BACKGROUND: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. PATIENTS AND METHODS: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. RESULTS: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. CONCLUSIONS: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. CLINICALTRIALS.GOV: NCT00790036.

4th Department of Internal Medicine Hematology University Hospital Hradec Králové; Faculty of Medicine Hradec Králové Czech Republic

Ankara University Medical Faculty Ankara Turkey

CHU de Quebec Hôpital de l'Enfant Jésus Quebec City Canada

Department of Clinical Hematology and Diagnostics Osaka University Graduate School of Medicine Osaka Japan

Department of Haematology CHU Haut Lévèque Bordeaux France

Department of Hematology and Oncology Nagoya Daini Red Cross Hospital Nagoya Japan

Department of Hematology National Cancer Centre Hospital Tokyo Japan

Department of Internal Medicine Hotel Dieu de France University Hospital Beirut Lebanon

Department of Internal Medicine University Hospital Brno Brno Czech Republic

Department of Medical Oncology National Cancer Centre Beijing; Cancer Hospital Chinese Academy of Medical Sciences Beijing; Peking Union Medical College Beijing China

Department of Medicine University of Alabama Birmingham USA; UAB CCC Bone Marrow Transplantation and Cell Therapy Program University of Alabama Birmingham USA

Division of Clinical Hemato Oncology Istituto Europeo di Oncologia Milan Italy

Division of Hematology and Stem Cell Transplantation Shizuoka Cancer Centre Shizuoka Japan

Hematology Department Azienda Ospedaliero Universitaria Careggi Florence Italy

Internal Medicine and Hematology Instituto Nacional de Cancerologia Bogota Colombia

Key Laboratory of Carcinogenesis and Translational Research Department of Lymphoma Peking University Cancer Hospital and Institute Beijing China

MayoClinic Rochester USA

Novartis Pharma Paris France

Oncology Clinical Development Novartis Pharmaceuticals Corporation East Hanover USA

Oncology Institute of Southern Switzerland Bellinzona Switzerland

Princess Margaret Cancer Centre Toronto Canada

Sungkyunkwan University School of Medicine Samsung Medical Centre Seoul South Korea

University of Texas Houston USA; MD Anderson Cancer Center Houston USA

References provided by Crossref.org

Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options

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ClinicalTrials.gov
NCT00790036