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95 Prolonged Cytopenia Following CAR T-Cell Therapy in Relapsed/Refractory Multiple Myeloma: A Prospective Comprehensive Biomarker StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 652. Multiple Myeloma: Clinical and Epidemiological: T Cell Redirecting Therapy Outcomes and Associated Complications
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Adverse Events
Saturday, December 9, 2023: 10:30 AM

Xiang Zhou1*, Vivien Wagner2*, Emilia Stanojkovska3*, Christine Riedhammer4*, Xianghui Xiao, MD5*, Mara John3*, Lukas Scheller6*, Umair Munawar7*, Seungbin Han8*, Johannes M Waldschmidt, MD9,10, Max S. Topp, MD11*, Johannes Duell, MD12*, Hermann Einsele, MD, PhD5*, Angela Riedel, PhD3*, Martin Kortüm, MD13* and Leo Rasche, MD5*

1Department of Internal Medicine II, University Hospital Wuerzburg, WüRzburg, Germany
2University of Wurzburg, Wurzburg, Germany
3Mildred Scheel Early Career Center for Cancer Research, University Hospital Wurzburg, Wurzburg, Germany
4Department of Internal Medicine II, University Hospital Wuerzburg, Würzburg, Germany
5Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
6University Hospital Wurzburg, Wuerzbzrg, DEU
7Department of Internal Medicine II, University Hospital of Wuerzburg, Wuerzburg, Germany
8University Hospital Wurzburg, Wuerzburg, DEU
9Department of Internal Medicine II, University of Wuerzburg Medical Center, Wuerzburg, Germany
10Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA
11Medizinische Klinik Und Poliklinik II Universitätsklinikum Wurzburg, Wurzburg, Germany
12Department of Internal Medicine II, Hematology and Oncology, University Hospital Wuerzburg, Wuerzburg, Germany
13Mayo Clinic In Arizona, Scottsdale, AZ


Chimeric antigen receptor (CAR) modified T-cells are leading to a paradigm shift in the treatment of relapsed/refractory (RR) multiple myeloma (MM). A high proportion of patients treated with CAR T-cells, however, experience prolonged cytopenia, with the mechanism remaining poorly understood. Here, we aimed to explore potential biomarkers that might correlate with cytopenia following CAR T-cell therapy in RRMM.


We prospectively collected peripheral blood (PB) of RRMM patients treated with idecabtagen-vicleucel (ide-cel) at the following time points: prior to lymphodepleting chemotherapy (LDC) (baseline), after ide-cel on day 4, 7, 14 and 28, and monthly thereafter. Cytopenia was determined according to the CTCAE version 5.0. Flow cytometry was performed with the following markers: CD45, CD3, CD4, CD8, CD62L, CD45RA, CD19, CD14, CD138, CD38 and a BCMA-CAR-detection marker.


We included 222 PB samples at different sampling time points from 35 RRMM patients, who were pretreated with a median of 5 therapy lines (range 2-10). All patients were triple-class exposed and, 34 (97%) and 9 (26%) patients underwent autologous and allogeneic stem cell transplant (SCT), respectively.

First, we analyzed the relationship between baseline parameters and the duration of grade ≥3 cytopenia after ide-cel (n=35). Notably, patients who received allogeneic SCT or >4 lines of therapy did not develop longer lasting cytopenia than the remaining patients. We found a correlation between the baseline hemoglobin level and the duration of grade ≥3 anemia (r=-0.55, P<0.001). Similarly, low baseline platelet count indicated long duration of grade ≥3 thrombocytopenia (r=-0.48, P=0.003). Moreover, high baseline ferritin level correlated with long duration of grade ≥3 anemia (r=0.52, P<0.001) and thrombocytopenia (r=0.51, P=0.002). Furthermore, the maximum ferritin level after ide-cel was an indicator for long lasting grade ≥3 anemia (r=0.73, P<0.001) and thrombocytopenia (r=0.71, P<0.001). Interestingly, we found significant correlations between the duration of grade ≥3 lymphopenia and baseline CD4+ T-cell frequency (r=0.41, P=0.02), CD8+ T-cell frequency (r=-0.38, P=0.04) and CD4+/CD8+ ratio (r=0.4, P=0.03). Noteworthy, patients with β2-microglobulin level >3.5 mg/l displayed longer duration of grade ≥3 anemia (median: 9 vs 0 day, P=0.007) and neutropenia (median: 43 vs 12 days, P=0.02) compared with the remaining patients, suggesting that high tumor load might be a risk factor for prolonged cytopenia after ide-cel.

Second, we divided the follow-up PB samples (n=187) into two groups: early (<d60) and prolonged (≥d60) cytopenia to account for direct toxic effects related to LDC. A high ferritin level was associated with low hemoglobin level (<d60: r=-0.45, P<0.001, ≥d60: r=-0.62, P<0.001) and low platelet count (<d60: r=-0.58, P<0.001, ≥d60: r=-0.81, P<0.001) in both groups. In prolonged cytopenia (≥d60), lymphocyte count correlated with the T-cell count (r=0.7, P<0.001), suggesting that prolonged lymphopenia was mainly attributed to the reduced T-cell count after ide-cel. Of note, the frequency of naïve CD4+ T-cells (CD3+CD4+CD62L+CD45RA+) positively correlated with neutrophil count (r=0.58, P<0.001), hemoglobin level (r=0.37, P=0.03) and white blood cell count (r=0.5, P=0.002) in the ≥d60 group, suggesting that delayed immune reconstruction with reduced naïve CD4+ T-cells might contribute to prolonged cytopenia after ide-cel. Moreover, in the ≥d60 group, lymphocyte count was related with the frequency of CAR+CD4+ (r=-0.58, P<0.001), CAR+CD8+ (r=0.58, P<0.001), CAR-CD4+ (r=-0.72, P<0.001), CAR-CD8+ (r=0.75, P<0.001) T-cells, as well as the ratios of CAR+CD8+/CAR+CD4+ (r=-0.6, P<0.001) and CAR-CD8+/CAR-CD4+ (r=-0.75, P<0.001).


Here, we present one of the first prospective studies investigating the factors associated with prolonged cytopenia after CAR T-cell therapy in RRMM. High tumor load, preexisting cytopenia and high ferritin level are related with prolonged cytopenia after ide-cel. Delayed immune reconstruction, characterized by reduced naïve CD4+ T-cell count, indicates prolonged cytopenia following ide-cel therapy. Patients with high CD4+/CD8+ ratio are at risk of prolonged lymphopenia (with reduced T-cell count), which may be a risk factor for infectious complications and an issue for subsequent T-cell based immunotherapies.

Disclosures: Waldschmidt: Janssen: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; Takeda: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Research Funding; Pharmamar: Consultancy; Skyline Diagnostics: Consultancy, Research Funding; abc biopply: Consultancy. Topp: AstraZeneca: Consultancy, Research Funding; Roche: Consultancy, Research Funding; GenMab: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Regeneron Pharmaceuticals, Inc.: Consultancy, Research Funding; Takeda: Research Funding; Janssen: Consultancy, Other: Travel support; AbbVie: Consultancy; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding. Duell: MorphoSys AG, Regeneron: Research Funding. Einsele: GlaxoSmithKline: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Takeda: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Amgen: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Janssen: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Sanofi: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Novartis: Honoraria, Other: Consulting or advisory role, Travel support. Rasche: Sanofi: Consultancy, Honoraria; Skyline Dx: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy; Janssen: Consultancy, Honoraria; Roche: Honoraria; GSK: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

*signifies non-member of ASH