ABSTRACT
Background and Aims: SARS-CoV-2 mRNA vaccines have been approved to prevent COVID-19. We assessed immunogenicity, effectiveness and safety of vaccines in patients with compensated and decompesated cirrhosis. Method: This is a prospective single center study assessing humoral and cellular responses in cirrhotics compared to healthy controls, incidence post-vaccination SARS-CoV-2 infections and adverse events (AEs). Antibodies against the spike- and nucleocapside-protein (anti-S and anti-N) were tested at baseline, 21 days after the first and second doses and during follow-up. Spike-specific T-cells quantity assessment was longitudinally conducted by the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by IFN-γ and IL-2 measurement. Results: 182 cirrhotics (61 years, 75% males, 45% viral-related, 74% Child-Pugh A, 31% HCC, 85% COVID-19 naïve) and 38 healthy subjects were enrolled. Previous SARS-CoV-2 infection predicted higher anti-S titres at all time points after vaccination, in both groups. COVID-19 naïve cirrhotics showed significantly lower anti-S titres compared to controls [998.5 (0.4-12,500) vs 1,520 (259-12,500) U/mL, p=0.048], anti-S titres significantly decreased after a median of 133 (70-182) days [536 (0.4-8,777) U/mL, p<0.0001] and were lower in decompensated vs compensated cirrhosis [632 (0.4-12,500) vs 1,377 (0.4-12,500) U/mL, p=0.028]. By multivariable analysis in COVID-19 naïve cirrhotics, independent predictors of lower anti-S were active HCC, immunocompromised conditions, BNT162b2 and lower anti-S after first dose. The spike-specific T-cell response was evaluated in 14 cirrhotics, showing a heterogeneous magnitude of response, but on average the quantity and kinetics of decline of the spike-specific cellular responses diverged in cirrhotics compared to controls, with lower concentrations of both IFN-γ and IL-2. During follow-up, 4/133 (3%) COVID-19 naïve cirrhotics tested positive for anti-N, all asymptomatic. Neither unexpected nor severe AEs emerged. Conclusion: Humoral and cellular responses to SARS-CoV-2 mRNA vaccines appeared suboptimal in patients with cirrhosis, however the rate of post-vaccination infection seems low.
ABSTRACT
Introduction: Patients (pts) with aggressive B-cell lymphoma and MYC rearrangement exhibits poor outcome after R-CHOP treatment. In the last decade, these pts were treated with a new dose-dense, short-term therapy termed “CARMEN”, at several Italian Centers. Excellent efficacy and safety profile have been reported in HIV/AIDS pts with high-risk Burkitt lymphoma (BL) [Ferreri et al. BJH 2021], but its efficacy in pts with high-grade B-cell lymphoma with MYC rearrangement (HGBCL) remains to be defined. Herein, we report a retrospective series of consecutive pts with BL or HGBCL treated with CARMEN regimen. Methods: Either HIV-negative and HIV-positive pts aged 18-80 years with BL or HGBCL and MYC rearrangement positive by FISH were treated with CARMEN regimen, which includes a single 36-day induction course of sequential doses of cyclophosphamide, vincristine, rituximab, methotrexate, VP16, and doxorubicin plus intrathecal chemotherapy, followed by consolidation with HD-cytarabine ± cisplatin. Pts who did not achieve complete remission (CR) after induction received BEAM/ASCT after consolidation. Results: 63 pts (22 HGBCL;41 BL) received the CARMEN regimen (Table). Treatment was well tolerated: 56 (89%) pts completed the induction, and 55 (87%) completed the consolidation. G4 hematological toxicity during induction was neutropenia in 48 (76%) pts, thrombocytopenia in 24 (38%) and anemia in 7 (11%), which were recorded after consolidation in 34 (62%), 38 (69%) and 1 (2%) pt, respectively. G4 non hematological toxicity was uncommon: mucositis in 4 (6%) pts and tumor lysis syndrome in 1 (2%) during induction, and heart failure and bleeding in 1 (2%) pt each after consolidation. G4 infections were recorded in 4 (6%) pts during induction and in 2 (3%) after consolidation. Induction and consolidation doses were reduced in 6 (9%) and 4 (7%) pts, respectively. Seven HGBCL and 9 BL pts received ASCT, with expected tolerability. 4 HGBCL and 2 BL pts died of toxicity (sepsis in 4;respiratory failure;COVID-19), with a TRM of 9%. After induction, 18 (82%) HGBCL and 37 (90%) BL pts achieved a response, which was CR in 10 (45%) and 26 (63%) pts, respectively. After the whole treatment, 15 (68%) HGBCL pts and 32 (78%) BL pts achieved a CR, and, at a median follow-up of 54 (2-131) months, 15 (100%) HGBCL and 29 (91%) BL pts remain relapse-free, with a 5-yr PFS of 67% and 70%, respectively. 15 HGBCL and 32 BL pts are alive, with a 5-yr OS of 66% and 77%, respectively. HIV seropositivity did not modify outcome. Age and LDH level were independently associated with OS. Conclusions: With the limitations of a retrospective series, this study shows that CARMEN is a safe and active treatment both in HIVnegative and-positive pts with HGBCL and MYC rearrangement and BL. Survival figures in HGBCL pts compare favorably with results reported with R-CHOP or analogous, and are similar to those achieved in BL pts.