NCRI PETREA TRIAL: A PHASE 3 EVALUATION OF PET‐GUIDED, RESPONSE‐ADAPTED THERAPY IN PATIENTS WITH PREVIOUSLY UNTREATED, ADVANCED‐STAGE, HIGH‐TUMOUR‐BURDEN FOLLICULAR LYMPHOMA

Abstract

Introduction: Frontline treatment for advanced stage, high tumour burden follicular lymphoma (FL) usually consists of 6-8 cycles of chemotherapy combined with the CD20 antibody rituximab (R) or GA101/obinutuzumab (G). The PRIMA trial showed that R maintenance following R+chemo induction improves PFS but also increases toxicity with no OS advantage. The separation of PFS curves suggests that its main effect is to delay relapse in the minority of patients destined to progress within the first 2-3 years. The GALLIUM trial showed that replacing R with G further improves PFS but also increases toxicity and likewise has no OS advantage. FDG PET-CT (PET) imaging has emerged as a powerful predictor of both PFS and OS following frontline R/G+chemo induction in FL. Most patients who achieve a complete metabolic response (CMR, Deauville 1-3) experience prolonged remissions irrespective of anti-CD20 maintenance whereas those who remain PET +ve (Deauville 4-5) have an increased probability of early disease progression. We therefore hypothesised that the PFS benefit of maintenance is largely confined to anatomical responders who remain PET +ve and is of limited magnitude in those who achieve a CMR. The PETReA trial was developed to test this hypothesis and also to investigate treatment intensification in the PET +ve population by adding lenalidomide to anti-CD20 maintenance. The combination of lenalidomide plus R is highly effective in FL, being superior to R in the relapsed/refractory setting and non-inferior to R+chemo in the frontline setting. Encouraging phase II data have also been obtained with lenalidomide plus G. Methods: PETReA is a non-blinded, phase 3 randomised controlled trial for patients with previously untreated (excepting local radiotherapy), advanced-stage FL (grade 1, 2, 3a) meeting the GELF criteria for starting treatment. Patients receive R+chemo with the option of CVP, CHOP or bendamustine. Anatomical responders are grouped based on post-induction PET status: those who achieve a CMR (Deauville 1-3) are randomised 1:1 to R maintenance (8 weekly for 12 doses) versus no further treatment, whereas those who remain PET +ve (Deauville 4-5) are randomised 1:1 to R maintenance with or without lenalidomide. The primary endpoint is PFS with secondary endpoints including OS, toxicity, quality of life, conversion to PET negativity (PET +ve group only) and response to induction therapy. The study opened in the UK in May 2018 and Australia in February 2019 and is recruiting at the expected rate. Keywords: follicular lymphoma (FL); positron emission tomography (PET). Disclosures: Pettitt, A: Research Funding: Celgene, Chugai, Gilead, GSK/Novartis, Roche, Verastem; Other Remuneration: Celgene, Gilead. Barrington, S: Consultant Advisory Role: Hofman la Roche; Honoraria: Hofman la Roche; Research Funding: Bristol Myers Squibb, Amgen, Celgene, Hofman la Roche. Kalakonda, N: Research Funding: Celgene. Khan, U: Research Funding: UK is an MRC Clinical Training Fellow based at the University of Liverpool supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (Award Ref. MR/N025989/1), Roche Pharma, Eli Lilly and Company Limited, UCB Pharma, Novartis, the University of Liverpool and the University of Manchester. Ardeshna, K: Other Remuneration: Advisory boards and assistance to attend conferences (travel registration and accommodation) from Roche, Takeda, Celgene, ADC Therapeutics. Eyre, T: Honoraria: Roche, Gilead, Janssen, Abbvie; Other Remuneration: Research support; Travel to scientific conferences from Gilead; travel to scientific conference from Abbvie. Fox, C: Consultant Advisory Role: Abbvie, Adienne, Celgene, Gilead, Janssen, Roche, Takeda, Sunesis, Atarabio; Honoraria: Abbvie, Adienne, Celgene, Gilead, Janssen, Roche, Takeda, Sunesis, Atarabio; Research Funding: Abbvie, Adienne, Gilead, Roche. Linton, K: Consultant Advisory Role: Celgene; Roche; Janssen; Takeda; Honoraria: Janssen; Hartley-Taylor; Roche; Other Remuneration: Janssen; Celgene; Takeda (sponsorship to attend conferences). Malladi, R: Honoraria: Roche; Research Funding: Celgene; Other Remuneration: Travel Support/Meeting attendance from Celgene. Menne, T: Honoraria: Pfizer, Amgen, Novartis, Roche, Daiichi, Kite, Celgene, Takeda; Research Funding: Janssen, Astra Zeneca. Okosun, J: Honoraria: Gilead; Research Funding: Gilead, Epizyme. Rule, S: Consultant Advisory Role: Celgene, Roche, Astra Zeneca, Janssen, Sunesis; Honoraria: Celgene, Roche, Astra Zeneca, Janssen, Sunesis; Research Funding: Janssen. Johnston, A: Consultant Advisory Role: Yes; Other Remuneration: Support to attend meeting. Trotman, J: Research Funding: Janssen, PCYC, Roche, Celgene, Beigene.