Rituximab Overcomes Sex as a Strong Adverse Prognostic Factor for Treatment Outcome in Patients with Follicular Lymphoma: Analysis of Patients Treated with Rituximab/CHOP or CHOP in Randomized Trials of the German Low Grade Lymphoma Study Group (GLSG).
Authors: Buske Christian , Hoster Eva , Dreyling Martin H. , Forstpointner Roswitha , Kneba Michael , Schmitz Norbert , Schmits Rudolf , Metzner Bernd , Hallek Michael , Lengfelder Eva , Hiddemann Wolfgang , Unterhalt Michael 
Published: October 2019

Abstract
Abstract 3706
Poster Board III-642
Sex has been recognized as an important prognostic factor for the treatment outcome of patients with lymphoma. Thus, several retrospective analyses have shown that male sex is associated with an inferior outcome in advanced stage follicular lymphoma. This was confirmed in a retrospective analyses of 1795 patients with follicular lymphoma using Cox regression analysis, in which male sex was independently associated with inferior survival (Solal-Celigny et al., Blood 2004). We now analyzed the prognostic impact of sex on treatment outcome of 1172 patients with follicular lymphoma treated first line with CHOP or R-CHOP in prospectively randomized clinical trials of the German Low-Grade Lymphoma Study Group (GLSG). From these, 616 pts were treated with CHOP, 556 pts with R-CHOP. FLIPI was equally distributed between the two treatment arms (low risk 14% vs. 14%, intermediate risk 42% vs. 41% and high risk 44% vs. 45 %, respectively). 48% of the patients were male (50% in the CHOP and 46% in the R-CHOP arm). For all patients there was a significantly inferior time to treatment failure (TTF) for male patients with a median of 43 months compared to 61 months for female patients (p=0.0035). In the patient group treated with CHOP alone the median TTF was 30 months for male vs. 40 months for female patients (p=0.0041). The observation that male sex was associated with inferior treatment outcome was seen both in the elderly (above 60 yrs of age) as well as the younger patient group (below 60 yrs of age). However, after treatment with R-CHOP sex did not affect treatment outcome anymore with virtually the same results in male vs. female patients (for the total group and for patients < 60yrs TTF median not reached in both arms, p = n.s.; for pts > 60 yrs TTF 81 vs. 84 months, respectively, p=n.s.). In multivariate analysis, also adjusting for FLIPI risk factors, male sex showed up as an independent prognostic factor for patients treated with CHOP alone (HR 1.82; 1.32 – 2.5; p=0.0002), but not for patients treated with R-CHOP (HR 1.06; 0.68 - 1.66, p = 0.79; p=0.0476 for the interaction term of sex with Rituximab). Based on this, male patients had the highest benefit when rituximab was added to CHOP (R-CHOP vs. CHOP: male pts HR 0.31,0.21 - 0.46, p<0.0001 and female pts. HR 0.53, 0.37 - 0.76, p = 0.0005). These data demonstrate that Rituximab functions as an equalizer with regard to sex as a prognostic factor and underlines that well established prognostic factors may lose their predictive power with the emergence of novel effective treatment approaches.

Disclosures:
Buske: Roche: Honoraria. Hoster:Roche: travel support. Dreyling:Roche: Honoraria, Research Funding. Hallek:BayerScheringAG: Honoraria, Research Funding. Hiddemann:Roche: Honoraria, Research Funding. Unterhalt:Roche: .