P1091: clinical implications of t cell subset composition during maintenance therapy after first-line immunochemotherapy containing bendamustine in patients with follicular lymphoma

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: First-line immunochemotherapy of Follicular lymphoma (FL) combining anti-CD20 antibodies Rituximab or Obinutuzumab with Bendamustine (R/O-B) followed by maintenance therapy results in high rates of response and long progression-free survival. A major adverse effect of this regimen is long-lasting lymphopenia as a risk factor for infections. Aims: We performed a cross-sectional and longitudinal study on lymphocyte T cell subsets during anti-CD20 maintenance therapy using flow-cytometry. Associations between T cell subset counts and infectious events were analyzed. Methods: We enrolled 55 patients (pts) with high tumor burden FL between 2017 and 2021 who received first-line treatment with anti-CD20 plus Bendamustine (R/O-B) or CHOP regimen (R-CHOP), followed by maintenance. We collected peripheral blood samples at the following time points: end of induction (EoI), at +6, +12, +18 and +24 months after. We analyzed T cell subsets defined by the maturation status (Naïve, Central Memory, Effector Memory, and TEMRA) in addition to absolute CD4+ and CD8+ T cell counts. Results: We enrolled 55 pts: 49% females, 51% males, median age 60 years (range 50- 80), who received R/O-B (76%) and R-CHOP (24%). At the EoI median CD4+ counts were lower in the R/O-B group compared to R-CHOP (119/mmc vs 402/mmc; p =0.0001). Despite the trend of CD4+ counts to increase over time following R/O-B, they remained significantly lower at +6 (155/mmc vs 637/mmc p=0.0008) and +12 (264.6/mmc vs 497.3/mmc; p=0.027), when compared to R-CHOP. Most strikingly, the median CD4+ naive count was extremely low in R/O-B group at EoI (3.43/mmc vs 71.3/mmc; p=0.003) and up to +12 (26/mmc vs 173/mmc; p=0.04), while no differences were observed at +18 and +24. We didn’t find differences in T CD8+ counts and subsets between R/O-B and R-CHOP group at any time. Gender and age had a significant impact on T cell recovery in R/O-B treated pts. Males (M) had prolonged lower CD4+ counts respect to females (F) (146/mmc vs 316/mmc at +12 for M vs F, p=0.018; 230/mmc vs 425/mmc at +24 for M vs F, p=0.026). Moreover, the proportion of naïve CD4+ T cells remained lower in M than in F (from 9% vs 15% at +6, p=0.05, to 11% vs 35.4% at +24, p=0.045). As age increases lower naïve CD4+ count is observed at +6 (p=0.0019) and +12 months (p=0.016). Infectious episodes were registered during the 2 year-observation period in 47% of pts. 60% of infections were bacterial, 30% reactivation of VZV, and 10% fungal. The cumulative incidence rate of infection was significantly different between R/O-B and R-CHOP (59% vs 7 % p= 0.003). In univariate analysis age>60 years and more than 12 months to reach CD4+>200/mmc were identified as risk factors for infections in the R/O-B group (respectively OR 4.87, CI 1.23 -19, p =0.024; OR 7, CI 95% 1.59-30, p =0.014). These variables were confirmed in multivariate analysis (respectively OR 4.34, CI 95% 1.012-18.6, p=0.048; OR 1.13, CI 95% 1-1.28, p=0.05). Summary/Conclusion: FL pts undergoing first-line therapy with R/O-B experienced a prolonged and deep CD4+T and lymphopenia, in particular of the naïve CD4+ T cell subset compared with pts treated with R-CHOP. Elderly Male pts showed a particularly delayed recovery of CD4+ T cell counts. Prolonged CD4+ T cell lymphopenia over 12 months and age>60 ys are risk factors for infections, and could be indicators for the necessity to prolong anti-microbial prophylaxis. Moreover, benefits of the R/O-B regimen should be weighed against the risks of infections in particular among elderlies. Keywords: Follicular lymphoma