RESPONSE‐ADJUSTED THERAPY FOR ADVANCED HODGKIN LYMPHOMA (RATHL) TRIAL: LONGER FOLLOW UP CONFIRMS EFFICACY OF DE‐ESCALATION AFTER a NEGATIVE INTERIM PET SCAN (CRUK/07/033).

Abstract

Introduction: This prospective randomized trial tested whether FDG PET-CT after 2 months of chemotherapy could be used to guide subsequent treatment for patients with advanced classical Hodgkin lymphoma (HL). Methods: Adult patients (pts) with newly diagnosed HL (Ann Arbor stages IIB-IV, or IIA with bulk or ≥3 involved sites) underwent paired baseline and interim PET-CT scans after 2 cycles of ABVD (PET2). Images were reviewed centrally using the 5-point scale as negative (1-3) or positive (4-5). Pts with negative scans were randomised to ABVD or AVD for 4 more cycles. Pts with positive scans proceeded to intensification with either BEACOPP-14 or escalated BEACOPP. Radiotherapy (RT) was permitted, but not advised for pts with interim negative scans, irrespective of baseline bulk or residual masses. Results: 1202 eligible pts received treatment. Following a negative PET2, 952 pts were randomised to continue ABVD or AVD. With a median follow-up of 52 months, PFS at 3 years for ABVD was 85.4% (95% CI: 81.9 - 88.4), and for AVD 84.0% (80.3-87.1). The 1.2% difference in 3 yr PFS (95% CI -3.7 - 4.8) now lies within the predefined noninferiority margin of 5%. There was a similar 5 yr PFS of 82.7% (78.8 -86.0) and 80.6% (76.2 - 84.2) and OS of 95.3% (93.7 - 97.0) and 95.0% (92.1 - 96.8) for ABVD and AVD respectively. Among 172 pts with a positive PET2, 5 year PFS was 65.7% (57.9 - 72.5) and 5 year OS 85.1% (78.3-89.9%). 197 pts with bulky stage II HL were analysed separately. Eleven patients were not evaluable due to: declined randomisation n = 2, death n = 1, larceny n = 1 and PET scan error n = 7. PET2 was negative in 147 (75%): 69 were randomized to ABVD and 7 also received consolidation radiotherapy (RT); 78 received AVD of whom 11 had RT. 3 year PFS was 89% (82.5 - 93.0) with no (Figure Presented) significant difference between ABVD and AVD, RT or no RT, presence or absence of a residual mass, or PET score (1-3). The remaining 39 pts with bulky stage II HL and a positive PET2 received BEACOPP. of the 11 patients receiving RT, there was just 1 progression, despite only 5 reaching conventional CT based CR or CR(u). Conclusion: With longer follow-up, these RATHL results confirm that the primary study endpoint has been met, reliably excluding a 5% inferior 3 year PFS following de-escalation after a negative interim PET-CT. The omission of bleomycin does not significantly affect PFS or OS in pts with negative PET2. With the caveat that this is a non-randomised subgroup, it appears that in pts with bulky stage II HL, those who achieve a negative PET2 have excellent outcomes without the use of radiotherapy. For those with a positive PET2, escalated therapy with BEACOPP and consolidation RT is effective treatment. Figure: PFS in randomised PET2 negative patients. Difference at 3 years calculated by applying the hazard ratio (1.08, 95%CI: 0.79 -1.48) to the 3 year estimate in the AVD arm.