Efficacy and Safety of Ino Combined with Reduce Dose R-GDP Regimen in Patients with Relapsed/Refractory B-Cell NHL in China

Abstract

Background: The combination of immunochemotherapy resulted in satisfactory efficacy and survival for B-cell Non-Hodgkin Lymphoma (NHL). But many patients face no response to combination therapy or the disease progression again. This study aimed to investigate the efficacy and safety of Inotuzumab Ozogamicin (InO) combined with reduce dose R-GDP as a salvage therapy in patients with relapsed/refractory (R/R) B-NLH. Patients and methods: Seven patients with R/R B-NLH or even failure of anti-CD19 and CD22 chimeric antigen receptor (CAR) T cell therapy received InO combined with reduce dose R-GDP combination therapy. All patients received Rituximab (R) 375mg/m 2 intravenously (IV) on day -1, and InO 0.8 mg/m 2 (IV) on day 0. Then Gemcitabine (G) 500-1000mg/m 2(IV), Dexamethasone (D) 40 mg/day (IV) on day 1-4 and Cisplatin (P) 40-75mg/m 2 (IV) on day 1 of each 21-day cycle (±2 days). Treatment was continued for up to two cycles unless progressive disease (PD) or intolerable toxicity occurred. The primary endpoint of this study was the Complete remission (CR) and Overall response rate (ORR). The secondary endpoint of this study was Progression-free survival (PFS), Overall survival (OS) and Adverse events (AE), particularly hematological toxicity. In our study, the response evaluation was detected using computed tomography (CT) or PET-CT. Results: Seven patients with R/R B-NLH received 1-2 cycles of InO combined with reduce dose R-GDP therapy. Three patients did not respond to anti-CD19 and CD22 CAR-T cell therapy or their disease progressed again. The other four patients did not respond to more than 3 lines of combined immunochemotherapy and never achieved Partial response (PR) or CR. Four patients with R/R B-NLH who received 1-2cycles of InO combined with reduce dose R-GDP therapy achieved CR and survived to this day. Three of the four patients had previously received anti-CD19 and CD22 CAR-T cell therapy. Two patients with R/R B-NLH achieved PR after one cycle of InO combined with reduce dose R-GDP therapy, the other one patient achieved Stable disease (SD) only. One R/R B-NLH patient who achieved CR after one cycle of this salvage therapy had a PFS of one year to date without any other treatments. The other three R/R B-NLH patients who achieved CR after 1-2 cycles of this salvage therapy had a PFS of 3-6 months without any other treatments. The other two patients who achieved PR after 1 cycle of this salvage therapy survived 7 months and 2 months, while the only one patient who achieved SD survived one month without any other treatment. The main AE of this study was hematological toxicity. Three patients were defined as 3-4 grade of neutropenia, four patients were defined as 3-4 grade of anemia and three patients were defined as 3-4 grade of thrombocytopenia in this study. Except for one patient who was defined as grade 3 of thrombocytopenia recovered nine months after this salvage therapy, all other patients recovered two to three months after this study. There have been no deaths from severe infections due to hematological toxicity. Conclusions Ino combined with reduce dose R-GDP therapy in patients with R/R B-NLH could be an effective and safety therapy. However, the GDP regimen needs to be reduced appropriately to avoid severe hematological toxicity.