Early Disease Progression Predicted Worse Survival in CLL

Disease progression within 2 years of treatment initiation for chronic lymphocytic leukemia (CLL) was a robust clinical prognostic factor for inferior overall survival among patients treated with chemoimmunotherapy, according to the results of a study published in Blood Advances.

“In view of the clonal heterogeneity and evolution of CLL, early progression of disease indicates the presence of CLL clones capable of surviving treatment and leading to disease progression,” wrote Inhye E. Ahn, MD, of the National Cancer Institute, and colleagues. “Early progression of disease may function as a posttreatment risk stratification tool and a robust clinical endpoint, which should be further explored in the context of targeted agents.”

According to the study, treatment of CLL with chemoimmunotherapy promotes clonal evolution of aggressive clones, which may lead to early progression of disease. To evaluate the prognostic value of early progression, the researchers studied 829 patients with CLL from the Connect CLL Registry between 2010 and 2014. All patients were receiving first-line therapy and were classified as either early progression of disease (less than 2 years after treatment initiation), late progression (2 years or later), or no progression.

With a median follow-up of about 4 years, about one-quarter of the patients (25.2%) had early progression, 19.5% had late progression, and 55.3% had no disease progression. Those patients with early disease progression were older and had inferior response to similar first-line treatment regimens compared with patients with late or no disease progression. The overall response rate was 53% for patients with early progression compared with 80% for late progression and 84% for no progression.

In addition, about one-third (34%) of patients with early progression had unfavorable risk cytogenetics compared with only 20% of patients with no progression (P = .04).

Patients with early progression had worse overall survival across all patients (hazard ratio [HR], 3.6; 95% CI, 2.6–5.1; P < .01) and among those treated with fludarabine, cyclophosphamide, and rituximab (FCR), as well as those treated with bendamustine plus rituximab (BR) (P < .05). Worse overall survival was also independently associated with high comorbidity index, ages of 75 or older, Rai stage II or greater, and treatment duration of 4 months or less.

The researchers identified several factors associated with early progression, including ages of 75 or older, presence of del(17p), first-line therapy other than FCR or BR, and a treatment duration of 4 months or less (P < .01 for all).

“Time to progression of disease may potentially serve as a posttreatment risk stratification tool that offers a simple readout of clonal fitness in the context of first-line treatment without the need for additional sophisticated or costly genomic analyses,” the researchers wrote. “Current risk stratification of CLL heavily uses pretreatment factors. … If we use time to progression as a prognostic factor, patients who progress within 2 years of starting first-line therapy with conventional chemotherapy regimens can be prioritized for clinical trials of highly active targeted agents, in combination or in sequence, rather than being treated with conventional approaches using chemoimmunotherapy or a single-agent kinase inhibitor.”