Prognostic Impact of 18F-FDG PET/CT in Patients With Aggressive B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T Cells.

PURPOSE OF THE REPORT: We aimed to evaluate the role of 18F-FDG PET/CT in predicting patient outcome following chimeric antigen receptor T (CAR T) cells infusion in aggressive B-cell lymphoma. METHODS: 18F-FDG PET/CT data before leukapheresis, before CAR T-cell infusion and 1 month (M1) after CAR T-cell infusion, from 72 patients were retrospectively analyzed. SUVmax, total lesion glycolysis (TLG), metabolic tumor volume (MTV), and parameters describing tumor kinetics were calculated for each 18F-FDG PET/CT performed. The aim was to evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters for predicting progression-free survival (PFS) and overall survival (OS) following CAR T-cell therapy. RESULTS: Regarding PFS, ∆MTVpre-CAR and ∆TLGpre-CAR were found to be more discriminating compared with metabolic parameters at preinfusion. Median PFS in patients with a ∆MTVpre-CAR of less than 300% was 6.8 months (95% confidence interval [CI], 2.8 months to not reached) compared with 2.8 months (95% CI, 0.9-3.0 months) for those with a value of 300% or greater (P = 0.004). Likewise, median PFS in patients with ∆TLGpre-CAR of less than 420% was 6.8 months (95% CI, 2.8 months to not reached) compared with 2.7 months (95% CI, 1.3-3.0 months) for those with a value of 420% or greater (P = 0.0148). Regarding OS, metabolic parameters at M1 were strongly associated with subsequent outcome. SUVmax at M1 with a cutoff value of 14 was the most predictive parameter in multivariate analysis, outweighing other clinicobiological variables (P < 0.0001). CONCLUSIONS: Disease metabolic volume kinetics before infusion of CAR T cells seems to be superior to initial tumor bulk itself for predicting PFS. For OS, SUVmax at M1 might adequately segregate patients with different prognosis.

Commercial anti-CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center.

Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P < .001). Likewise, the only factor associated with a shorter OS was CRP >30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.

Virological outcome at week 48 of three recommended first-line regimens using ultrasensitive viral load and plasma drug assay.

OBJECTIVES: To describe the virological and pharmacological outcomes of three different recommended once-daily first-line regimens in a cross-sectional analysis within an observational cohort using ultra-sensitive HIV quantification. PATIENTS AND METHODS: We enrolled all HIV-1-infected patients who initiated tenofovir/emtricitabine with efavirenz, darunavir/ritonavir or atazanavir/ritonavir as a first-line regimen between 1 November 2010 and 30 June 2012. An ultrasensitive viral load (VL) assay was performed and plasma drug concentrations at 24 h (C24) were determined at Week (W) 4, W12, W24, W36 and W48. RESULTS: Sixty patients initiated efavirenz, 81 darunavir/ritonavir and 27 atazanavir/ritonavir. A higher proportion of patients with a VL >100 000 copies/mL received darunavir/ritonavir (P = 0.022). At W48, 89%, 85% and 88% of the patients had a VL <50 copies/mL, 69%, 73% and 79% had a VL <20 copies/mL and 45%, 48% and 54% had a VL <1 copy/mL using the ultrasensitive assay in the efavirenz, darunavir/ritonavir and atazanavir/ritonavir groups, respectively. Patients with a detectable VL signal at W48 had a higher baseline VL than those with no detectable VL signal (P = 0.0001). A total of 92%, 93% and 91% of the efavirenz, darunavir and atazanavir C24 values were above the respective effective cut-offs. CONCLUSIONS: In this observational cohort, the choice of the regimen was related to the physicians' preferences and the patients' characteristics. The proportion of patients reaching VL <1 copy/mL at W48 was similar in the three regimens and was not associated with drug concentrations.

Generic antiretroviral drugs in developing countries: friends or foes?

Although second-line generic antiretroviral drugs are of great value in developing countries, there are concerns regarding their quality. We studied a generic Lopinavir/ritonavir (200/50  mg; Arga-L, India) marketed in the Republic of Congo but not prequalified by WHO. Despite adequate quantitative and qualitative drug content, Arga-L had a bio-availablility of 10% compared with Kaletra. To avoid selection of drug-resistant HIV, rigorous pharmacological monitoring of generic drugs not prequalified by WHO must be a priority.