End Of Clinical Course Research Articles

Cytokine Profile Following Varnimcabtagene Autoleucel (IMN-003A) in Patients with Relapsed Refractory B Cell Malignancies in the First-in-India Industry Phase-2 Study (IMAGINE)

Background: Varnimcabtagene autoleucel (Var-cel, IMN-003A) is an autologous CD19 directed CAR-T cell product with a 4-1BB co-stimulatory domain and a non-FMC63 murine single chain variable fragment (A3B1 binder), manufactured in India, tested in the IMAGINE study (CTRI/2022/03/041162), a phase-2 clinical trial for patients (pts) with relapsed and/or refractory B cell malignancies. This abstract evaluates the cytokine profile and its correlation with safety outcomes and CAR-T expansion following var-cel infusion. Methods: Serum was collected pre-infusion and upto 13 timepoints post infusion as per study schedule for evaluating cytokine levels. Nine cytokines (IFN-g, TNF-α, IL-1β, IL-2, IL-7, IL-8, IL-10, IL-15 and MCP-1) were measured using a multiplexed kit on the Magpix platform. IL-6 level was measured using electrochemiluminescence immunoassay (ECLIA). Safety and adverse event data were collected for analysis along with measuring various cytokine levels in the serum. CAR-T persistence post infusion was monitored using ddPCR. Results: 24 patients (pts) were infused with var-cel in the IMAGINE study. Var-cel levels in peripheral blood post-infusion were measured at multiple timepoints for all infused pts using ddPCR platform. The var-cel levels peaked (Tmax) at a median of 10 days post infusion (D+10; range: 10 - 28 days) with median Cmax of 125,242 (range 18,256 - 413,968 copies/µg genomic DNA). The median duration of persistence was 56 days with persistent CAR seen in 3 pts at last follow-up. Adverse events of special interest (AESIs) reported were CRS (Grade [G] 1 62.5%; G3+ 4.2%; overall 66.7%) and ICANS (G1 4.2%; G3+ 0%; overall 4.2%). The median onset of CRS at D+5, 5 days before the median var-cel Tmax of D+10. The median duration for CRS was 3 days. No G3+ ICANS was reported. Serum IL-6 levels peaked at a median of D+7 post infusion and reached above 40 pg/mL for 13 pts, all of whom experienced CRS. All eight pts with no CRS had peak IL-6 levels below 40 pg/mL. Despite this significant association with CRS (p<0.001, Man-Whitney test) and published causation, IL-6 level peaked towards the end of clinical course of CRS manifestation, but usually at or before peak var-cel expansion (Tmax). Interestingly, the increase in IL-6 levels tended to begin early and persist longer for some B-NHL patients compared to B-ALL patients. Preliminary multiplexed cytokine analysis for evaluated pts (n=6) indicated that IFN-γ, TNF-α, IL-1β, IL-2, IL-7, IL-8 remained within published physiological limits for most patients at all timepoints (except one pt with highest levels at screening). One patient showed mild increase in IFN-γ (peak 50.88 pg/mL) and two pts showed mild increase in IL-8 around D+4 to D+7 (peak 47.71 pg/mL). IL-15 and MCP-1 levels were relatively higher (>2 fold) from D0 to D+7 post infusion, compared to the screening timepoint, consistent with the duration of CRS. Only IL-10, an anti-inflammatory and cytokine synthesis inhibitory factor stood out having a sharp peak (median: 230 pg/mL) for all six patients at D+4 to D+10, consistent with the timeline for end of CRS and before var-cel Tmax. Occasional pt with no clinical CRS also showed IL-10 peak. Updated cytokine profile data shall be presented at the meeting. Conclusions: 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. A further detailed study of cytokine profile following var-cel infusion shall help prognosticate safety outcomes.

A quasi-experimental study of the effect of teaching Orem's self-care model on nursing students' clinical performance and patient satisfaction.

AimsThis study aims to determine the effect of teaching Orem's self‐care model on nursing students’ clinical performance and patient satisfaction.DesignThe study was a quasi‐experimental, non‐randomized, two‐group design with posttest.MethodsIn this quasi‐experimental study, 66 nursing students were selected via convenience sampling method. The intervention group was trained based on Orem's self‐care model and the control group based on the routine nursing process method. Both groups cared patients for a week. Students’ performance was evaluated during the clinical course by performance observation checklist and patient satisfaction was assessed at the end of clinical course using patient satisfaction form. Data were analysed in SPSS software using chi‐squared, Fisher Exact test, Mann–Whitney, t test and two‐way ANOVA.ResultsClinical performance evaluation mean score in the intervention group was significantly higher than that of the control group. However, patient satisfaction scores in both the control group and intervention group did not show statistically significant differences. Orem's self‐care model showed a 23% improvement in students’ performance. It is recommended to use Orem's self‐care model for undergraduate courses, especially in clinical training.

Cytomegalovirus infection is not necessarily a poor prognostic factor in adult T-cell leukemia/lymphoma

The relationship between cytomegalovirus (CMV) antigenemia and the clinical course was examined in 57 patients with adult T-cell leukemia/lymphoma (ATLL). All patients included had the acute/lymphoma type of ATL according to the criteria of the Japan Lymphoma Study Group (LSG). CMV antigenemia was assessed on admission and at the time when the patients had fever higher than 37. 5 degrees C, which did not respond to antibiotics for longer than 3 days. The incidence of CMV antigenemia was 44%. Approximately 90% of patients with CMV antigenemia died of infections with viruses, bacteria, and/or fungi, while approximately 40% of patients without CMV antigenemia died of deterioration of ATLL (P<0.0001). In this study, the patients with CMV antigenemia tended to survive longer than those negative for it (321.4 days vs. 266.2 days), although there was no statistical significance (P=0.09). Kaplan-Meier analysis revealed that CMV antigenemia was not a poor prognostic factor. When the disease status of ATLL was evaluated by thymidine kinase (TK) and soluble interleukin 2 receptor (sIL-2R), both had lower titers during CMV antigenemia (TK: P=0.01, sIL-2R: P=0.03, respectively). Therefore, CMV infections in ATLL patients seemed to have bimodal meanings; CMV infection at the end of clinical course were life-threatening, but infection during the first half of clinical course seemed to suppress ATLL activity and to contribute to the longer survival of the patients.