A significant subgroup of patients with both T2D and chronic lymphocytic leukemia (CLL) have unmet needs and an inferior prognosis.

Patients With CLL With Co-Occurring T2D Face Increase in Mortality

As the incidence of T2D is predicted to double during the next two decades, it is critical for hematologists to gain a better understanding of the relationship between T2D and chronic lymphocytic leukemia (CLL), explains Emelie Curovic Rotbain, MD, PhD. “Diabetes is one of the most common comorbid conditions with a prevalence of 8% to 21% at the time of CLL diagnosis,” Dr. Rotbain says. “The prevalence of diabetes is projected to double in the general population within the next two decades, partly due to an increasing incidence of  T2D.”

For a study published in the American Journal of Hematology, Dr. Rotbain and colleagues aimed to provide evidence on the survival outcomes of patients with co-occurring CLL and T2D, analyzing data from two of the world’s largest CLL cohorts: the Danish National Cohort (N=7,446) and the Mayo Clinic CLL Resources (N=3,069). A total of 60% and 68% of patients were male in the Danish and Mayo cohorts, respectively, while median age at CLL diagnosis was 71 and 64, respectively. Compared with patients without T2D, those with T2D tended to be male and older in both cohorts.

Infections Were Driving Force Behind an Increased Risk for Mortality

Using Cox proportional hazard regression analysis and Fine-Gray regression analysis, the primary outcomes were overall survival from time of CLL diagnosis, overall survival from time of CLL treatment, and time to first treatment, according to the study team,

In the Danish CLL cohort, the researchers observed that the prevalence of T2D was 11%, and 12% in the Mayo CLL cohort. Shorter overall survival was found in patients with CLL and T2D, from time of diagnosis and from first-line treatment. Compared with patients with CLL and without T2D, patients with both CLL and T2D were also less likely to receive treatment for CLL (Table). Infections were the driving force behind an increased risk for mortality, particularly in the Danish cohort.

Unmet Needs of Subgroup of Patients With Both CLL & T2D

“Our findings illustrate a poorer prognosis in patients [with CLL] with T2D, compared with patients without T2D, including an inferior overall survival both from CLL diagnosis and upon treatment for CLL,” Dr. Rotbain notes, adding that T2D presented an elevated risk for increased mortality due to causes of death both related and unrelated to CLL. Furthermore, “despite the increased risk for death due to CLL, patients with T2D were less likely to receive treatment for CLL and had a longer time until treatment,” Dr. Rotbain says. “These findings highlight a large subgroup of CLL patients with an inferior prognosis and a possible unmet treatment need.”

While limited treatment options and poor prognoses exist for some comorbid conditions, treatment for T2D has advanced considerably over the past decade, Dr. Rotbain points out. “New treatment agents, such as SGLT2-inhibitors and GLP1-analogs, have displayed survival benefits and lower risk for diabetes-related complications in combination with first-line treatment with metformin in T2D. Few patients with CLL require treatment upfront upon diagnosis, thus we have the possibility to optimize the treatment for T2D before initiating CLL treatment. Further studies are required to investigate whether this can contribute to increased tolerability and survival upon CLL treatment.

These findings, Dr. Rotbain concludes, “emphasize unmet needs and an inferior prognosis in a substantial subgroup of CLL patients with co-occurring T2D. As this patient group is projected to increase significantly in the coming years, additional interventions will be required, including awareness of possible undertreatment.”