Clinical Trial Participants vs. Medicare Beneficiaries Receiving Idelalisib: An Outcomes Analysis

A new study compared outcomes between relapsed follicular lymphoma and relapsed chronic lymphocytic leukemia patients treated with idelalisib in the clinical setting versus clinical trial data.

“Idelalisib (IDEL) is approved as monotherapy in relapsed follicular lymphoma (FL) and with rituximab (IDEL+R) for relapsed chronic lymphocytic leukemia (CLL). Toxic effects can be severe and treatment-limiting. Outcomes in a real-world population are not yet characterized,” the researchers wrote.

The cohort study included clinical trial patients aged 65 years or older in studies 101-09 and 312-0116 against Medicare beneficiaries in the same disease state receiving the same treatment regimen. Study 101-09 was a phase 2, single-group, open-label trial of refractory follicular lymphoma patients receiving idelalisib, while study 312-0116 was a phase 3, multicenter, randomized, double-blind trial of relapsed chronic lymphocytic leukemia patients receiving idelalisib plus rituximab. Data analyses took place between February and December 2018. The main outcomes were treatment duration, on-treatment and overall mortality, and serious and fatal infections.

Final analysis included 26 trial participants (mean [SD] age, 73 [4.9] years; 46.2% were female) and 305 Medicare beneficiaries (mean [SD] age, 76 [6.9] years; 54.8% were female) receiving idelalisib for follicular lymphoma and 89 trial participants (mean [SD] age, 74 [6.0] years; 33.7% were female) and 294 Medicare beneficiaries (mean [SD] age, 76 [6.3] years; 37.8% were female) receiving idelalisib plus rituximab for relapsed chronic lymphocytic leukemia. Medicare beneficiaries, compared to trial participants, tended to be older and have more comorbidities, shorter median treatment duration for chronic lymphocytic leukemia (173 days vs. 473 days), higher mortality rate (chronic lymphocytic leukemia, hazard ratio[HR]=1.40; 95% confidence interval [CI], 0.93-2.11; follicular lymphoma, HR=1.39; 95% CI, 0.69-2.78), and higher fatal injection rate for 100 person-years for chronic lymphocytic leukemia (18.4 vs. 9.8) and numerically higher rate for follicular lymphoma (27.6 vs. 18.6). trial participants had more dose reductions (chronic lymphocytic leukemia, 32.6% vs. 18.0%; follicular lymphoma, 38.5% vs. 16.1%). Medicare beneficiaries hospitalized for infection within the six-month period preceding idelalisib treatment initiation had a 2.11-fold higher likelihood for fatal infections during treatment.

The study was published in JAMA Oncology.

“We observed substantial imbalances in baseline comorbidities and treatment outcomes between Medicare beneficiaries and trial participants aged 65 years or older,” the authors concluded. “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.”