ABSTRACT
Introduction: Oncologists face challenges in the management of SARSCoV- 2 infections and post-SARS-CoV-2 cancer treatment. Accordingly, knowledge of their possible scenarios is of great importance. Methods: We analyzed diagnostic, clinical and post-SARS-CoV-2 scenarios in patients with RT-PCR confirmed SARS-CoV-2 infection presenting in the University Hospital of Gottingen, the University Hospital of Munster, and the Franziskus-Hospital Harderberg, Georgsmarienhutte, Germany. Results: Sixty-three patients with SARS-CoV-2 and hematologic or solid neoplasms were included. Thirty patients were initially asymptomatic, of whom ten developed COVID-19 symptoms (Figure 1A). Altogether 20 (32%) patients were asymptomatic, 18 (29%) had a mild, 12 (19%) a severe, and 13 (20%) a critical course (Figure 1B). Asymptomatic course was not associated with age, remission status, therapies or co-morbidities (p>0.3). Lymphocytopenia increased risk of severe/critical COVID-19 three-fold (p=0.015). Secondary bacterial infection accompanied more than one third of critical COVID-19 cases. 17 patients had died from COVID-19 (n=8) or PD (n=9) giving an estimated 73% four-month overall survival rate (Figure 2A-B). Post-SARSCoV- 2, treatment was delayed in 46 patients, of whom 9 developed progressive disease (PD). Cancer therapy was modified in 8 SARS-CoV-2 survivors because of deteriorating performance status or PD (Figure 2C). Conclusion: SARS-CoV-2 infection has a heterogenous course in cancer patients. Lymphocytopenia carries a significant risk of severe/critical COVID-19. SARS-CoV-2 disruption of therapy is serious as SARS-CoV-2 infection itself. Careful surveillance will allow early restart of the anti-cancer treatment.
ABSTRACT
Introduction: Immunosuppressed patients are at risk of a severe SARS-CoV-2 course. Patients after CAR-T-cell therapy inevitably have B-cell aplasia and are particularly vulnerable. Data on efficacy and optimal sequence of SARS-CoV-2 vaccination in CAR-T-cell recipients are missing. Methods: We analyzed all consecutive alive patients (predominantly DLBCL) undergoing CAR-T-cell therapy between 01/2019-08/2021. Patients received two Covid-19 mRNA vaccines between 01/2021-08/2021. We assessed the efficacy of the vaccines using IgG antibodies against SARS-CoV-2 spike protein (anti-S1/S2) (Clia Diasorin;cut-off >12 AU/ml) and separated patients into two groups: 1) CAR-T-cell infusion pre-vaccination;2) CAR-T cell infusion post-vaccination. Results: We identified 44 patients vaccinated with mRNA-1273 (Moderna) (33 pts;75%) or BNT162b2 (Pfizer-BioNTech) (11 pts;25%). In group 1 (28 pts), only 21% had positive antibodies after two vaccine doses while in group 2 (16 pts), 31% did so. In group 1, higher B-cell numbers (>22/μ l B-cells;PPV 83,3%;NPV 100%) and lower CAR-T-cell copy numbers (<50/μ g DNA CAR-T-cell copies;PPV 57.1%, NPV 94.4%) were predictive of positive humoral vaccine response. Patients without detectable B-cells when vaccinated produced negative antibody tests. In group 2, positive anti-spike protein IgG-antibodies after CAR-T-cell therapy declined by a median of 73.8 AU/ml at two consecutive assessments after a median of 74 days. Conclusion: Our results suggest poor humoral antibody responses in patients with prior CAR-T-cell therapy after mRNA Covid-19 vaccines. Low B-cell counts are associated with high CAR-T-cell copy numbers at vaccination and lacking antibody response. Anti-spike protein IgG values significantly declined in patients vaccinated before CAR-T-cell therapy.