Ruella M, Paruzzo L, Chong ER
… +17 more, Chong EA, Landsburg DJ, Nasta SD, Devi P, Michener P, Stella F, Carturan A, Napier EB, Van Deerlin VM, Porazzi P, Levine BL, Frey N, Porter DL, Fraietta JA, Svoboda J, June CH, Schuster SJ
N Engl J Med
· 2026 Jun · PMID 42341302
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BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas. Long-term results and curative potential remain uncertain. METHODS: We...BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas. Long-term results and curative potential remain uncertain. METHODS: We evaluated long-term outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphomas (24 patients with large B-cell lymphoma and 14 with follicular lymphoma) who had been treated with CTL019 (now called tisagenlecleucel) - autologous T cells expressing CD19-directed, 4-1BB-costimulated chimeric receptors. Lymphoma-free survival was defined as the time from the tisagenlecleucel infusion to relapse or lymphoma-related death. The incidence of non-relapse-related death and second primary cancer was estimated with the Aalen-Johansen method. The data-cutoff date was October 1, 2025. RESULTS: At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses had occurred beyond 5.4 years. The 10-year lymphoma-free survival was 32% (95% confidence interval [CI], 14 to 51) among patients with large B-cell lymphoma and 47% (95% CI, 20 to 71) among those with follicular lymphoma. In an analysis that included deaths from any cause, the 10-year progression-free survival was 17% (95% CI, 5 to 34) among patients with large B-cell lymphoma and 29% (95% CI, 9 to 52) among those with follicular lymphoma; the 10-year overall survival was 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively. Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%); no late anemia or thrombocytopenia was observed. A second primary cancer developed in 9 patients (10-year cumulative incidence, 21%). The 10-year non-relapse-related mortality was 18% (14% when deaths related to coronavirus disease 2019 were excluded). Higher CAR-transgene persistence appeared to be associated with long-term response. B-cell aplasia persisted in 44% of patients with a long-term response. CONCLUSIONS: Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).
N Engl J Med
· 2026 Jun · PMID 42341301
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BACKGROUND: Safer, more effective treatment regimens for rifampicin-resistant tuberculosis are needed. METHODS: We conducted a phase 3, open-label, pragmatic, randomized, controlled noninferiority trial in South Africa t...BACKGROUND: Safer, more effective treatment regimens for rifampicin-resistant tuberculosis are needed. METHODS: We conducted a phase 3, open-label, pragmatic, randomized, controlled noninferiority trial in South Africa to assess a 6-month treatment strategy for pulmonary rifampicin-resistant tuberculosis. Participants with pulmonary rifampicin-resistant tuberculosis who were 6 years of age or older were randomly assigned to a regimen consisting of bedaquiline, linezolid, delamanid, and levofloxacin or clofazimine or both for 6 months (trial-strategy group) or the 9-month standard-of-care treatment regimen that was current in South Africa (control group). Persons who were pregnant or breastfeeding and those who had fluoroquinolone-resistant tuberculosis were included in the trial population. Treatment in both groups was adjusted on the basis of results of second-line drug susceptibility testing. The primary efficacy end point was a successful outcome (cure or completion of treatment) at the end of treatment and at 76 weeks after randomization. The noninferiority margin was 10 percentage points. The primary safety end point was an adverse event of grade 3 or higher. RESULTS: Among the 432 persons who were screened, 403 underwent randomization; 203 were assigned to the trial-strategy group, and 200 to the control group. A successful outcome was observed in 174 of 202 participants (86.1%) in the trial-strategy group and in 172 of 200 (86.0%) in the control group. The adjusted risk difference was -0.2 percentage points (95% confidence interval [CI], -6.9 to 6.5; P = 0.001 for noninferiority). Adverse events of grade 3 or higher occurred during treatment in 63 of 202 participants (31.2%) in the trial-strategy group and in 74 of 200 (37.0%) in the control group; 10 participants in each group died. CONCLUSIONS: Among participants in South Africa with rifampicin-resistant tuberculosis, the 6-month trial strategy was noninferior to the standard-of-care strategy with respect to a successful outcome. The safety profiles of the two strategies were similar. (Funded by the U.S. Agency for International Development and others; BEAT Tuberculosis ClinicalTrials.gov number, NCT04062201.).
N Engl J Med
· 2026 Jun · PMID 42341299
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Bundibugyo virus is a relatively rare orthoebolavirus that has caused only two previously recognized disease outbreaks but remains capable of producing severe epidemic disease with substantial mortality. The 2026 outbrea...Bundibugyo virus is a relatively rare orthoebolavirus that has caused only two previously recognized disease outbreaks but remains capable of producing severe epidemic disease with substantial mortality. The 2026 outbreak of Bundibugyo virus disease in the Democratic Republic of Congo has highlighted persistent challenges in the detection of filovirus disease outbreaks, as well as in diagnosis, clinical management, and the public health response, particularly in resource-limited settings. As with other filovirus infections, effective control of the Bundibugyo virus disease outbreak depends on rapid identification of cases, laboratory confirmation of infection, isolation of cases, contact tracing, infection-prevention measures, protection of health care workers, and community engagement. Although no licensed vaccines or approved therapeutics specific to Bundibugyo virus disease are currently available, advances in supportive care have improved outcomes during recent filovirus disease outbreaks. Experimental evidence from studies involving nonhuman primates, serologic investigations with human samples, and monoclonal antibody research suggests that vaccines and therapeutics developed against Ebola virus may provide cross-protective activity against Bundibugyo virus. These observations support prototype-pathogen approaches to preparedness while underscoring the need for continued development of pathogen-specific countermeasures. The current outbreak reinforces the principle that a successful response to filovirus disease requires integration of medical countermeasures, clinical care, surveillance, diagnostics, and coordinated multinational public health operations.