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Original Investigation
December 19, 2019

Idelalisib for Treatment of Relapsed Follicular Lymphoma and Chronic Lymphocytic Leukemia: A Comparison of Treatment Outcomes in Clinical Trial Participants vs Medicare Beneficiaries

Author Affiliations
  • 1Office of Pharmacovigilance and Epidemiology, Food and Drug Administration, Silver Spring, Maryland
  • 2Acumen LLC, Burlingame, California
  • 3Office of Hematology and Oncology Products, Division of Hematology Products, Food and Drug Administration, Silver Spring, Maryland
  • 4Division of Biometrics, Office of Biostatistics, Food and Drug Administration, Silver Spring, Maryland
  • 5Department of Economics, Stanford University, Stanford, California
  • 6Centers for Medicare & Medicaid Services, Woodlawn, Maryland
JAMA Oncol. 2020;6(2):248-254. doi:10.1001/jamaoncol.2019.3994
Key Points

Question  How do outcomes in idelalisib (IDEL) treatment of relapsed follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) in the clinical setting compare with the treatment outcomes in clinical trials?

Findings  In this cohort study of 115 clinical trial participants and 599 Medicare beneficiaries aged 65 years or older treated with IDEL, Medicare beneficiaries were older, sicker, and had unfavorable imbalances in treatment duration, mortality, and fatal infections compared with clinical trial participants.

Meaning  Patients treated with IDEL in the clinical setting had less favorable treatment outcomes than those in clinical trials.


Importance  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.

Objective  We compared IDEL treatment outcomes in the clinical setting with outcomes in clinical trial data.

Design, Setting, and Participants  This cohort study compared clinical trial participants treated with IDEL, aged 65 years or older, in studies 101-09 and 312-0116 with Medicare beneficiaries treated with IDEL of the same disease state and treatment regimen. Study 101-09 was a phase 2, single-group, open-label trial supporting accelerated approval of IDEL for relapsed or refractory FL. Study 312-0116 was a phase 3, multicenter, randomized, double-blind trial supporting approval of IDEL+R for relapsed CLL. Analyses were conducted between February and December 2018.

Main Outcomes and Measures  Treatment duration, on-treatment and overall mortality, and serious and fatal infections were compared between trial participants and Medicare beneficiaries. Cox proportional hazards models quantified differences by cohort.

Results  We identified 26 trial participants (mean [SD] age, 73 [4.9] years; 12 [46.2%] women) and 305 Medicare beneficiaries (mean [SD] age, 76 [6.9] years; 103 [54.8%] women) receiving IDEL for FL and 89 trial participants (mean [SD] age, 74 [6.0] years; 30 [33.7%] women) and 294 Medicare beneficiaries (mean age, 76 [6.3] years; 111 [37.8%] women) receiving IDEL+R for CLL. Medicare beneficiaries were older with higher comorbidity; had a shorter median treatment duration for CLL (173 days vs 473 days, P < .001) but not FL (114, days vs 160 days, P = .38); a numerically higher mortality rate (CLL: HR, 1.40; 95% CI, 0.93-2.11; FL: HR, 1.39; 95% CI, 0.69-2.78); and a significantly higher fatal infection rate per 100 person-years for CLL (18.4 vs 9.8, P = .04) and a numerically higher rate for FL (27.6 vs 18.6, P = .54), compared with trial participants. Trial participants had approximately twice as many dose reductions (CLL: 32.6% vs 18.0%; P = .003; FL: 38.5% vs 16.1%; P = .02). Among Medicare beneficiaries, a hospitalized infection within 6 months prior to IDEL initiation was associated with a 2.11-fold increased risk for on-treatment fatal infections (95% CI, 1.44-3.10). Despite a March 2016 recommendation for Pneumocystis jirovecii pneumonia prophylaxis in patients treated with IDEL, prophylaxis rates were low after March 2016 (FL: 25%, CLL: 37%).

Conclusions and Relevance  We observed substantial imbalances in baseline comorbidities and treatment outcomes between Medicare beneficiaries and trial participants aged 65 years or older. 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.

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