Qartemi (varnimcabtagene autoleucel)

We report a case of a 29-year-old woman with refractory stage IV-B THRLBCL treated with anti-CD19 CAR T-cell therapy (varnimcabtagene autoleucel), who achieved an initial response (day +28) but experienced disease progression by day +100 despite robust CAR T-cell expansion. The patient remains in sustained remission, with persistent B-cell aplasia, four years post-intervention. This case provides clinical and pathological evidence supporting the use of immune checkpoint blockade to rescue CAR T-cell efficacy, highlighting the potential of this synergistic approach in THRLBCL and possibly other B-cell malignancies exhibiting similar immune evasion.

Furthermore, CD4+ specific T cells against the CAR19 construct were isolated from the patient's peripheral blood mononuclear cells, showing recognition of the murine single-chain variable fragment peptides presented by human leukocyte antigen class II. This case underscores the need to monitor immune responses in patients before considering subsequent CAR-T infusions to preserve treatment efficacy.Trial registration number NCT03144583.

A pediatric patient with aggressive MDA5+DM-RPILD achieved progressive long-term improvement and immunosuppressant-free remission over 11 months after compassionate use of a CD19 CAR-T cell therapy (ARI-0001).

Our goal is to elucidate the role of procalcitonin (PCT), C-reactive protein (CRP) and ferritin in the context of CRS following CAR T-cell infusion to predict its severity and PICU admission.MethodsProspective observational study (2016-2022) in children and young adult who received CAR T-cell therapy (Tisagenlecleucel/ARI-0001). Biomarkers were higher in those who needed inotropic or respiratory support.ConclusionsPCT levels increase after CAR-T cell therapy in the setting of systemic inflammation and could be a predictor of PICU admission and evolution to death. Further research studying its role in the context of CRS and the differential diagnosis between infection and CRS is needed to better understand the biology of this biomarker and to define its value in clinical practice.

Based on specificity, efficacy, and loss of the target antigen, CARLY3 represents a potential novel CAR treatment for NHL.

We optimized different dual-targeting approaches, including co-transduction of two lentiviral vectors, bicistronic, tandem, loop and pool strategies, based on our academic anti-CD19 (ARI0001) and anti-BCMA (ARI0002h) CAR-T cells. ARI0003 CAR-T cells were effectively manufactured under Good Manufacturing Practice conditions, with reduced risk of genotoxicity compared to other dual-targeting approaches. A first-in-human phase I clinical trial (CARTD-BG-01, NCT06097455) has been initiated to evaluate the safety and efficacy of ARI0003 in NHL.

P2, N=50, Active, not recruiting, Sara V. Latorre | Trial primary completion date: Dec 2023 --> Dec 2024

3%) each received red cells, platelets, G-CSF and romiplostim; majority did not need supportive treatment...mEASIX score may be used as an early predictor of CRS for permissive use of Tocilizumab before onset of severe symptoms. This is the first-in-India industry study evaluating mEASIX and ICAHT in patients treated with CAR-T cell therapy. mEASIX score 1 at D+4 was mildly predictive of CRS. All patients developed ICAHT but only a small number of patients needed supportive treatment.

This is the first-in-India report evaluating hypogammaglobulinemia and infection risk post CAR-T cell infusion. The IVIg usage and documented infections was more in responders. The safety and efficacy outcomes of varnimcabtagene autoleucel (IMN-003A) are consistent with reported outcomes of approved CD19 directed CAR-T cell therapies.

This is the first-in-India industry study evaluating cytokine profile at multiple timepoints before and after var-cel infusion and its correlation with clinical CRS. As per published literature, IL-6 levels were significantly associated with clinical CRS and showed association with peak var-cel expansion. There was a sharp increase in both IL-6 and IL-10 levels in serum post infusion, concurrent with clinical CRS prior to peak var-cel expansion.

The Bengaluru Score is probably the first predictive prognostic score for clinical efficacy outcomes and is based on multivariant statistical analysis in the discovery cohort of patients in the IMAGINE study integrating clinical, laboratory and translational data with a very high sensitivity, specificity and accuracy. The score highlights the role of overall T cell expansion in the final product for B-ALL (but not the T N+CM subsets on its own) and for B-NHL, disease burden and haematological reserve. This suggests that earlier use of varnimcabtagene autoleucel may positively influence efficacy outcome but needs to be proven in the real-world setting.

B-ALL pt received Dasatinib, Inotuzumab and CNS prophylaxis. Preparative conditioning regimen for these 4 patients were: Fludarabine-Cyclophosphamide (n=1), with Rituximab (n=2) and Rituximab with Nivolumab (n=1)... Reinfusion of varnimcabtagene autoleucel (IMN-003A) is feasible, safe and well tolerated. Preparative conditioning regimen for reinfusion needs personalization guided by CAR persistence, disease biology (CD20, PDL1 expression) and haematological reserve. After reinfusion, prolonged B cell aplasia was observed with 100% ORR at D+28 in evaluable pts.