ESTRO 2023 - Abstract Book

S338

Sunday 14 May 2023

ESTRO 2023

Patients with stage I-II FL, grade 1-3a, staged with CT and bone marrow biopsies +/- FDG-PET were randomized to either; Arm A: 30Gy IFRT alone or Arm B: IFRT followed by 6 cycles of cyclophosphamide 1000 mg/m2 IV D1, vincristine 1.4 mg/m2 D1 and prednisolone 50mg/m2 D1-5 (CVP). From 2006 Rituximab 375 mg/m2 D1 was added to arm B (R-CVP). PET staging gradually became widely adopted. Stored trial biospecimens were analysed for potential prognostic factors, including plasma beta 2 microglobulin (B2M) and gene expression in FFPE tumour biopsies, assessed by nanostring analysis. Results From February 2000 to July 2012, 150 patients were, recruited: 75 to arm A (IFRT) and 75 to arm B (44 CVP and 31 R-CVP). Median age was 57, 75% had stage 1 and 48% were PET-staged. At the trial close out date, (median potential follow-up 11.3 years), PFS remained significantly superior for arm B (IFRT + systemic therapy) compared to arm A (HR 0.6 (0.37-0.98); p=0.043). 10 years PFS was 62% for arm B and 43% for arm A. 10 year OS was 95.3 and 84% respectively for arms A and B (HR 0.44, p=0.10). Patients treated with R-CVP had substantially superior PFS compared to those who received IFRT or CVP (81% vs 52% at 8 years, P=0.013, figure 1). When analysis of PFS was confined to 72 PET-staged patients the difference between arms A and B increased (HR 0.35 p=0.027, Figure 2), whereas analysis confined to 78 non-PET staged patients showed no significant difference between arms (HR 0.8, p=0.42). More than twice as many deaths (13 vs 6) and transformations to aggressive lymphoma (11 vs 5) occurred in Arm A than Arm B. By last follow-up 16 patients had experienced transformation with 11 and 5 cases detected in arms A and B respectively. The HR for either histological transformation or death was 4.0 (p=0.045), consistent with a favourable change in natural history with systemic therapy. Emphasizing the importance of the cytotoxic CD8+ T-cell response, both elevated plasma B2M (HR 2.27, p=0.044) and low intratumoural CD8A gene expression (HR 2.21, p=0.0042) were associated with inferior PFS. Conclusion Systemic therapy, especially with rituximab, increased progression free survival and significantly reduced the risk of death or transformation to aggressive lymphoma in stage I-II FL. Most benefit was seen in PET staged patients. Elevated B2M and lower gene expression associated with anti-tumour immunity were associated with worse outcomes.

OC-0438 Patterns of failure in 559 primary central nervous system lymphoma patients treated from 1983-2020