Real-World Data on First-Line Ibrutinib or Chemoimmunotherapy Outcomes in CLL By Risk Status

The prognosis for high-risk (HR) chronic lymphocytic leukemia (CLL) is poor. Clinical data have found that small molecular inhibitor (SMI) therapies outperform chemoimmunotherapy (CIT) in patients with CLL, but CIT is still often chosen for HR and non-HR patients with CLL in real-world practice. A study assessing treatment patterns and time to next treatment (TTNT) in HR and non-HR patients with CLL undergoing ibrutinib (IBR) or CIT as first-line therapy was presented at the 62nd ASH Annual Meeting & Exposition.

Medical records for adult HR and non-HR patients with CLL were obtained from 40 clinical practices (68% community and 32% academic). All patients initiated first-line single-agent IBR or CIT (index date) between February 14, 2014, and December 31, 2016. Patients with del(17p), del(11q), TP53 mutation, unmutated immunoglobulin heavy chain variable, or complex karyotype (≥3 chromosomal abnormalities) at the time of first-line treatment initiation were considered HR. Patients with testing-confirmed absence of the HR-associated factors were considered non-HR. To evaluate TTNT, Kaplan-Meier (KM) and Cox-proportional hazards regression analyses were implemented to compare IBR HR versus CIT HR, CIT HR versus CIT non-HR, and IBR HR versus IBR non-HR. Inverse probability treatment weighting was used to level out baseline characteristics between the two HR groups.

Final analysis consisted of 516 CLL patients, of whom 271 were HR (IBR, n=175; CIT, n=96) and 245 were non-HR (IBR, n=82; CIT, n=163).

When assessing the HR patients, the median duration of first-line therapy for the IBR patients was 28.6 months (range, 1-58.1 months) versus 5.5 months (range, 0.5-38.4 months) for the CIT patients; median follow-up duration was 33.3 months (range, 1.4-58.5 months) and 35.3 months (range, 1.3-59.5 months), respectively.

Upon KM analysis, median TTNT was significantly longer for the weighted IBR HR patients compared with CIT HR patients; they were also 54% less likely to initiate a new treatment (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.34-0.62; P<0.01).

When comparing HR versus non-HR patients who received CIT, HR patients had a much shorter median TTNT and were more than twice as likely to start a new treatment (HR, 2.43; 95% CI, 1.58-3.47; P<0.01). TTNT did not largely differ between the IBR HR versus non-HR patients (median TTNT not reach; HR, 2.2; 95% CI, 0.96-4.96; P=0.06).

When assessing the available follow-up, weighted IBR HR patients, compared with weighted CIT HR patients, were more likely to have only had one line of treatment (74.7% vs. 47.2%), as were CIT non-HR patients compared with CIT HR patients (69.9% vs. 45.8%) and IBR non-HR patients versus IBR HR patients (91.5% vs. 81.7%). Most patients received SMI therapy as second-line treatment.