Dataset Information

Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma.

ABSTRACT: Idelalisib [Zydelig (Gilead Sciences, Inc.), also known as CAL-101 and GS-1101] was approved in 2014 in the United States and European Union for the treatment of three indolent B-cell neoplasms: relapsed/refractory chronic lymphocytic leukemia (CLL, in combination with rituximab), relapsed follicular lymphoma, and relapsed small lymphocytic lymphoma (as monotherapy). Furthermore, it was approved in the European Union as first-line therapy for poor-prognosis CLL with 17p deletions or TP53 mutations and in patients unsuitable for chemoimmunotherapy. Idelalisib is an orally bioavailable ATP-competitive kinase inhibitor that targets the PI3K p110 isoform ? (PI3K?) with high potency and selectivity. PI3K? is hyperactivated in B-cell malignancies and plays a pivotal role in the B-cell receptor pathway, a key oncogenic driver in B-cell malignancies. The near exclusive expression of the PI3K? isoform in hematopoietic cells and the selectivity of idelalisib for the PI3K? isoform are essential for its efficacy and tolerability, even in elderly patients unfit for chemotherapy. Idelalisib is the first PI3K inhibitor approved by the regulatory agencies; this approval will change the treatment landscape of indolent B-cell malignancies.

SUBMITTER: Yang Q

PROVIDER: S-EPMC4523214 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma.

Yang Qingshan Q Modi Prexy P Newcomb Terry T Quéva Christophe C Gandhi Varsha V

Clinical cancer research : an official journal of the American Association for Cancer Research 20150210 7

Idelalisib [Zydelig (Gilead Sciences, Inc.), also known as CAL-101 and GS-1101] was approved in 2014 in the United States and European Union for the treatment of three indolent B-cell neoplasms: relapsed/refractory chronic lymphocytic leukemia (CLL, in combination with rituximab), relapsed follicular lymphoma, and relapsed small lymphocytic lymphoma (as monotherapy). Furthermore, it was approved in the European Union as first-line therapy for poor-prognosis CLL with 17p deletions or TP53 mutatio ...[more]

PMID: 25670221

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Project description:ImportanceIdelalisib (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.ObjectiveWe compared IDEL treatment outcomes in the clinical setting with outcomes in clinical trial data.Design, setting, and participantsThis 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 measuresTreatment 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.ResultsWe 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 relevanceWe 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.

Dataset Information

Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma.

Publications

Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma.

Similar Datasets

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