Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas.

BACKGROUND: Anti-CD19 chimeric antigen receptor T-cell immunotherapy (CAR-T) is now a standard treatment of relapsed or refractory B-cell non-Hodgkin lymphomas; however, a significant portion of patients do not respond to CAR-T and/or experience toxicities. Lymphodepleting chemotherapy is a critical component of CAR-T that enhances CAR-T-cell engraftment, expansion, cytotoxicity, and persistence. We hypothesized that the lymphodepletion regimen might affect the safety and efficacy of CAR-T. PATIENTS AND METHODS: We compared the safety and efficacy of lymphodepletion using either fludarabine/cyclophosphamide (n = 42) or bendamustine (n = 90) before tisagenlecleucel in two cohorts of patients with relapsed or refractory large B-cell lymphomas treated consecutively at three academic institutions in the United States (University of Pennsylvania, n = 90; Oregon Health & Science University, n = 35) and Europe (University of Vienna, n = 7). Response was assessed using the Lugano 2014 criteria and toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and, when possible, the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. RESULTS: Fludarabine/cyclophosphamide led to more profound lymphocytopenia after tisagenlecleucel infusion compared with bendamustine, although the efficacy of tisagenlecleucel was similar between the two groups. We observed significant differences, however, in the frequency and severity of adverse events. In particular, patients treated with bendamustine had lower rates of cytokine release syndrome and neurotoxicity. In addition, higher rates of hematological toxicities were observed in patients receiving fludarabine/cyclophosphamide. Bendamustine-treated patients had higher nadir neutrophil counts, hemoglobin levels, and platelet counts, as well as a shorter time to blood count recovery, and received fewer platelet and red cell transfusions. Fewer episodes of infection, neutropenic fever, and post-infusion hospitalization were observed in the bendamustine cohort compared with patients receiving fludarabine/cyclophosphamide. CONCLUSIONS: Bendamustine for lymphodepletion before tisagenlecleucel has efficacy similar to fludarabine/cyclophosphamide with reduced toxicities, including cytokine release syndrome, neurotoxicity, infectious and hematological toxicities, as well as reduced hospital utilization.

Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma.

BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.

Survey of patients' views of domiciliary nebuliser treatment for chronic lung disease.

There is some controversy amongst respiratory physicians over the value of domiciliary nebuliser use for chronic lung conditions. Most recommendations for assessment of suitability for this form of treatment rely upon response to lung function tests and reported improvements in exercise ability. Relatively little emphasis has been placed upon the patient view of this therapy. This survey examined the subjective views of patients receiving domiciliary nebulisers regarding this treatment. A postal questionnaire was sent to 82 patients using home nebuliser treatment provided by the respiratory clinic at Whipps Cross University Hospital, London. It consisted of 29 structured questions covering topics of well-being and symptom control, self-confidence, dependency, time and technical issues, as well as side effects and compliance. Most patients surveyed had chronic obstructive lung disease. For almost all sections of the questionnaire patients reported overwhelmingly that the benefits of using a nebuliser outweighed potential disadvantages. The main perceived advantages werethe ability for patients themselves to control symptoms and to be less dependent on General Practitioners, hospitals and carers. Compliance was generally excellent, and the reported side effects were minor and relatively infrequent. The results strongly support the view that nebulisers are helpful in managing chronic lung disease in the community with benefit to patient well-being and potential health cost savings.