Tobias Polak

Chapter 6 122 TA604 Idelalisib for treating refractory follicular lymphoma In 2019, NICE assessed cost-effectiveness of idelalisib, used as monotherapy for refractory follicular lymphoma, a malignancy of B-lymphocytes. Idelalisib is a kinase inhibitor, reducing the activity of phosphoinositide 3-kinase p110δ (PI3Kδ), which is an enzyme involved in growth, proliferation, differentiation and survival of blood cells. PI3Kδ is known to be overactive in B-cell malignancies, and is therefore used as therapeutic target in follicular lymphoma. Gilead was the submitting company, and Kleijnen Systematic Reviews produced the Evidence Review Group (ERG) report. The single-arm main trial (DELTA) was supplemented with data from the Compassionate Use Program: The company supplemented the DELTA study with another source of evidence for idelalisib: the Compassionate Use Programme (CUP). This provided retrospective observational data from patients with follicular lymphoma having compassionate treatment in the UK and Ireland. The company took a subset of 79 patients with relapsed or refractory follicular lymphoma that had been treated with idelalisib. In these patients, median progression-free survival was 7.1 months, and median overall survival was not reached. The Committee decided that neither data set was ‘adequate enough for using to determine how well patients on idelalisib fared compared with people who had not taken idelalisib.’ Despite the absence of controlled trials, the committee discussed the evidence presented to determine which set (trial or CUP) was most generalizable to the use of idelalisib clinical practice. Evidence was ambivalent: • The committee noted the difference in Eastern Cooperative Oncology Group (ECOG) performance status and Follicular Lymphoma International Prognostic Index (FLIPI) I and II scores between DELTA and the CUP. Notably, 8% of patients in DELTA had an ECOG score of 2 to 4 compared with 25% of patients in the CUP, reflecting poorer performance among patients in the CUP. The clinical experts stated that the ECOG performance status in CUP more closely reflected clinical practice than that in DELTA. • The clinical experts noted that the time since completing the last therapy was shorter in DELTA than in the CUP, suggesting that patients in DELTA had a poorer prognosis Resulting in the ambivalent conclusion that ‘the populations in DELTA and the CUP were different. (…) Also, patient and disease characteristics at baseline differed, with some suggesting a more favourable prognosis in DELTA than in the CUP, and others suggesting the opposite.’ Even help from clinical experts could not resolve the issue, as ‘the clinical experts suggested that the CUP cohort was more likely to reflect the intended UK treatment population because it was a ‘real-world’ study with

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