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Phase 2 study finds that a new treatment combination may improve outcomes for people with relapsed or refractory Hodgkin lymphoma. A recent, phase 2 study in China has investigated a new treatment combination for classical Hodgkin lymphoma that has come back (relapsed) or not responded (refractory) after previous treatment. In this study, people with relapsed or refractory classical Hodgkin lymphoma who had had at least two previous treatments were given: camrelizumab on its own or cambrelizumab plus decitabine. Camrelizumab is a ‘checkpoint inhibitor’ that stops lymphoma cells hiding from your immune system. This allows your immune system to recognise and destroy the lymphoma cells. Some checkpoint inhibitors, such as nivolumab and pembrolizumab, are already available to treat certain people with relapsed or refractory Hodgkin lymphoma. Decitabine is a chemotherapy drug that works by turning on genes that stop cancer cells growing and dividing. Scientists think it might also boost your immune system’s response to treatment with checkpoint inhibitors. It is currently used to treat people with acute myeloid leukaemia who are not suitable for standard therapy. In this study, people who were treated with camrelizumab plus decitabine had a much higher response to treatment than people treated with camrelizumab on its own. The response also seemed to last longer in people who received camerlizumab plus decitabine, although longer-term results are needed to confirm this. These results show that drugs that alters gene activation in this way (called ‘epigenetic modulators’) have the potential to boost the anti-lymphoma response to checkpoint inhibitors. This is a promising new approach that could improve outcomes for people with relapsed or refractory Hodgkin lymphoma. The authors concluded that adding decitabine to camrelizumab was safe and had an ‘impressively high complete response rate’. Large-scale trials are planned to investigate the treatment further. To find out more about how clinical trials are used to study new treatments for lymphoma, or to search for a trial that might be suitable for you, visit LIPA clinical trials link.   Source: lymphoma-action.org.uk  

On Wednesday 27 March 2019, Oral Session 20 (OS20) took place at the 45th Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT), Frankfurt, DE. During that session, Abstract OS20-2 was presented by Yongxian Hu from Zhejiang University, Hangzhou, CN. In an attempt to improve the response rates and lower the toxicity with chimeric antigen receptor T-cell (CAR-T) therapy in B-cell non-Hodgkin lymphoma (B-NHL), the preliminary clinical evaluation of a dual targeting CD19 and CD22 CAR-T construct was presented here. The primary aim of this study was to assess the safety of the dual CAR-T construct. The investigators also compared the efficacy of the dual CAR-T construct to a single-targeting CD19 CAR-T construct. The cytotoxicity of the dual CAR-T construct was assessed in vitro and in mouse models in vivo prior to this in-human preliminary trial. Study design & baseline characteristics N = 20 heavily pre-treated patients with B-cell lymphoma infused with either: CD19/CD22 dual CAR-T construct: n = 11 CD19 CAR-T construct: n = 9 Dual CAR-T construct structure: CAR with antigen recognition domains of both CD19 (anti-CD19 ScFv) and CD20 (anti-CD22 ScFv) 4-1BB costimulatory domain CD3z signaling domain Lymphodepletion: Fludarabine (Flu): 30 mg/m2 1−3 days prior to CAR-T infusion Cytoxan (CTX): 500 mg/m2 2−3 days prior to CAR-T infusion Peripheral blood mononuclear cell (PBMC) collection for CAR-T engineering occurred approximately 11 days prior to infusion Computed tomography (CT) or positron emission tomography (PET)-CT was used for disease assessment every 30 days following CAR-T infusion No statistically significant differences in baseline characteristics between the single CD19 CART and the dual CD19/CD22 CAR-T groups: Characteristic CD19 single CAR-T group (N = 9) Dual CD19/CD22 CAR-T group (N = 11) Median age (range) 47.8 (27−65) years 45.6 (25−65) years Male patients 55.6% 54.5% Disease type     DLBCL 88.9% 81. 8% Burkitt lymphoma 0% 9.1% SLL/CLL 11.1% 0% Lymphoblastic lymphoma 0% 9.1% Prior lines of treatment     2−3 22.2% 27.2% 4−5 33.3% 36.3% > 5 44.4% 36.3% Disease stage     I−II 22.2% 18.2% III−IV 77.8% 81.8% Refractory status at study entry     Primary refractory 44.4% 36.4% Refractory to ≥ 2 lines 55.6% 63.6% Relapse after auto-SCT 22.2% 18.2% Key results Average CAR-T cell infusion dose (range): CD19/CD22 dual CAR-T group: 5.2 x 106/kg (1.1−10 x 106/kg) CD19 CAR-T group: 5.8 x 106/kg (1.6−10 x 106/kg) Comparison: P > 0.05 Average peak CAR-T cell expansion after infusion (10.1 ± 3.32 and 9.2 ± 2.25 days): CD19/CD22 dual CAR-T group: 68.7% (6.9−78.6% in CD3+ T cells) CD19 CAR-T group: 36.8% (3.6−60.9% in CD3+ T cells) Grade 3−5 cytokine release syndrome (CRS): CD19/CD22 dual CAR-T group: 10% CD19 CAR-T group: 33% Neurotoxicity occurred in one patient infused with the dual CD19/CD22 CAR-T construct No patient died due to CAR-T-related adverse events Overall response rates (ORR): CD19/CD22 dual CAR-T group: 90% CD19 CAR-T group: 75% CR rates: CD19/CD22 dual CAR-T group: 70% CD19 CAR-T group: 50% Overall survival rates at Day 90 post infusion: CD19/CD22 dual CAR-T group: 90.0 ± 9.5% CD19 CAR-T group: 55.6% ± 16.6% The OS rates remain stable at Day 250 post infusion Conclusions Promising preliminary in-human results for the dual CD19/CD22 CAR-T construct with B-NHL patients achieving higher CR and ORR, with low severe CRS rates, compared to the standard CD19 single CAR-T construct. More in-human studies and of a larger scale with extended observation periods are needed to further validate these preliminary results.   Source:  Hu Y. et al. Novel CD19/CD22 dual targeting CAR-T cells have prominent anti-tumor activity against relapsed/refractory B-cell lymphoma. Abstract OS20-2: 45th EBMT Annual Meeting, Frankfurt, Germany