End-of-Treatment 18[F]-FDG PET Can Predict Progression-Free Survival in Patients Undergoing Bendamustine + Rituximab for First Relapsed/Recurrent Follicular Lymphoma: The Result of W- J H S NHL01 Study

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.5245-5245
• Main Authors: Rai, Shinya, Kato, Koji, Suzumiya, Junji, Izutsu, Koji, Nishikori, Momoko, Shibayama, Hirohiko, Maeda, Yoshinobu, Yoshimura, Kenichi, Tateishi, Ukihide, Miyamoto, Toshihiro, Ishikawa, Jun, Takahashi, Tsutomu, Yamauchi, Takahiro, Akashi, Koichi, Kanakura, Yuzuru
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-126455

Background: Follicular lymphoma (FL) is the most common indolent B-cell lymphoma, and its clinical behavior is heterogeneous. FL is sensitive to immunochemotherapy with anti-CD20 antibody, but characterized by a high rate of relapse and having a risk of histological transformation. Bendamustine + rituximab (BR) therapy is one of standard treatment options for both untreated and relapsed FL. There are several reports that 18[F]-Fluoro-2-deoxy-D-glucose(¹⁸F-FDG) PET-CT (PET) response after induction therapy can predict progression-free survival (PFS) in FL undergoing first-line immunochemotherapy. However, the significance of PET after second-line therapy has rarely been evaluated, especially in a prospective setting. Thus, we conducted a single arm prospective phase 2 study to compare 1-year (1-yr) PFS between patients with PET-positive and PET-negative at end-of-treatment (EOT) response assessment using standardized PET and CT after the BR therapy in patients with first relapsed or recurrent FL (UMIN000013756). Method: The W-JHS NHL01 study is a prospective multicenter phase 2 trial, which included adult (≥20 years) patients with relapsed or recurrent FL (CD20 positive, grade 1-3a), ECOG-PS (≤2) and measurable lesion (CT minor axis >1.0cm). Patients had to have one prior regimen with chemotherapy and/or rituximab. Histologic transformation at recurrence was ineligible. Patients were treated with 6 cycles of BR (R 375 mg/m2 d1, B 90 mg/m2 d1-2, every 28 days). EOT PET within 1-2 months after last BR was evaluated, and assessments for progression were made using contrast enhanced CT scans at 12 and 18 months after the registration of this study and at physician's discretion thereafter. Standardized PET and contrast enhanced CT were evaluated centrally by independent expert radiologists and the PET positivity was defined by a residual ¹⁸F-FDG uptake score of 4 or greater (5-point scale). The efficacy of treatment was evaluated by CT scan according to Cheson 2007 criteria. The primary endpoint was 1-yr PFS. Key secondary endpoints were overall response rate (ORR), CR rate (CRR), 1-yr overall survival (OS). Results: Between July 4, 2014 and Jan 24, 2017, 75 patients were enrolled, eight of whom were excluded from the analysis. Because 4 received fewer than 4 cycles of BR, 2 received with non-standardized PET and 2 had progression disease. Of the remaining 67 patients in the efficacy-evaluable population, median (range) age was 63 (47-83) and 27/67 (40%) were ma