Contributions
Abstract: EP744
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Chimeric antigen receptor (CAR) T-cells therapy targeting CD19 is emerging as a promising treatment for patients affected by relapsed/refractory Diffuse Large B Cell Lymphoma (DLBCL) and Primary Mediastinal B Cell Lymphoma (PMBCL). Cytokine Release Syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have been described as the most common toxicities in the first 14 days after CAR T-cells infusion. During follow-up, patients are often suffering from long-lasting cytopenia and infections, the causes of long-term toxicity have not yet been clearly explained.
Aims
To investigate the frequency of infections and cytopenia after CAR T-cells infusion and whether clinical characteristics, laboratory data and bone marrow (BM) function could be associated to the risk of long term toxicity
Methods
Consecutive patients receiving CAR T-cells at Fondazione IRCCS Istituto Nazionale dei Tumori in Milano between 2019 and 2020 with at least 3 months of follow-up were included in the study. Clinical and laboratory data were collected from electronic medical records; patients with persistent severe cytopenia (i.e. ANC < 1000/μl and/or PLT < 50000/μl) at 3 months of follow-up were investigated with BM biopsy, cytogenetic, FISH analysis and NGS studies.
Results
Forty-six patients receiving anti-CD19 CAR T-cells affected by DLBCL (n=34) and PMBCL (n=12) were included in this analysis. Median age was 49 years (range, 21-72) and median follow-up was 9 months (range, 1-21). Four patients died before 3 months of follow-up.
All patients received anti Peumocystis jiroveci, antiviral and antifungal prophylaxis starting at lymphodepletion (LD) and continued until CD4 count > 200/μl. Overall in the first 3 months we observed 21 infectious events in 15/42 patients (33%), including bacterial (n=14), fungal (n=5) and viral (n=2) infections. CRS of any grade after CAR T-cells infusion, the use of steroids and tocilizumab were significantly associated with an increased risk of infections at 3 months.
Severe cytopenia was observed in 11/42 (26%) of patients at 3 months and in 9/31 (29%) at 6 months. Neutropenia pre CAR T-cells infusion, a peak of ferritin > 5 times upper value (i.e > 1375 ng/ml) and female sex were significantly associated with a higher incidence of cytopenia at 3 months whereas neutropenia before LD was associated with cytopenia at 6 months
Three months after CAR T-cells BM examination was performed in 6/11 of patients with severe cytopenia and in 10 relapsed/refractory patients without cytopenia during work-up for a new treatment. In cytopenic patients, BM histologic examination showed dysmyelopoiesis (n=1), hypocellular marrow (n=3) and normal morphology (n=2), cytogenetic analysis was normal and FISH analysis for del5q and -7 were negative. NGS study was performed in 4 patients showing a clonal hematopoiesis of indeterminate potential (CHIP) due to DNMT3A mutations with a VAF of 2% and 9% in two of them. BM of 10 relapsed patients without cytopenia were histologically normal.
Conclusion
Three months after CAR T-cells infusion almost a third of patients experienced one or more infectious events and cytopenia was present in a quarter of patients. CRS and consequent treatment seemed to be factors predisposing to infections whereas cytopenia seemed to be associated to neutropenia pre CAR T-cells or high ferritin peak. At 3 months a limited occurrence of myelodysplastic features were observed in BM analyzed. A larger cohort of patients and a longer follow-up is required to confirm these data.
Keyword(s): CAR-T, Diffuse large B cell lymphoma, Infection, Toxicity
Abstract: EP744
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Chimeric antigen receptor (CAR) T-cells therapy targeting CD19 is emerging as a promising treatment for patients affected by relapsed/refractory Diffuse Large B Cell Lymphoma (DLBCL) and Primary Mediastinal B Cell Lymphoma (PMBCL). Cytokine Release Syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have been described as the most common toxicities in the first 14 days after CAR T-cells infusion. During follow-up, patients are often suffering from long-lasting cytopenia and infections, the causes of long-term toxicity have not yet been clearly explained.
Aims
To investigate the frequency of infections and cytopenia after CAR T-cells infusion and whether clinical characteristics, laboratory data and bone marrow (BM) function could be associated to the risk of long term toxicity
Methods
Consecutive patients receiving CAR T-cells at Fondazione IRCCS Istituto Nazionale dei Tumori in Milano between 2019 and 2020 with at least 3 months of follow-up were included in the study. Clinical and laboratory data were collected from electronic medical records; patients with persistent severe cytopenia (i.e. ANC < 1000/μl and/or PLT < 50000/μl) at 3 months of follow-up were investigated with BM biopsy, cytogenetic, FISH analysis and NGS studies.
Results
Forty-six patients receiving anti-CD19 CAR T-cells affected by DLBCL (n=34) and PMBCL (n=12) were included in this analysis. Median age was 49 years (range, 21-72) and median follow-up was 9 months (range, 1-21). Four patients died before 3 months of follow-up.
All patients received anti Peumocystis jiroveci, antiviral and antifungal prophylaxis starting at lymphodepletion (LD) and continued until CD4 count > 200/μl. Overall in the first 3 months we observed 21 infectious events in 15/42 patients (33%), including bacterial (n=14), fungal (n=5) and viral (n=2) infections. CRS of any grade after CAR T-cells infusion, the use of steroids and tocilizumab were significantly associated with an increased risk of infections at 3 months.
Severe cytopenia was observed in 11/42 (26%) of patients at 3 months and in 9/31 (29%) at 6 months. Neutropenia pre CAR T-cells infusion, a peak of ferritin > 5 times upper value (i.e > 1375 ng/ml) and female sex were significantly associated with a higher incidence of cytopenia at 3 months whereas neutropenia before LD was associated with cytopenia at 6 months
Three months after CAR T-cells BM examination was performed in 6/11 of patients with severe cytopenia and in 10 relapsed/refractory patients without cytopenia during work-up for a new treatment. In cytopenic patients, BM histologic examination showed dysmyelopoiesis (n=1), hypocellular marrow (n=3) and normal morphology (n=2), cytogenetic analysis was normal and FISH analysis for del5q and -7 were negative. NGS study was performed in 4 patients showing a clonal hematopoiesis of indeterminate potential (CHIP) due to DNMT3A mutations with a VAF of 2% and 9% in two of them. BM of 10 relapsed patients without cytopenia were histologically normal.
Conclusion
Three months after CAR T-cells infusion almost a third of patients experienced one or more infectious events and cytopenia was present in a quarter of patients. CRS and consequent treatment seemed to be factors predisposing to infections whereas cytopenia seemed to be associated to neutropenia pre CAR T-cells or high ferritin peak. At 3 months a limited occurrence of myelodysplastic features were observed in BM analyzed. A larger cohort of patients and a longer follow-up is required to confirm these data.
Keyword(s): CAR-T, Diffuse large B cell lymphoma, Infection, Toxicity