Study Examines Trends in Real-World Treatment Sequencing Patterns for CLL

The availability of B-cell receptor inhibitors (BCRis) and other novel agents for the treatment of chronic lymphocytic leukemia (CLL) has reshaped the treatment paradigm for the disease, with 87% of patients receiving a novel agent, according to interim findings from the ongoing CLL Collaborative Study of Real-World Evidence, or CORE. Ibrutinib was the most prescribed agent, followed by venetoclax and idelalisib.

Anthony R. Mato, MD, MSCE, from Memorial Sloan Kettering Cancer Center in New York, presented findings from CORE at the 2019 ASH Annual Meeting. “The treatment paradigm is evolving with the introduction of novel agents,” Dr. Mato said. “Results from this study will provide a baseline description of treatment sequence patterns enabling clinicians to benchmark the impact of the introduction of novel agents and associated outcomes.”

This retrospective, multicenter, collaborative observational study collects real-world data about the therapies and outcomes of patients with CLL/small lymphocytic lymphoma (SLL) who were treated at community or academic sites between 2012 and 2018. In this analysis, researchers looked specifically at patients who began treatment for CLL/SLL in the relapsed/refractory setting after February 12, 2014, when the first novel agent was approved by the U.S. Food and Drug Administration.

Dr. Mato presented interim data on treatment sequencing patterns for 267 adult patients. At the time of interim analysis, 231 patients (87%) received a novel agent in at least one line of therapy, although it was most commonly used as a second line of therapy:

  • first: 35 (15%)
  • second: 133 (58%)
  • third or later: 63 (27%)

Ibrutinib was the most used agent in the first line setting (n=198; 86%), followed by venetoclax (n=18; 8%) and idelalisib (n=12; 5%).

Looking at the sequencing patterns of the enrolled patients, researchers observed that more than half of patients (n=143; 54%) received chemotherapy/chemoimmunotherapy (CT/CIT) followed by a novel agent. It also was common for patients to receive a novel agent followed by a novel agent (n=63; 24%) or a novel agent followed by CT/CIT (n=17; 7%).

Despite the uptake of novel agents, 18% of patients (n=47) were only treated with CT/CIT.

Next, to examine how patients responded to specific agents and sequences, the investigators compared outcomes for the 220 patients (82%) who had received BCRi-based therapy and venetoclax-based regimens (n=62; 23%). Again, in each of these groups, most had received novel agents as their secondline therapy.

Among those who received BCRi-based regimens, 50 (23%) achieved complete remission (CR) and 83 (38%) achieved partial remission (PR). Eighty-eight patients (40%) received a subsequent therapy, the most common of which was a venetoclax-containing regimen (n=34; 39%). Forty-six patients achieved a CR or PR to their subsequent therapy.

Of the 62 patients who received venetoclax-based regimens first, 20 (32%) achieved CR and 14 (23%) achieved PR. Fifteen patients (24%) received a subsequent therapy, typically a BCRi-containing regimen (n=10; 67%); 7 patients responded (3 CRs and 4 PRs).

The data from this analysis are still early, Dr. Mato noted, and researchers are continuing to collect data to better understand real-world treatment of CLL/SLL.

The authors report relationships with AbbVie and other pharmaceutical companies.


Mato AR, Sail K, Yazdy MS, et al. Treatment sequences and outcomes of patients with CLL treated with venetoclax and other novel agents post introduction of novel therapies. Abstract #1756. Presented at the 2019 American Society of Hematology Annual Meeting, December 7, 2019; Orlando, FL.