Sharma, Shruti

Abstract Introduction: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for treatment response monitoring, risk stratification, and early recurrence detection for patients with lymphoma. Tumor-informed ctDNA testing for detecting molecular residual disease (MRD) is seeing early adoption in this setting, demonstrating technical feasibility and clinical need for personalized monitoring tools. However, the prognostic utility of ctDNA across indolent and aggressive subtypes of lymphoma remains poorly understood. Here, we present real-world data on ctDNA detection and clearance dynamics in patients with various lymphoma subtypes, including patients who are newly diagnosed and those in the relapsed/refractory setting receiving chimeric antigen receptor (CAR)-T therapy. Methods: We performed a retrospective, real-world analysis of ctDNA testing in 148 patients with either B-cell (n=129) or T-cell lymphoma (n=19). Among the 129 patients with B-cell lymphoma, 113 patients had aggressive subtypes (n=84 with DLBCL; n=29 with other), and 16 had indolent lymphoma subtypes. ctDNA was analyzed using a tumor-informed 16-plex mPCR-NGS assay (SignateraTM, Natera, Inc.) from September 2020 - May 2025. Plasma samples (n=1,122; median: 7 per patient, range: 1-31) were collected at baseline, during therapy, at end-of-treatment (EOT), and during follow-up per physician's discretion. ctDNA status at baseline and EOT, and clearance kinetics during first-line (1L) induction therapy were correlated with clinical outcomes. Results: The median patient age was 61 years (range: 18.3–84), and median follow-up was 18.7 months (range: 0.6–54.4 months). Disease stage at diagnosis was available for 139 patients: stage I (n=15, 11%), stage II (n=31, 22%), stage III (n=16, 12%), and stage IV (n=77, 55%). Stage was unknown in 9 patients. Overall, ctDNA detection at baseline was 95.7% (90/94), including 100% in patients with indolent B-cell (11/11), and T-cell lymphomas (6/6), and 94.8% (73/77) in patients with aggressive B-cell lymphomas. Across all subtypes, EOT ctDNA status was strongly prognostic for event-free survival (EFS). Patients with ctDNA-positivity at EOT had significantly worse EFS (HR: 7.33, 95%CI: 2.8-19.18, p<0.0001). In aggressive lymphomas, particularly in DLBCL, ctDNA positivity at EOT was associated with a markedly worse prognosis (Aggressive: HR: 7.69, 95%CI: 2.62-22.56, p=0.0002; DLBCL only: HR: 5.74, 95%CI: 1.71-19.23, p<0.01). Among patients with evaluable ctDNA time points relative to 1L therapy (N=60), ctDNA clearance at any time point during treatment correlated with improved EFS. (HR: 18.55, 95%CI: 4.82-71.32, p<0.0001). All patients who did not clear ctDNA relapsed, yielding a positive predictive value of 100% (11/11); the negative predictive value for those who did clear was 88% (43/49). The remaining six patients turned positive during surveillance prior to relapse. Of 15 patients treated with CAR-T cell therapy, 11 had pre- and post-infusion timepoints for ctDNA analysis. Of these, 82% (9/11) were ctDNA-positive prior to CAR-T, and 55% (5/9) achieved post-infusion ctDNA clearance and a complete clinical response, though one became ctDNA-positive and relapsed (13.3 months post-CAR-T), and another suffered non-disease mortality (22.3 months post-CAR-T). In contrast, all 4 patients remaining ctDNA-positive post-CAR-T relapsed or died within a median of 3.3 months (range: 1.3–6.4 months). Two patients persistently ctDNA-negative remain disease-free. Taken together, the PPV and NPV for 12-month EFS following CAR-T therapy using a single ctDNA timepoint were both 100%. Conclusions: This is the first report of the largest, real-world study evaluating the utility of ctDNA across a broad spectrum of heterogeneous lymphoma subtypes in patients receiving various standard of care therapies. ctDNA status at EOT and on-treatment clearance were strong predictors of clinical outcomes across multiple histological subtypes of lymphoma treated with standard-of-care agents including CAR-T cell therapy. The robustness of these findings across biologically distinct subgroups highlight the broad applicability of ctDNA testing for risk stratification and recurrence monitoring for both aggressive and indolent disease. Further prospective studies are needed to validate these findings.

Abstract Background Acute decompensated heart failure (HF) refractory to medical management deteriorates quickly to cardiogenic shock, ultimately requiring mechanical circulatory support (MCS). These devices aim to provide circulatory support as a bridge to advanced therapies. We report patient outcomes with the latest minimally invasive temporary MCS device: Impella 5.5 with SmartAssist. Methods All patients who underwent Impella 5.5 implantation between January 2020 and December 2023 were analyzed. Duration of Impella support and peri-implant parameters were collected from electronic medical records. ANOVA was performed and utilized a p-value of <0.05 as significant for statistical analysis. Results During our review period, a total of 99 patients were supported with Impella 5.5 in the setting of cardiogenic shock. 92 were bridged to heart transplant (BTT), of which 17 also received combined kidney transplantation. Two underwent durable VAD implantation (BTVAD), and 3 had native heart recovery (BTR) and explant. Two patients died, yielding a survival rate of 98%. For BTT group, the median age was 60 years (52-65) at implant and a median BMI of 27 kg/m² (24-31) with a mean support duration of 29 days (SD ±24). Baseline GFR was 49 mL/min/1.73m² (35-65). In the BTVAD group, the median BMI was 43 kg/m² (39-46) with an average duration of support of 22 days (SD ±8) with a GFR of 55 mL/min/1.73m² (38-73). The BTR group had a median BMI of 29 kg/m² (27-30) with an average duration of support of 15 days (SD ±7) and a lower baseline GFR of 36 mL/min/1.73m² (26 – 37) compared to BTT or BTVAD. The two patients that died were supported for an average of 42 days (SD ±9.2) and expired due to non-candidacy in the setting of newly detected prostate cancer in one patient and multi-organ failure in another. All BTVAD and BTT patients did not have a stroke or major vascular complications before terminal therapy. Conclusion Our center highlights the role of early Impella 5.5 placement in the stabilization of patients in cardiogenic shock, thereby providing both patients and providers time for decision-making while optimizing end-organ perfusion beyond the accepted duration of 14 days.Impella Data - Entire CohortImpella Data - Stratified by Outcome