Early Predictors of Severe Cytopenia Post CAR-T for Identification of Patients for Potential Stem Cell Collection
Authors: De Menezes Silva Corraes Andre , Bansal Radhika , Argenau Marques Brunaldi Larissa , Ailawadhi Sikander , Khurana Arushi , Hampel Paul J , Durani Urshila , Dingli David , Hayman Suzanne R. , Kapoor Prashant , Wang Yucai , Binder Moritz , Kenderian Saad S. , Kourelis Taxiarchis , Warsame Rahma M , Bennani N. Nora , Gertz Morie A. , Johnston Patrick B , Ansell Stephen M , Fonseca Rafael , Bergsagel P. Leif , Kumar Shaji Kunnathu , Parrondo Ricardo , Chhabra Saurabh , Lin Yi 
Published: December 2023

Background: Cytopenias are a common complication of and prolonged (beyond month 3 post CAR-T infusion), severe (grade 3 or higher) cytopenias can be difficult to manage. Stem cell boosts have been reported to restore hematopoiesis; however, stem cells would need to be available prior to CAR-T therapy for potential use post CAR-T. Most lymphoma patients and limited number of myeloma patients may have pre-collected stem cells in storage. Identifying patients at high risk for prolonged and severe cytopenia post CAR-T at the time of CAR-T evaluation (baseline), before leukapheresis, can help identify the patients for coordination of stem cell collection during CAR-T manufacturing and increase the likelihood that the collected stem cells would be used. In this study, we aim to identify clinical variables at the time of CAR-T evaluation, prior to leukapheresis, that are associated with severe cytopenias at month 3 post CAR-T infusion and identify patients who could be considered for pre-emptive stem cell collection prior to CAR-T therapy.
Methods: We conducted a retrospective analysis of patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) who received CAR-T products at Mayo Clinic from 01/2016 to 06/2022. Patients with progressive disease in the first year post CAR-T were excluded from the analysis. Baseline (at CAR-T evaluation, prior to leukapheresis) variables were compared between those with and without severe cytopenia at month 3 post CAR-T. Severe cytopenias were defined as hemoglobin (Hg) &lt; 8 g/dL, absolute neutrophil count (ANC) &lt; 0.5 x 10 9/L, and/or platelet count (PLT) &lt; 50 x 10 9/L. Statistically significant variables (p&lt;0.05) by analysis were examined for statistical significance in multivariate analysis (MVA).
Results: Among the 166 patients who received CAR-T (88 NHL, 78 MM) during the study period, 31 (18.67%) had a severe cytopenia at month . Twenty baseline variables were examined; HGB, PLT, ANC, and c-reactive protein (CRP) We devised a cytopenia risk score using 1 point each for Hg&lt;10 or PLT&lt;100k at baseline, with a range of 0 to 2. Demographics and clinical outcome by cytopenia risk score is shown in Table 1B. A higher percentage of patients with a score of 1 or 2 had a severe cytopenia at month 3 (Figure 1). In particular, there was a . In addition
Conclusion: Baseline cytopenias before leukapheresis may identify patients with increased risk for severe cytopenias at month 3 post CAR-T. These patients can have continued slow hematopoietic recovery in the first year. Stem cell collection, if feasible, could be considered before CAR-T to alleviate post-CAR-T severe prolonged cytopenias.