The 49th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Award Winners (O001-O008)
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November 9, 2023
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0 min
Improved COVID-19 Outcomes and CAR T-Cell Therapy Insights from EBMT 2023
Overview
Recent EBMT registry data demonstrate improved survival in allogeneic stem cell transplant patients with COVID-19 over time, with higher mortality linked to CMV seropositivity and other risk factors. Additionally, a 5-year follow-up of CD19 CAR T-cell therapy in relapsed/refractory CLL reveals durable responses and factors influencing duration of response.
Background
Allogeneic hematopoietic stem cell transplant (allo-HCT) recipients are at high risk for severe COVID-19 outcomes. Early pandemic data showed nearly 30% mortality, but advances in management and viral variants have influenced outcomes. CD19 CAR T-cell therapy is an emerging treatment for relapsed/refractory B cell malignancies, including chronic lymphocytic leukemia (CLL), with ongoing studies assessing long-term efficacy and predictors of response.
Data Highlights
| Parameter | Value |
|---|---|
| Number of allo-HCT patients with COVID-19 | 986 |
| Median age (years) | 50.3 (range 1.0–80.7) |
| Median time from HCT to COVID-19 diagnosis (months) | 20 (range 0.0–383.9) |
| Overall mortality | 14.7% (145/986) |
| COVID-19 related mortality | 12.6% (124/986) |
| Mortality in fully vaccinated patients | 1% (2/204) |
| Median follow-up for CAR T-cell therapy cohort (months) | 68.3 (IQR 54.3–81.6) |
| Overall response rate at day +28 (CAR T therapy) | 70% |
| Complete response rate at day +28 (CAR T therapy) | 17% |
| Median duration of response (months) | 22.2 (95% CI 10.7–not reached) |
| MRD negativity at day +28 by flow cytometry | 70% (33/47) |
Key Findings
- COVID-19 mortality in allo-HCT patients decreased over time, with better survival in 2022 compared to 2020 and 2021.
- Risk factors for worse COVID-19 outcomes included older age, poor performance status, early post-transplant infection, ongoing immunosuppression, pre-existing lung disease, and recipient CMV seropositivity.
- Fully vaccinated allo-HCT patients had markedly lower COVID-19 mortality (1%).
- Children had significantly better COVID-19 outcomes than adults post-allo-HCT.
- In relapsed/refractory CLL treated with CD19 CAR T-cell therapy, 70% achieved MRD negativity at day +28, with a median duration of response exceeding 22 months.
- Concurrent ibrutinib and other patient/disease factors were analyzed for impact on CAR T-cell therapy outcomes in a 5-year follow-up.
Clinical Implications
Clinicians should recognize that despite improvements, allo-HCT recipients with certain risk factors remain vulnerable to severe COVID-19 and should prioritize vaccination and close monitoring. The durable responses observed with CD19 CAR T-cell therapy in R/R CLL support its use as a transformative treatment option, with MRD negativity serving as an important prognostic marker.
Conclusion
Outcomes for COVID-19 in allo-HCT patients have improved, yet high-risk groups require ongoing vigilance. Long-term follow-up of CD19 CAR T-cell therapy confirms sustained efficacy in R/R CLL, informing future therapeutic strategies.
References
- Ljungman et al. 2023 -- Improved Outcomes Over Time and Higher Mortality in CMV Seropositive Allogeneic Stem Cell Transplantation Patients with COVID-19: An IDWP Study from the EBMT Registry
- Liang et al. 2023 -- Factors Associated with Duration of Response After CD19 CAR T-Cell Therapy for Relapsed/Refractory CLL: 5-Year Follow-Up Update
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