Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Adult, Epidemiology, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Diseases, Real-world evidence, Aggressive lymphoma, Lymphoid Malignancies, Adverse Events, Study Population, Human
Adults with R/R LBCL after ≥2 lines of systemic therapy who received CART as standard of care between May 2020 and December 2023 across all 7 Dutch CART centers were included. HT score was calculated per the original report, including absolute neutrophil count (ANC), hemoglobin (Hb), platelet count, C-reactive protein (CRP) and ferritin, determined prior to lymphodepleting chemotherapy. A high HT score was defined as HT score ≥2 (HThigh). Patients with at least 3 out of 5 laboratory parameters were included. Missing laboratory values were imputed with predictive mean matching and pooled results are reported. Endpoints included clinically significant neutropenia (ANC <500/µl, ≥14 days between day 0-60), severe infections, progression-free survival (PFS) and overall survival (OS). Infections between infusion and day +90 were graded severe (grade ≥3) when requiring intravenous anti-infective agents and/or hospitalization.
Of the 244 identified patients, 239 patients had ≥3 laboratory parameters available, with 141 complete cases. The median age was 62 [20-84] years. The majority of patients were diagnosed with LBCL (52%), followed by transformed Follicular Lymphoma (31%). Median number of prior lines of therapy was 2 (range 2-6) and 29% received a previous stem cell transplantation. Median HT score was 2 (IQR 1-3], with 163 patients (68%) classified as HThigh.
Severe neutropenia (ANC <500/µl) after CART was common (n = 202/239, 85%), but only 50 patients (21%) experienced a duration of ≥14 days. Granulocyte colony-stimulating factor (G-CSF) was administered in 113 patients (47%). A higher HT score was associated with a higher risk of clinically significant neutropenia (continuous HT: OR 1.61; 95% CI [1.24 – 2.08]; p < 0.01), and had a fair predictive performance (AUC 0.70). This increased risk was also observed in HThigh patients (binary HT: OR 2.39; 95% CI [1.10 – 5.20]; p = 0.03).
Any grade infection was seen in 73/193 patients (38%), with severe infections in 38 patients (20%). Incidence was comparable to previous reports. Both the continuous and the binary HT score were not associated with severe infections in our cohort (p = 0.10 and p = 0.46). CRS and ICANS grade ≥2 were apparent in 118/239 patients (49%) and 96/239 patients (40%), respectively. HT score was not associated with developing CRS or ICANS grade ≥2 (p = 0.38 and p = 0.16).
Nevertheless, HT score was significantly associated with OS and PFS (HR 1.55; 95% CI [1.32 – 1.81]; p < 0.01 and HR 1.33; 95% CI [1.16 – 1.51]; p < 0.01, respectively). In detail, Hb, CRP and ferritin were univariably associated with survival (all p < 0.01), suggesting the potential adverse prognostic effect of a limited bone marrow reserve and high baseline inflammation. Additionally, patients classified as HThigh had a nearly 3-fold increased risk of death compared to HTlow patients (OS: HR 2.83; 95% CI [1.64 – 4.90]; p < 0.01 and PFS: HR 1.82; 95% CI [1.09 – 3.04]; p = 0.02).
In conclusion, the HT score identifies patients at risk for severe neutropenia and reduced survival, but not for severe infections after CART in this population-based, real-world cohort. This study underscores the potential of the HT score, yet emphasizes the need for further optimalization before broad implementation and guidance of antibiotic prophylaxis strategies.
Disclosures: De Boer: Siemens: Research Funding. Niezink: Genentech: Research Funding; Siemens: Research Funding. Kuipers: Galapagos: Honoraria. Kersten: Miltenyi Biotec: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Kite, a Gilead company: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding. Jak: Kite, a Gilead company: Honoraria; BMS/Celgene: Honoraria; Janssen: Consultancy; Novartis: Research Funding. van der Poel: Kite, a Gilead company: Honoraria; Takeda: Honoraria. Vermaat: Secura Bio: Consultancy. van Meerten: Jansen: Consultancy; Genentech: Research Funding; Eli Lilly: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Siemens: Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding.
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