For older adults with relapsed follicular lymphoma (FL) or chronic lymphocytic leukemia (CLL), idelalisib may be associated with higher rates of dose reduction and toxicity than reported in clinical trials, according to results of a study published in JAMA Oncology (online December 19, 2019; doi:10.1001/jamaoncol.2019.3994).

The P13K inhibitor idelalisib is approved as a monotherapy in relapsed FL and in combination with rituximab for relapsed CLL. Prior research has shown that adverse events associated with idelalisib may be severe and treatment-limiting. Outcomes in a real-world population have yet to be characterized.

Steven T Bird, PhD, PharmD, MS, office of pharmacovigilance and epidemiology, US Food and Drug Administration, and colleagues designed a cohort study to compare idelalisib treatment outcomes in the clinical setting with outcomes in clinical trial data. The study compared clinical trial participants aged at least 65 years from studies 101-09 and 312-01126 with Medicare beneficiaries of the same disease state and treatment regimen.

Study 101-09 was a phase II trial that supported accelerated approval of idelalisib for relapsed or refractory FL. Study 312-0116 was a phase III trial that supported approval of idelalisib plus rituximab for relapsed CLL.

Researchers sampled 26 trial participants and 305 Medicare beneficiaries who received idelalisib for FL, as well as 89 trial participants and 294 Medicare beneficiaries who received idelalisib plus rituximab for CLL.

Results of the comparison showed that when compared with trial participants, Medicare beneficiaries were older with higher comorbidity, had a shorter median treatment duration for CLL but not for FL, a numerically higher mortality rate, a significantly higher fatal infection rate per 100 person-years for CLL, and a numerically higher fatal infection rate per 100 person-years for FL.

Additionally, Dr Bird and colleagues found that trial participants had approximately twice as many dose reductions that Medicare beneficiaries across both disease types. A hospitalized infection within 6 months prior to idelalisib initiation was associated with a 2.11-fold increased risk for on-treatment fatal infections among Medicare beneficiaries, they added.

In their conclusion, authors of the study wrote that, “Selective eligibility criteria and closer monitoring of trial patients may be responsible for limited generalizability of trial data to clinical practice.”—Zachary Bessette