Chimeric antigen receptor T-cell (CAR-T) therapy demonstrates impressive efficacy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T therapy–related severe cytokine release syndrome and neurological toxicity limit its clinical application in R/R DLBCL patients with high tumor burden. Here, we conducted a phase II clinical trial testing the efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin lymphoma patients (NCT03196830). Among the enrolled patients, 10 R/R DLBCL patients with high tumor burden were analyzed. Before CAR-T therapy, 4 were treated with intensive combined chemotherapy (C-CAR-cohort), and 6 were exposed to radiotherapy (R-CAR-cohort). Patients in the R-CAR-T-cohort showed a higher overall response rate (100% vs. 25%, P=0.033) and less severe cytokine release syndrome (0% vs. 100%, P=0.0048) and neurotoxicity (0% vs. 75%, P=0.033) incidences than patients in the C-CAR-T-cohort. Furthermore, one case who responded to CAR-T therapy initially and who suffered a relapse shortly was exposed to radiation and achieved complete remission, with an increase in the number of CAR-T copies detected. This study demonstrates that radiotherapy is an optimal debulking regimen to managing R/R DLBCL patients before CAR-T therapy and a promising alternative salvage therapy for patients who suffer a relapse after CAR-T therapy by fuelling CAR-T copies.
Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Current treatment strategies include the use of growth factors, CD34+-selected stem cell boost, mesenchymal stem cell transfusion, and second allo-HSCT, but these treatments are not effective in all patients. Eltrombopag, an oral thrombopoietin receptor agonist, which showed promising results in severe aplasia anemia, may be an alternative choice for PGF patients. Therefore, we treated 12 patients who responded poorly to standard treatments for secondary PGF after allo-HSCT with eltrombopag. The median duration was 116 (35–1000) days from transplantation to PGF diagnosis and 59 (30–180) days from PGF diagnosis to eltrombopag treatment. Eltrombopag was started at a dose of 25 mg/d for 3 days and then increased to 50 or 75 mg/d. Median treatment duration was 8 (2–23) weeks. Ten patients (83.3%) responded to the treatment: 8 achieved complete response (CR), and the remaining 2 achieved partial response. In the 10 responding subjects, median platelet count was 18 (5–27) × 109/L vs 74 (30–117) × 109/L prior to and after treatment. Neutrophil count was 0.51 (0.28–0.69) × 109/L vs 1.84 (0.78–4.90) × 109/L. Hemoglobin was 88 (63–123) vs 101 (78–134) g/L. In the 8 patients who achieved CR, the time from eltrombopag initiation to achieving CR was 29 (10–49) days; the response lasted until the last follow-up in all 8 CR subjects (10–18 months). The 12-month overall survival rate was 83.3%. There was no treatment-related mortality and no evidence of cataract, thrombosis, or any other grade 3/4 toxicities.
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