Results from a study comparing outcomes of patients treated with idelalisib in clinical trials versus the clinical setting show less favorable outcomes in the clinical setting (JAMA Onc. 2019 Dec 19. Epub ahead of print).

Although idelalisib monotherapy is approved for the treatment of relapsed follicular lymphoma (FL) and combined with rituximab for the treatment of relapsed chronic lymphocytic leukemia (CLL), the toxic effects of these drugs can be severe and treatment-limiting, explained Steven T. Bird, MD, PhD, PharmD, MS, Office of Pharmacovigilance and Epidemiology, FDA, Silver Spring, Maryland, and colleagues.

Noting a lack of outcomes characterization for patients treated with idelalisib in the clinical setting, Dr Bird et al conducted a cohort study comparing these patients with those treated in clinical trials.

The cohort study included 115 patients who participated in clinical trials 101-09 and 312-0116 and 599 Medicare beneficiaries treated with idelalisib in the clinical setting.

Study 101-09 was a phase 2, single-group, open-label trial evaluating idelalisib in relapsed or refractory FL and 312-0116 was a phase 3, multi-center, double-blind trial evaluating idelalisib plus rituximab in relapsed CLL.

The primary end points of the cohort study included treatment duration, mortality during treatment and overall, and serious and fatal infections between patients in the trial and clinical settings.

Of the 115 clinical trial participants, 26 received idelalisib for FL and 89 received idelalisib plus rituximab for CLL. Of the 599 Medicare beneficiaries, 305 received idelalisib for FL and 294 received idelalisib plus rituximab for CLL.

Overall, Medicare beneficiaries were older, had more comorbidities, and had a shorter median treatment duration for CLL but not FL than clinical trial participants (CLL, 173 days vs 473 days, respectively; P <.001 and FL, 114 days vs 160 days, respectively; P = .38). Additionally, Medicare beneficiaries had a higher mortality rates than those in clinical trials (CLL: HR, 1.40; 95% CI, 0.93-2.11 and FL: HR, 1.39; 95% CI, 0.69-2.78); the same was seen with fatal infection rates per 100 person-years for CLL (18.4 in trials vs 9.8 in clinics; P = .04) and FL (27.6 vs 18.6, respectively; P = .54).

Furthermore, trial participants had approximately twice as many dose reductions as Medicare beneficiaries in the clinical setting for CLL (32.6% vs 18.0%, respectively; P = .003) and FL (38.5% vs 16.1%, respectively; P= .02).

Dr Bird and colleagues noted that a hospitalized infection within 6 months of idelalisib therapy initiation was associated with a 2.11-fold increased risk for fatal infections during treatment (95% CI, 1.44-3.10) among Medicare beneficiaries.

“We observed substantial imbalances in baseline comorbidities and treatment outcomes between Medicare beneficiaries and trial participants aged 65 years or older,” Dr Bird and colleagues said.

“Immunosuppression-related toxic effects, including infections, may have been somewhat reduced in trials by more frequent dose reductions and exclusion of patients with ongoing infections. Selective eligibility criteria and closer monitoring of trial patients may be responsible for limited generalizability of trial data to clinical practice,” they concluded.—Janelle Bradley