Clinical Scorecard: Highlights from the 49th Annual Conference of the European Society for Blood and Marrow Transplantation: Recognizing Award-Winning Physicians (O001-O008)

At a Glance

Key Highlights

• Mortality in allo-HCT patients with COVID-19 has decreased over time, with improved outcomes noted in 2022 compared to 2020 and 2021.
• Risk factors for worse COVID-19 outcomes in allo-HCT patients include older age, poor performance status, early post-transplant infection, ongoing immunosuppression, pre-existing lung disease, and recipient CMV seropositivity.
• In a phase I/II trial of CD19 CAR T-cell therapy for R/R CLL, a 70% overall response rate was observed with a median duration of response of 22.2 months and 70% achieving MRD-negativity at day +28.

Guideline-Based Recommendations

Diagnosis

• Include PCR or antigen testing for SARS-CoV-2 in allo-HCT recipients regardless of symptoms.
• Assess measurable residual disease (MRD) by multiparameter flow cytometry and next-generation sequencing in CLL patients post-CAR T-cell therapy.

Management

• Vaccination is critical; fully vaccinated allo-HCT patients had significantly lower COVID-19 mortality.
• Monitor and manage immunosuppression carefully in allo-HCT patients to reduce COVID-19 severity.
• Use defined-composition CD19 CAR T-cell therapy with or without concurrent ibrutinib for R/R CLL.

Monitoring & Follow-up

• Follow-up for at least six weeks post-COVID-19 diagnosis in allo-HCT patients to assess outcomes.
• Long-term follow-up (median 68 months) for CAR T-cell therapy patients to evaluate duration of response and MRD status.

Risks

• High mortality risk in allo-HCT patients contracting COVID-19 within 100 days post-transplant.
• Increased risk of severe COVID-19 with recipient CMV seropositivity and pre-existing lung disease.
• Potential relapse or progression in R/R CLL despite CAR T-cell therapy, necessitating ongoing monitoring.

Patient & Prescribing Data

986 allo-HCT patients with COVID-19; 49 patients with R/R CLL treated with CD19 CAR T-cell therapy

Only 1% mortality from COVID-19 in fully vaccinated allo-HCT patients; durable responses with median 22.2 months duration in CAR T-cell treated CLL patients with 70% MRD negativity at day +28.

Clinical Best Practices

• Prioritize COVID-19 vaccination in allo-HCT recipients to reduce mortality.
• Identify and closely monitor allo-HCT patients with risk factors such as early post-transplant infection, immunosuppression, and CMV seropositivity.
• Incorporate MRD assessment in evaluating response to CD19 CAR T-cell therapy in CLL.
• Consider concurrent ibrutinib with CAR T-cell therapy to potentially enhance outcomes.
• Maintain long-term follow-up for CAR T-cell therapy patients to monitor response durability and relapse.

References

• European Society for Blood and Marrow Transplantation Annual Meeting 2023
• Turtle et al., JCO 2017 - CD19 CAR T-cell therapy in CLL
• Gauthier et al., Blood 2019 - Concurrent ibrutinib with CAR T-cell therapy