There is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin’s lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT50) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT50 levels, with 50-60% of them below the detection limit; (3) mean NT50 levels in patients with CLL and NHL was ~2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT50 levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.

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Background: Our group previously reported a 16% incidence of HC after hematopoietic cell transplantation (HCT) involving mostly matched unrelated donors (85%) and ATG-containing regimens (80%) (Silva, Haematologica 2010). PT-Cy is an effective GVHD prophylaxis in haplo-or matched unrelated transplants. There is a paucity of information about the risk of HC in this setting. Objective: To retrospectively assess the incidence and clinical factors associated with HC in alloHCT recipients receiving PTCy as GVHD prophylaxis. Methods: A retrospective analysis of patients (pts.) who underwent HCT with PT-Cy at our center between 2012-2018 was performed. We stratified the study cohort (N=478) into HC (N=193, 40%) and Non-HC (N=285, 60%) to compare their characteristics and outcome. Association between HC and clinical variables was assessed using logistic regression modeling. Results: Pt's age, HCT-CI, # prior therapies, disease type and status were not statistically different between the 2 groups. However, the HC group pts. were more likely to have received more intense conditioning (Busulfan/Fludarabine(BF) +/-Clofarabine, or Thio; F/Melphalan (FM) 140+/-Thio or TBI vs. FM 100+/-TBI) (p=0.018), had haplo-transplants (p=0.018), BM as graft (p=0.021), and tacrolimus+mycophenolate mofetil (MMF) (p=0.043). Delayed ANC engraftment (p=0.032) and time to achieve an absolute lymphocyte count >500 was noted in HC group (p=0.014). 54% of HC pts. had grade 2-4 cystitis and BK virus was isolated in 87% of cases. CMV viremia was higher in HC group compared to Non-HC group (p<0.001). HC pts. experienced a higher # of hospitalizations (p=0.012) and longer hospital stay (p=0.06) days compared to Non-HC pts. Additionally, HC pts. were more likely to experience grade II-IV aGVHD compared to Non-HC pts (p=0.005). In multivariable analysis, conditioning intensity remained significant [HR 2.27 (95% CI: 1.28, 4.01); p=0.005]. Conclusion: Our study showed a 40% incidence of HC after HCT recipients receiving PT-Cy. The intensity of the conditioning regimen is an independent predictive factor for developing HC. A formal comparison to ATG-containing regimens is in progress.

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