Targeted Therapies for CLL Can Lead to Improved Patient Outcomes

The proliferation of targeted therapies, such as ibrutinib and venetoclax, to treat patients with chronic lymphocytic leukemia (CLL) has led to improved patient outcomes and a transformed treatment landscape in Germany, which can provide a roadmap for improving outcomes in the US and elsewhere, according to a study published in ejHaem.¹

Over the past 2 decades, there has been a prolific expansion of treatment options for CLL. These include the widespread adoption of chemoimmunotherapy and the recent approval of signaling pathway inhibitors such as ibrutinib and venetoclax.

Using real-world data analysis, the investigators sought to analyze CLL treatment patterns from over a decade of claims data in Germany, with the goal of discerning a shift in survival outcomes among patients.

Included in the study were 1040 individuals—684 male patients and 356 female patients—who initiated first-line therapy between 2011 and 2022. The investigators examined 4 types CLL treatments: CD20-antibody monotherapy, chemotherapy, chemoimmunotherapy, and targeted therapy.

Analysis of overall survival (OS) was key to the study. For first-line therapy, the median OS was 11 years; among the female patients this was not reached, while it was 10 years among the male patients. Prior to 2016, the median OS for diagnosed patients was 9 years, and after 2016, the analyzed patients did not reach the median OS during the study period (P < .001). There was a significantly better OS for patients diagnosed in or after 2016 (HR, 0.56; 95% CI, 0.44-0.69), according to the investigators.

Most notable among the observed patterns was the large increase in use of targeted therapy for refractory disease (RD). After starting at 11% in 2014, use of the practice in 2016 matched the 72% rate seen for chemoimmunotherapy at its peak, before exceeding that and peaking at 81% in 2019; the rate then stabilized, the investigators found.

Additionally, the 5 most prevalent first-line and RD regimens for CLL—both prior to and after the approval of ibrutinib in 2016—were analyzed. Regarding first-line treatments, bendamustine and rituximab led in the beginning of the 2010s, but were passed by ibrutinib and venetoclax plus obinutuzumab (VO) following 2016 as the targeted therapy gained prominence.

The results of the current analysis are consistent with previous studies on overall survival based on registry data. | Image Credit: Mopic - stock.adobe.com

For RD therapy, rituximab’s prevalence in 2011 was surpassed by ibrutinib in 2016. Venetoclax monotherapy or venetoclax plus rituximab combination therapies soon took the lead in prescriptions for patients in 2021, according to the investigators.

To get a better understanding of the effects of different treatments on individuals, the investigators examined the duration of each treatment. The investigators found that the median (IQR) time of treatment for CD20 monotherapy was 154.5 (163.5) days vs 122 (289) days for chemotherapy, 176 (41) days for chemoimmunotherapy, and 373 (485.75) days for targeted therapy.

Furthermore, ibrutinib and VO were found to be the 2 most prescribed regimens among targeted therapies, with median durations of 630 (838.25) days and 308 (176.5) days, respectively.

The results of the current analysis are consistent with previous studies on OS based on registry data. In an analysis of over 11,000 patients with CLL over 5 decades in Sweden, investigators found significant improvement in survival for the entire study population, likely due to the proliferation of new and more effective drugs.²

Results of studies undertaken in Europe and North America regarding therapy usage rates are similar, although there were some important differences. One study conducted by Huang et al that focused on British Columbia found the most prevalent first-line therapy between 2014 and 2015 was fludarabine plus rituximab.³ Interestingly, this wasn’t among the top 5 in the current study.

They also found that ibrutinib usage for first-line therapy was much higher in 2016 than in their current study—18.7% compared with 10%—which suggests a faster rate of adoption vs Germany. These differences highlight the need for ongoing analysis of CLL treatment options.

Overall, there is no denying the reshaping of the treatment landscape for CLL in Germany and the strong treatment protocols in place that have led to positive outcomes.

“The observed favorable OS outcome in patients commencing treatment during the widespread adoption of ibrutinib-based therapies underscores the marked improvement in CLL management attributed to these targeted treatments,” the investigators concluded.

References

1. Wartmann H, Kabilka A, Deiters B, Schmitz N, Vollmer T. A decade of chronic lymphocytic leukemia therapy in Germany: real-world treatment patterns and outcomes (2010-2022). ejHaem. 2024;5(2):346-352. doi:10.1002/jha2.888.

2. Kristinsson S, Dickman P, Wilson W, Caporaso N, Björkholm M, Landgren O. Improved survival in chronic lymphocytic leukemia in the past decade: a population-based study including 11,179 patients diagnosed between 1973-2003 in Sweden. Haematologica. 2009;94(9):1259-1265. doi:10.3324/haematol.2009.007849.

3. Huang SJ, Gerrie AS, Young S, et al. Comparison of real-world treatment patterns in chronic lymphocytic leukemia management before and after availability of ibrutinib in the province of British Columbia, Canada. Leuk Res. 2020;91:106335. doi:10.1016/j.leukres.2020.106335.