Efficacy, safety, and T-cell population dynamics of glofitamab monotherapy in relapsed/refractory B-cell lymphoma

Abstract

Abstract Purpose Patients with relapsed/refractory (R/R) B-cell lymphoma (BCL) have a poor prognosis. We evaluated the efficacy, adverse events (AEs) and changes of CD4+CD8+ T cell population in glofitamab monotherapy in patients with R/R BCL. Patients and methods All patients with R/R BCL received a single dose of obinutuzumab pretreatment (1,000 mg) 7 days before the first cycle of glofitamab. They received glofitamab at weekly doses of 2.5 mg, 10 mg, and 30mg, followed by glofitamab 30mg once every 3 weeks for a total of 6 cycles or died. The clinical response, complete response (CR) rate, overall response rate (ORR), level of interleukin-6 (IL-6), cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS), changes of CD4+CD8+ T cell population were observed in our study. Results In our study, eight patients with R/R BCL were included. All patients were accompanied by poor prognostic factors, among which four patients had received anti-CD19 chimeric antigen receptor (CAR) T cell therapy before (Table 1). Three patients (Pt 1,2,4) completed at least six cycles of glofitamab monotherapy. Two patients (Pt 3,6) completed four and two cycles of glofitamab monotherapy respectively due to the occurrence of infection during the treatment process. One patient (Pt 7) is undergoing continued treatment, while the other patient (Pt 8) has been bridged with CAR-T cell therapy. The last one patient (Pt 5) discontinued glofitamab monotherapy due to his disease progression. With the increase in the number of treatment cycles, the ORR and CR ratios rose from 6/8 and 0/8 for 2 cycles to 7/8 and 3/8 for 4 cycles (Figure 1A). The mean level of IL-6 in peripheral blood was 120.25±91.88 pg/mL in the first cycle, while it was 25.75±10.19 pg/mL in the second cycle. It returned to normal level in the third cycle (Figure 1B). Six patients (6/8) developed different grades of CRS, all of which were grade 1-2 CRS in the first cycle. But only one patient developed grade 1 CRS in the second cycle (Figure 1C). No patient developed ICANS of any grade. The main hematological toxicities are neutropenia (6/8) and thrombocytopenia (3/8) (Figure 1D). Two patients (Pt 3,6) had their treatment interrupted due to infection, and one of them (Pt 6) died of central infection. In all the three patients obtained CR (Pt 1,3,4), they had obvious T cell exhaustion after 1 to 3 cycles, especially the total CD3+ T cells and CD8+ T cells. Then the T cell counts returned to the normal level. Some patients obtained partial response (PR) (Pt 2,7) also have such characteristics of changes in T cell counts (Figure 2). ConclusionsR/R BCL patients with poor prognostic factors had a good response to glofitamab monotherapy. The ORR and CR ratios rose to 7/8 and 3/8 after 4 cycles of glofitamab therapy. After two cycles therapy, the incidence of CRS and the level of IL-6 decreased significantly. It is very interesting that T-cell exhaustion in the early stage of treatment might be associated with better therapeutic effects.