CAR T-cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real-life results of the LOC network.

The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T-cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR-T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty-seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T-cells (tisa-cel: N = 16, axi-cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow-up after leukapheresis was 20.8 months. The best response after CAR-T cells was complete response in 16 patients (64%). One-year progression-free survival from leukapheresis was 43% with a plateau afterward. One-year relapse-free survival was 79% for patients in complete or partial response at CAR T-cell infusion. The median overall survival was 21.2 months. Twenty-three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T-cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p < 0.001). This series represents the largest cohort of PCNSL treated with CAR T-cells reported worldwide. CAR T-cells are effective in relapsed PCNSL, with a high rate of long-term remission and a reassuring tolerance profile. The results seem clearly superior to those usually observed in this setting.

Utilization of intravenous or subcutaneous immunoglobulins in secondary immune deficiency (ULTIMATE): A retrospective multicenter study.

INTRODUCTION: We conducted a retrospective multicenter cohort study of patients receiving Immunoglobulin replacement therapy (IgRT) for secondary immune deficiency (SID) during 2012. METHODS: Data were retrospectively collected from the first dose of Ig administered in 2012 to 1 year afterward in terms of the indication for IgRT, as well as efficacy and safety. RESULTS: In total, 16 hospitals participated in the study, and 368 patients were included. Indications for IgRT were non-Hodgkin lymphoma (82 [22.3%] patients), multiple myeloma (76 [20.7%]), chronic lymphocytic leukemia (64 [17.4%]) and other (79 [21.5%]). Only 89 (24.2%) patients received IgRT according to 2011 European Medical Agency (EMA) recommendations; 196 (53.3%) received prophylactic antibiotics and 262 (76.2%) had an IgG level < 4 g/L before IgRT initiation. CONCLUSION: In this study, whatever the criteria, only 24.2% of patients with SID who received IgRT met EMA recommendations, which suggests a misuse of IgRT in SID.

Impact of plerixafor (mozobil) on hospital efficiency: A single center experience.

Plerixafor (Mozobil) in combination with granulocyte colony-stimulating factor (G-CSF) has shown to increase mobilization of peripheral blood stem cells (PBSC) as compared to G-CSF alone in patients undergoing autologous stem cell transplantation (ASCT). However, up to 25% of patients treated with G-CSF alone still fail mobilization. Adding plerixafor to poor mobilizers allows to rescue these patients from mobilization failure and to reduce the number of apheresis sessions. The goal of this retrospective study was to capture the impact of plerixafor on treatment outcome and on apheresis department efficiency. The latter was measured in terms of time-slots lost, that is, the number of apheresis sessions scheduled but not carried out due to poor mobilization, and the number of elective apheresis sessions performed for patients undergoing extracorporeal photopheresis (ECP). Hospital records of patients treated before and after introduction of plerixafor were collected and analyzed. With plerixafor, the mobilization failure rate dropped from 12% to 4% and the mean number of time-slots lost per patient dropped from 1.39 to 0.89. Additional drug costs due to plerixafor were partially balanced by a reduction in apheresis sessions, resulting in an additional cost of 759€ per ASCT candidate. More importantly, with the use of plerixafor, the availability of time-slots turned from erratic to predictable such that freed capacity could be dedicated to other apheresis procedures. As a result, the number of ECP sessions increased from 0 in 2005 to 685 sessions in 2014.

A phase II Bayesian sequential clinical trial in advanced Waldenström macroglobulinemia patients treated with bortezomib: interest of addition of dexamethasone.

In patients with advanced Waldenström macroglobulinemia (WM), overall response rate (ORR) and median progression-free survival (PFS) achieved with bortezomib alone and bortezomib rituximab combination were 27-85% and 7.9 months, and 81% and 16.4 months, respectively. We checked the role of dexamethasone in combination with bortezomib by enrolling in a phase II trial 34 patients with relapsed/refractory WM. Bortezomib (1.3 mg/m2 IV D1, 4, 8, and 11 every 21 days) was used for six cycles. In non-responding patients, dexamethasone (20 mg daily for two days) was added to each infusion after the second cycle. After two cycles, the Bayes estimated ORR was 43.2 (95% Credible Interval: 28.0-59.1%) using the informative prior. Two-year survival rate was 84.0% and the median PFS 15.3 months without difference between patients treated with or without dexamethasone. We conclude that dexamethasone must be associated to bortezomib-based regimen.

Efficacy and long-term toxicity of the rituximab-fludarabine-cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia is generally treated with alkylating agents, purine analogs and monoclonal antibodies, alone or in combination. We report the outcomes of 82 patients (median age 61 years) treated with the RFC combination. Twenty-five patients were treatment-naive. RFC was administered every 4 weeks, for a median of five cycles. At treatment discontinuation, the overall response rate was 85.4%. The responses improved after treatment discontinuation in 25 patients, with a median time to best response achievement of 10.8 months, raising the major response rate (PR, VGPR and CR) from 64.6% to 76.8%. With a median follow-up of 47 months, the median progression-free survival time had not been reached (67% PFS at 48 months) and was influenced by age and treatment status before RFC. Likewise, the median time to next therapy had not been reached. Two cases of myelodysplastic syndrome/AML and 3 cases of transformation to aggressive lymphoma occurred. Thirteen patients died. The 3-year overall survival rate was 90%. Long-lasting cytopenias occurred in 19 patients. The RFC combination thus gave a high response rate and durable responses, even in heavily treatment-experienced patients. The high incidence of long-lasting cytopenia might be reduced by giving fewer courses and thereby minimizing myelotoxicity. Am. J. Hematol. 91:782-786, 2016. © 2016 Wiley Periodicals, Inc.