ALBERT

Description: Background Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor 2 (VEGFR-2) to inhibit tumor angiogenesis, and has shown encouraging anti-tumor effects in multiple solid tumors. Yet clinical evidence of apatinib as a potential treatment choice for RR DLBCL remains rare. In current study, we evaluated the efficacy and safety of Apatinib for patients with RR DLBCL. Methods In this open-label, single-arm, prospective study, we enrolled patients aged 14-70 years with treatment failure of at least two chemotherapeutic regimens using Simon's two stage design. All patients took Apatinib at an initial dose of 500mg on a 4 weeks cycle at home and visited outpatient clinic every 2 cycles to evaluate the efficacy and to record the adverse events. Dose interruptions and reductions were only allowed when there were grade 3 haematological adverse events or grade 2 non-haematological adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.) Results From January 2017 to February 2019, we screened 35 and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate (DCR) of 71.9%. The median PFS was 6.9 months (95%CI 5.8-7.9) and the median OS was 7.9 months (95%CI 7.0-8.7). Kaplan-Meier estimates of PFS and OS are shown in Figure 1. For patients achieved PR, The median DoR was 5.0 months (95%CI 3.5-6.5). At data analysis time, the median duration of follow-up was 8.6 months (95%CI 7.3-9.4), and 16 (50.0%) patients remained on treatment. 21 patients showed tumor shrinkage comparing with their baseline data and the best percentage changes from baseline are shown in Figure 2. The most common grade 3-4 adverse events (AE) were hypertension (12.6%), hand-foot syndrome (9.4%) and leukopenia (6.3%). No Apatinib-related deaths were noted. AEs arose in at least one patient are shown in Table 1. Conclusion With the potential superiority of home administration without frequent hospitalization, apatinib can be an arrow in the bow for RR DLBCL patients considering its favorable efficacy, manageable AEs, improved patient adherence and economic effectiveness. Further investigations into this topic will be of profound significance. Disclosures No relevant conflicts of interest to declare.

Description: Background Extranodal NK/T cell lymphoma (ENKTL) is rare in western countries but rather common in Asia and South America, characterized with Epstein-Barr virus (EBV) infection. Patients with advanced stage (III/IV) ENKTL has a poor survival and low response to conventional CHOP-like chemotherapy, with a 5-year overall survival rate of only 30%. Retrospective study showed that SMILE regimen had a certain effect on ENKTL, but the toxicity limited its further clinical application. More effective treatment regimens are required to be explored for systematic, prospective, controlled, randomized clinical trials. Recently, studies revealed that asparaginase-based combination chemotherapy such as P-Gmox(Pegaspargase, Gemcitabine, Oxaliplatin)is effective in patients of ENKTL. However standard treatment for newly untreated advanced ENKTL is still controversial. We developed a refined chemotherapeutic DDGP (dexamethasone, cisplatin, gemcitabline, and peg-asparaginase) regimen and proceeded a prospective randomized, multicenter and open-label clinical trial to evaluate and compare the efficacy and safety of DDGP with SMILE regimen in patients with newly diagnosed stage III/IV ENKTL in January 2011. Based on the encouraging interim results in 2016(Li, L et al.Clin Cancer Res, 2016), we presented the final results of this clinical investigation (ClinicalTrials.gov, No. NCT01501149). Patients and methods: The study was initiated at 9 centers in China in January 2011. Patients aged 14-70 with newly diagnosed ENKTL in stages III/IV, and ECOG performance score of 0-2 were enrolled. According to a computer-generated randomization schedule, eligible patients were assigned either DDGP regimen (cisplatin 20 mg/m² on day 1-4; dexamethasone 15mg/m2 on d1-5; gemcitabine 800mg/m2 on d1,8; pegaspargase 2500 IU/m2 on d1; 21 days per cycle)or SMILE regimen (methotrexate 2g/m2 on d1; dexamethasone 40mg/m2 on d2-4; ifosfamide 1500mg/m2 on d2-4; L-asparaginase 6000 U/m2 on d3-9; etoposide 100 mg/m2 on d2-4; 21 days per cycle) for up to 6 cycles unless disease progression, unacceptable toxicity or patient rejection. Efficacy was evaluated every two cycles. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall response rate (ORR) and overall survival (OS). In addition we compared the safety and tolerability between DDGP and SMILE regimens. The Kaplan-Merier method was used to evaluate for survival of freedom from events, and the log-rank test was used to evaluate differences among two groups. Results: A total of 87 eligible newly diagnosed advanced ENKTL patients were randomly assigned for the study and 80 patients were included into intention-to-treat population (40 patients in DDGP group and 40 patients in SMILE group). Data were collected from January 2011 to February 2019. Baseline characteristics of the two group patients were well balanced. At median follow-up of 41.5 months, the median PFS and OS in the SMILE group were 6.83 months and 75.2 months, respectively, while the median PFS and OS in the DDGP group have not been reached (Fig 1). The 3-year PFS rate and 5-year OS rate in DDGP group were higher than in SMILE group (56.6% vs. 41.8% for 3-year PFS, P=0.004; 74.3% vs. 51.7% for 5-year OS, P=0.02). No difference of the complete remission (CR) rate was observed between two groups, while overall response rate (ORR) in DDGP group was higher than in SMILE group (90.0% vs. 60.0%, p=0.002) (Table 1). More frequently 3/4 grade hematologic toxicities such as leucopenia and netropenia were observed in SMILE group than in DDGP group (p=0.022, p=0.015). Non-hematologic toxicities included elevated transaminase, mucositis and allergy were higher in SMILE group than in DDGP group(p=0.027, p

Description: Objective:To evaluate the safety, efficacy, and feasibility of rituximab, fotemustine, pemetrexed and dexamethasone (R-FPD) regimen for primary central nervous system lymphoma (PCNSL) patients. Methods:A prospective, single-center, single-arm, phase II clinical trial. Patients with newly diagnosed PCNSL diagnosed from the First Affiliated Hospital of Zhengzhou University from July 2018 to July 2020. R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100mg/m2 i.v. on D1) ,pemetrexed (600mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1).(NCT04083066) Results: 30 patients were included. After two cycles, the objective response rate(ORR) was 96.4%(27/28,26 PR,1 CR,0 SD,0 PD,2 Censored),the disease control rate(DCR) was 96.4%(27/28); After four cycles, the ORR was 71.4% (15/21, 5PR,10 CR,1SD,5PD,7NR,2 Censored),DCR was 76.2%(16/21). The median progression-free survival (PFS) was 20.3 months (95%CI:5.2--35.4),The median overall survival (OS) was 22.0 months (95%CI:16.1-27.9).The grade III-IV toxicities were mainly leukopenia(17.9%), thrombocypenia(25%) and anemia(10.7%). Conclusion: Fotemustine-based in combination with Rituximab chemotherapy can improve outcomes with the progress free survival and the overall survival benefits, as well as with better tolerability for newly diagnosed PCNSL patients. Keywords: rituximab; primary central nervous system lymphoma; pemetrexed; fotemustine; efficacy Disclosures No relevant conflicts of interest to declare.