New Research Shows Real-World Track Record of Common CLL Therapies

A new study based on treatment of patients with chronic lymphocytic leukemia (CLL) in mostly community settings challenges earlier findings about the superiority of a common therapeutic approach and also makes a strong case for ibrutinib.

A new study offers real-world insights into the results of several common and emerging therapies for chronic lymphocytic leukemia (CLL), and suggests differences in how the drugs perform in community settings versus clinical trial settings.

The study, based on the Connect CLL registry, was published this month in Blood Advances. The registry enrolled 1494 patients with CLL who sought treatment at 199 healthcare centers in the US between the years 2010 and 2014. Most of the centers were community-based. Patients were grouped by line of therapy upon enrollment in the study, and the median follow-up was 46.6 months.

The most common treatments in the study were bendamustine and rituximab (BR), with just over one-third of patients receiving that therapy. Next was fludarabine, cyclophosphamide, and rituximab (FCR), which was given to 21.4% of patients. Rituximab monotherapy was prescribed in 18.5% of cases.

Median overall survival (OS) was not achieved in the first line of therapy; median OS was 63 months in the second line of therapy, and 38 months in the third or higher line of therapy.

In the first line of therapy, median event-free survival (EFS) was 59 months for patients on BR and 55 months in FCR. In a multivariate analysis, BR or FCR in the first line of therapy outperformed the other therapies in both OS and EFS. Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center, and colleagues noted that ibrutinib also had a positive impact, according to the data.

“As expected, EFS and OS became shorter and response rates decreased as LOT increased,” Mato and colleagues wrote. “In addition, ibrutinib therapy improved OS in all R/R [relapsed or refractory] patients regardless of the LOT in which it was received (LOT2, LOT3, or LOT≥4), even though it was approved by the FDA after the start of the Registry.”

The timing of the study period also meant that no patients in the study received ibrutinib in a frontline setting.

Pneumonia (11.6%) and febrile neutropenia (6.2%) were the most common adverse events.

The investigators used the data to identify a new category of patients at particularly high risk of death within 2 years of enrollment. The group was defined by a number of characteristics, including site of enrollment, race, age, insurance coverage, income, enrollment regimen, Charlson Comorbidity Index score, Eastern Cooperative Oncology Group Performance Status score at enrollment.

The analysis differed from some clinical trials in that it did not show a significant advantage for FCR over BR. The findings suggest that FCR’s advantages may not translate into community practice, Mato and colleagues said, adding that it might be due to less-rigorous use of the therapy in a real-world setting.

Though the treatment landscape evolved over the course of the study (and continues to evolve), the authors say the study has meaningful insights for clinicians as they make treatment recommendations.

“Receiving novel agents in LOT2 improved outcomes in patients who received previous CIT [chemoimmunotherapy], supporting the inclusion of ibrutinib, idelalisib, duvelisib, and venetoclax in the treatment paradigm for patients with R/R CLL,” they wrote. “However, additional randomized clinical trials and real-world data are needed to establish the role of non-CIT regimens in the treatment of patients with R/R CLL.”


Mato A, Nabhan C, Lamanna N, et al. The Connect CLL Registry: final analysis of 1494 patients with chronic lymphocytic leukemia across 199 US sites. Blood Adv 2020; 4(7):1407—1418. doi: 10.1182/bloodadvances.2019001145.