#3310 Long-term outcomes of patients developing acute kidney injury after CAR-T cell therapy for relapsed/refractory hematological malignancies

Nephrology Dialysis Transplantation · 2025-10-01

Abstract Background and Aims Acute kidney injury (AKI) occurs in 30% of patients infused with chimeric antigen receptor (CAR) T cells. Despite being a common complication, AKI is usually mild, with rapid recovery in most patients. The purpose of this study was to evaluate long-term kidney function and survival at 2 years after CAR-T cell therapy. Method Medical records of 2-year survivors after CD19-targeted CAR T-cell therapy for refractory/relapsed hematologic malignancies at Vall d'Hebron University Hospital between July 2018 and May 2021 were reviewed. Results From an initial sample of 115 patients infused in that time period, 70 (61%) patients died within 2 years of the CAR-T cell infusion (65 due to progressive disease and 5 due to other complications). Twenty-four patients of the remaining 45 returned to their referral hospital and 21 patients remained alive with complete follow-up at our center. Briefly, mean age of this latter patient population was 57.9 ± 14.8, 52% were male, prior medical history included hypertension in 33% and diabetes in 5% and most (91%) patients had a diagnosis of diffuse large B-cell lymphoma. The CAR-T construct was lisocabtagene maraleucel in 44%, tisagenlecleucel in 33% and axicabtagen ciloleucel in 24%. The most frequent complications were cytokine release syndrome (86%) and neurotoxicity (14%); seven (33%) patients required treatment with tocilizumab. A total of 6 (29%) of the 21 patients developed AKI within the first month after CAR-T cell infusion. None of these patients required renal replacement therapy or ICU admission and AKI was not associated with an increase in mortality after a mean of 56.8 ± 9.4 months of follow-up (P = 0.66). In terms of efficacy, 12 (57%) of these 21 patients achieved a complete response after CAR T-cell therapy and 13 (62%) patients maintained it at 24 months post-infusion. Conclusion Transient AKI development within the first month after CAR T-cell infusion was not associated with increased incidence of mortality with long-term follow-up. Nephrology follow-up is a fundamental part of the multidisciplinary management for this patient population.

CTIM-23. FIRST-IN-HUMAN IMMUNOTHERAPY TARGETING LYMPHOPENIA IN RECURRENT GLIOBLASTOMA MULTIFORM (GBM): NAI AND PD-L1 T-HANK PLUS BEVACIZUMAB WITH COMPLETE RESPONSE

Neuro-Oncology · 2025-11-01 · 1 citations

Abstract BACKGROUND Treatment options for recurrent GBM are limited and associated with high mortality. We hypothesize that current standards of care for GBM induce severe lymphopenia, and by treating lymphopenia (activating NK & T-cells, lymphocytes key to immunogenic cell death), overall survival may be prolonged. Anktiva (nogapendekin alfa-inbakicept, NAI), an IL-15 receptor superagonist, is the first treatment to address lymphopenia by proliferating NK and T-cells. Administered in combination with PD-L1 targeted high-affinity CAR-NK cells (PD-L1 t-haNK) and bevacizumab, treating lymphopenia was hypothesized to elicit tumor response in recurrent GBM METHODS Phase I QUILT-3.078 trial of participants with GBM (IDH WT) who recurred after surgery and temozolomide/XRT. Twelve participants received PD-L1 t-haNK, NAI and bevacizumab, every two weeks, as outpatients. Three patients also received concurrent tumor treating fields. RESULTS At June 4, 2025 data cutoff, 12 participants have received 57 total doses, with 7/12 (58.3%) remaining on therapy. One participant has ongoing radiographic complete response after four doses. In this participant, the Absolute lymphocyte count (ALC) level increased from 170 lymphocytes/µL on entry to ≥1,000 lymphocytes/µL during study treatment and has been maintained. In eight evaluable participants, ALC trend increased from baseline through cycle 4 and was maintained. Median follow-up is 79 days with two deaths on-study, median OS is not reached. Five patients had any SAE, of which one was suspected to be related to bevacizumab (pulmonary embolism), and no SAEs were related to experimental therapy. No CRS or ICANS was observed. CONCLUSIONS These findings provide support that treating lymphopenia and reconstituting lymphocytes (NK & T cells) results in potential OS benefit. This is the first report of disease response in participants with refractory GBM who received orchestrated temporal immunotherapy with CAR-NK cells combined with an IL-15 receptor superagonist and bevacizumab to treat lymphopenia. Updated data to be presented.

