Researchers characterized testing, treatment, and outcomes patterns among patients with chronic lymphocytic leukemia (CLL) receiving first-line therapy and found that novel targeted oral agents were increasingly used over time and produced better outcomes. Findings were presented via poster at the 63rd ASH Annual Meeting & Exposition.

“There have been many advances in CLL treatments over the past decade, with a number of novel agents targeting molecular pathways within CLL cells receiving approval from the US Food and Drug Administration,” authors wrote. 

The retrospective cohort study was conducted using real-world data from the Flatiron Health database and involved 280 cancer clinics, or approximately 800 sites of care, in the United States.

Researchers gathered data on 3654 participants. Patients were included if they were at least 18 years of age and initiated first-line therapy between December 2015 and December 2020, and excluded if they had participated in clinical trials or had other primary cancer diagnoses.

Participants were a median 70 years of age (range, 29-85), mostly male (64.3%), and mostly White (72.1%). “Approximately one-third (34.7%) of patients had Rai stage 0–I disease, 6.9% had stage II, 6.3% stage III, 11.5% stage IV, and 40.6% had undocumented Rai stage,” authors noted.

Most patients (n=3202, or 87.6%) received cytogenetic testing, florescence in situ hybridization, or IGHV mutation testing. Fewer tests were conducted in 2015-2026 compared to 2019-2020 for chromosome 17p deletion (36.1% vs 45.7%, respectively; P<.001) as well as for IGHV mutation (84.7% vs 89.2%, respectively; P=.003).

Among the full cohort, 1472 participants (40.3%) received IGHV mutation testing, the results of which indicated that 58.3% of patients had unmutated IGHV. Chromosome 17p deletion occurred in 11% of patients.

The ten most commonly used first-line treatments comprised 91.8% of all first-line treatments in the study. Treatments varied in utilization over time and included:

• ibrutinib;
• bendamustine, rituximab;
• rituximab;
• fludarabine, cyclophosphamide, rituximab;
• obinutuzumab, chlorambucil;
• obinutuzumab;
• obinutuzumab, venetoclax;
• ibrutinib, rituximab;
• chlorambucil;
• acalabrutinib;
• rituximab, cyclophosphamide, vincristine;
• ofatumumab, chlorambucil;
• fludarabine, rituximab; and
• rituximab, rituximab.

Among those who received the ten most commonly used treatments, 45.7% of patients underwent regimens that included novel targeted oral agents. Additionally, 33.4% of patients received chemoimmunotherapy (CIT) and 19.7% of patients received antiCD20 monotherapy. About a third (30%) of patients were given second-line treatment afterward.

“Evaluation of each 2-year period shows that treatment patterns for the top 10 [first-line] treatment regimens shifted, with use of novel targeted oral agents increasing from 27.1% (2015–2016) to 63.8% (2019–2020) (P<.001), while use of CIT and chemotherapy decreased over time,” authors wrote.

Median time to next treatment or death (TTNTD), which was estimated using Kaplan-Meier analysis, was 34.4 months for all patients and 36.5 months for patients who received the ten most common treatments over the course of the study period (n=3360).

Data also indicated that median TTNTD was:

• 47 months for patients who received novel targeted oral agents;
• 41.5 months for patients who received CIT (unadjusted P=.16);
• 43.9 vs 29.1 months for patients with chromosome 17p deletion who did or did not receive novel targeted oral agents, respectively; and
• 46.7 vs 37.2 months for patients with unmutated IGHV who did or did not receive novel targeted oral agents, respectively.

“As expected, the use of novel targeted oral agents increased over time, with a corresponding increase in TTNTD,” researchers concluded. “Clinical outcomes were improved in patients receiving novel targeted oral agents, both overall and in high-risk subgroups.”

Authors added that they intend to conduct further research evaluating TTNTD for novel targeted oral agents vs CIT, as well as patient outcomes after receiving different therapy sequences.

Reference:
Mato AR, Ravelo A, To TM, Schuldt R, Biondo JML. Real-world treatment patterns and outcomes of patients with chronic lymphocytic leukemia (CLL) receiving first-line therapy in the United States (US). Poster presented at: 63rd ASH Annual Meeting & Exposition; December 11-14, 2021: Atlanta, GA.