThe ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).

Project description:BackgroundStudies assessing ibrutinib's economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT.Materials and methodsOptum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted.ResultsTTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib's higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = -$10,615; P < .0001), yielding net savings (MMCD = -$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = -$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy.ConclusionDuring front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.