Phase 2 trial of personal dendritic cell vaccines in newly diagnosed glioblastoma: 3-year follow-up and correlations with survival

Human Vaccines & Immunotherapeutics · 2025-09-12 · 6 citations

promoter methylation, concurrent dexamethasone dose ≤2 mg, and receipt of six or more TMZ cycles as independent variables. Common features among the seven patients who were progression-free after 3 years were eight vaccine injections, ≤2 mg dexamethasone, age <60 years, and adjuvant TMZ given without concurrent bevacizumab. PFS was encouraging, and the data suggest that OS may be increased by extending vaccine treatment.

Supplementary Table S1 from Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma

2024-01-17

&lt;p&gt;Table S1. Individual listing of clinical trial participants.&lt;/p&gt;

Supplementary Figure S2 from Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma

2024-01-17

&lt;p&gt;Supplementary Figure S2. MRI and CT images of patient P04 with metastatic spinal chordoma in C-spine and lung. C-spine MRI before treatment (A-B) shows C-spine disease (arrows) and 12 months after initiation of high-dose pemetrexed (D-E) shows shrinkage of enhancing tumor on sagittal post contrast T1 sequences (A, D), sagittal T2 (B, E). Chest CT before treatment (C) showed multiple small metastases at baseline axial post contrast sequences that resolved after treatment (F).&lt;/p&gt;

Supplementary Table S6 from Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma

2024-01-17

&lt;p&gt;Table S6. Representativeness of Study Participants&lt;/p&gt;

Supplementary Figure S4 from Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma

2024-01-17

&lt;p&gt;Supplementary Figure S4. Significant cfmiRs found in plasma and tissues. A. Venn diagram showing the cfmiRs differentially expressed detected in plasma of chordoma patients that were also detected in tissue samples from chordoma patients (normalized counts &gt;30). B. Venn diagram showing the common cfmiRs found in plasma samples considering the top 100 cfmiRs most detected, most significant changing, and most upregulated that were identified for chordoma vs normal healthy donors (NHDs). 38 cfmiRs were commonly identified as the most significantly changing, upregulated, and detected in chordoma patients.&lt;/p&gt;

A Microfluidic, Multi-Antibody Cell Capture Method to Evaluate Tumor Cells in Cerebrospinal Fluid in Patients With Suspected Leptomeningeal Metastases

Archives of Pathology & Laboratory Medicine · 2024-05-26 · 3 citations

CONTEXT.—: Leptomeningeal disease (LMD) is a clinical sequela of central nervous system metastasis involving the cerebrospinal fluid (CSF), often seen in late-stage solid tumors. It has a grave prognosis without urgent treatment. Standard of care methodologies to diagnose LMD include CSF cytology, magnetic resonance imaging, and clinical evaluation. These methods offer limited sensitivity and specificity for the evaluation of LMD. Here, we describe the analytic performance characteristics of a microfluidic-based tumor cell enrichment and detection assay optimized to detect epithelial cells in CSF using both contrived samples as well as CSF from patients having suspected or confirmed LMD from carcinomas. OBJECTIVE.—: To demonstrate the feasibility of using a microfluidic, multi-antibody cell capture assay to identify and quantify tumor cells in CSF. DESIGN.—: An artificial CSF solution was spiked with 34 different human carcinoma cell lines at different concentrations and assayed for the ability to detect tumor cells to assess analytic accuracy. Two cell lines were selected to assess linearity, intra-assay precision, interinstrument precision, and sample stability. Clinical verification was performed on 65 CSF specimens from patients. Parameters assessed included the number of tumor cells, coefficient of variation percentage, and percentage of tumor cell capture (TCC). RESULTS.—: Among contrived samples, average tumor cell capture ranged from 50% to 82% (261 of 522; 436 of 531), and coefficients of variation ranged from 7% to 67%. The cell capture assay demonstrated a sensitivity of 92% and a specificity of 95% among clinical samples. CONCLUSIONS.—: This assay demonstrated the ability to detect and enumerate epithelial cells in contrived and clinical specimens in an accurate and reproducible fashion. The use of cell capture assays in CSF may be useful as a sensitive test for the diagnosis and longitudinal monitoring of LMD from solid tumors.

Supplementary Table S2 from Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma

2024-01-17

&lt;p&gt;Table S2. Individual listing of additional chordoma tissue samples collected for miR WTA.&lt;/p&gt;

Supplementary Table S2 from Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma

2024-01-17

&lt;p&gt;Table S2. Individual listing of additional chordoma tissue samples collected for miR WTA.&lt;/p&gt;