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) < 8 g/dL, absolute neutrophil count (ANC) < 0.5 x 10 9/L, and/or platelet count (PLT) < 50 x 10 9/L. Statistically significant variables (p<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<10 or PLT<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.

Ailawadhi:AbbVie, Amgen, Ascentage, BMS, Cellectar, GSK, Janssen, Pharmacyclics, Sanofi: Research Funding; Beigene, BMS, Cellectar, GSK, Janssen, Pfizer, Regeneron, Sanofi, Takeda: Consultancy. Dingli:Alexion (AstraZeneca); Apellis Pharmaceuticals; BMS; GSK; Janssen; Novartis; Sanofi; Takeda: Consultancy; Apellis: Consultancy; BMS: Consultancy; Janssen: Consultancy; K-36 Therapeutics: Research Funding; Novartis: Consultancy; Sanofi: Consultancy; Sorrento: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; BioCryst: Consultancy. Wang:Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innocare: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Novartis: Research Funding; Genentech: Research Funding; Genmab: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Kenderian:Torque: Consultancy; Luminary therapeutics: Other: scientific advisory board ; MustangBio: Patents & Royalties; Sendero: Patents & Royalties; Mettaforge: Patents & Royalties; Lentigen: Research Funding; Tolero/Sumtomo: Research Funding; Morphosys: Research Funding; LEAHLabs: Consultancy, Current equity holder in private company, Research Funding; CapstanBio: Consultancy, Other: Scientific advisory board; Humanigen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Juno/BMS: Other: Membership on an entity's board of directors or advisory committees, Research Funding; Kite/Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding, Speakers Bureau. Bennani:Kymera: Other: Advisory board; No personal compensation; Secura Bio: Other: Advisory board; No personal compensation; Affimed: Other: Advisory board; No personal compensation; Astellas Pharma: Other: Advisory board; No personal compensation; Acrotech: Other: Advisory board; No personal compensation; Acrotech: Other: Scientific Advisory Committee, No personal compensation . Gertz:AbbVie: Other: Data Safety Monitoring board; Ionis/Akcea, Prothena, Sanofi, Janssen, Aptitude Healthgrants, Ashfield, Physicians Education Resource, Research to Practice, Johnson & Johnson, and Celgene: Consultancy; i3HEalth: Other: For development of educational material; Juno Pharmaceutics, and Sorrento Therapeutics: Other: Meetings. Ansell:Seagen Inc: Other: Contracted Research; Regeneron Pharmaceuticals Inc: Other: Contracted Research; Pfizer, Inc: Other: Contracted Research; Takeda Pharmaceuticals USA Inc: Other: Contracted Research; Affirmed: Other: Contracted Research; Bristol-Myers Squibb: Other: Contracted Research; ADC Therapeutics: Other: Contracted Research. Fonseca:Pharmacyclics: Consultancy; Millenium: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Juno: Consultancy; Regeneron: Consultancy; FISH: Patents & Royalties: FISH; BMS (Celgene): Consultancy; Kite: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; AMGEN: Consultancy; AZBio: Membership on an entity's Board of Directors or advisory committees; Antegene: Membership on an entity's Board of Directors or advisory committees; Binding Site: Consultancy; Bayer: Consultancy; Aztrazenica: Consultancy; Adaptive Biotechnologies: Consultancy; AbbVie: Consultancy. Bergsagel:Aptitude Health: Honoraria; Novartis: Patents & Royalties: Royalty for hCRBN mice; Mayo Clinic: Patents & Royalties: Royalty for hCRBN and Vk*MYC mice; Pfizer: Research Funding; Janssen: Consultancy; Salarius: Consultancy; CellCentric: Consultancy; Omeros: Consultancy; Radmetrix: Consultancy.

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2023
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