Early fdg‐pet adapted treatment of limited stage hodgkin lymphoma (hl): 10y long term follow‐up analysis of the randomized intergroup eortc/lysa/fil h10 trial

Background: Though the outcome of patients with stage I/II HL is excellent with standard combined chemo- and radiotherapy, the H10 trial assessed the possibility of improving tumor control by treatment intensification in early (i.e., after two cycles of ABVD) PET-positive patients and of reducing treatment related toxicity by omission of involved-node radiotherapy (INRT) in early PET-negative patients. Here, we present the results of 10y long term follow-up analysis, focused on progression-free survival (PFS), and overall survival (OS). Methods: H10 was a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of ABVD in previously untreated stage I and II HL—according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U). The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of BEACOPPesc and INRT (superiority design). Primary end point was progression-free survival (PFS). In January 2019, a preplanned analysis on 10y follow-up was launched. So far, out of 1925 patients constituting the original study population, 1419 cases have been updated, and are included in the present analysis; 506 cases showing similar baseline characteristics and 5y OS and PFS than updated patients were excluded so far. Results: After a median follow-up of 9.5 yrs, a total of 57 deaths and 136 events for PFS were reported in the analyzed population, leading to an overall 10-year OS and PFS rates of 96% and 90% respectively. In ePET-positive patients, 10y PFS increased from 79% for standard ABVD + INRT to 85% for intensification to BEACOPPesc + INRT (hazard ratio [HR] = 0.67; 95% CI, 0.37 to 1.20), although the difference was not statistically significant. The 10y OS rates were 90% and 92%, respectively (hazard ratio [HR] = 0.92; 95% CI, 0.43–1.97). In the F ePET negative group the 10y PFS rates were 99% versus 85% (HR = 13.2; 95% CI, 3.1–55.8) in favor of ABVD + INRT, and the difference was statistically significant. The 10y OS rates were 100% versus 98% for ABVD + INRT and ABVD only arms, respectively (hazard ratio [HR] = 2.80; 95% CI, 0.3–26.9). Finally, in the U ePET negative group 10y PFS rates were 91% and 87% (HR = 1.52; 95% CI, 0.8–2.8) for standard and experimental arm, respectively. The 10y OS rates were 94% versus 95% for ABVD + INRT and ABVD only arms, respectively (hazard ratio [HR] = 0.84; 95% CI, 0.4–2.0). Conclusion: The present long-term analysis confirms that in F ePET-negative patients, the omission of INRT is associated with lower 10y PFS, although no differences in terms of OS emerged. Moreover, in the U ePET negative and in the ePET positive patients, no significant differences between standard and experimental arms emerged in terms of 10y PFS and OS. Keyword: Hodgkin lymphoma No conflicts of interests pertinent to the abstract.