Immunogenicity of Sars-Cov-2 mRNA 1273 Vaccine in Patients with Lymphoid Malignancies
Authors: Dong Ning , Jain Akriti G , Tan Elaine S , Ball Somedeb , Whiting Junmin , Gaballa Sameh , Isenalumhe Leidy , Bello Celeste , Saeed Hayder , Shah Bijal D. , Locke Frederick L. , Chavez Julio C. , Lancet Jeffrey E. , Sokol Lubomir , Pinilla Ibarz Javier , Giuliano Anna 
Published: November 2021

Abstract
Introduction:
Patients (pts) with hematological malignancies (HMs) are at increased risk for severe COVID19 infection and death (Grivas, 2021). Currently, vaccination represents the most effective prevention approach. HM pts have been shown to have lower immune responses to COVID19 vaccine, particularly those with lymphoid malignancies (LMs) (Herishanu, 2021; Thakkar 2021; Tzarfari 2021). We conducted an observational cohort study at Moffitt Cancer Center (MCC) to evaluate the immune response following one and two doses of the mRNA1273 (Moderna) vaccine in cancer pts. Here we report the results for pts with LMs and assessed associated factors.
Methods:
MCC pts who presented for the first mRNA-1273 vaccine dose from 1/12/2021-1/25/2021 and who provided consent were enrolled. Blood samples were collected prior to the 1 st and 2 nd doses (Days 1 and 29) and ~28 days after the 2 nd dose (Day 57). The IgG response against the SARS-CoV-2 spike (S) protein was measured using a two-step ELISA adapted from the Krammer (Icahn School of Medicine at Mount Sinai) protocol. The total 103 LM pts who received both vaccine doses and had samples at all time points were included in analyses. The 214 pts with solid tumors (ST) were included as comparison. Associations of seroconversion (SV) rates with pt characteristics were evaluated using the Fisher exact test or Chi-square test as appropriate. Associations of antibody (Ab) titers with pt characteristics were examined using Kruskal Wallis test. Factors independently associated with SV rates were evaluated using multivariable logistic regression. All analyses were performed using SAS 9.4 and R studio.
Results:
Baseline characteristics, cancer treatments and SV rates by these factors are listed in Tables 1 and 2. 55 pts had B-cell non-Hodgkin lymphoma (B-NHL), 23 had chronic lymphocytic leukemia (CLL), 15 had T- or NK-cell lymphoma (T/NK lymphoma) and 10 had Hodgkin lymphoma (HL).
SV rates were significantly lower for LM pts compared to ST pts (49.5% vs 86.9% after the 1st dose and 68.9% vs 98.1% after the 2 nd dose, respectively, p&lt;0.0001 for both doses). Pts with CLL and B-NHL had the lowest SV rates (21.7% and 43.6% after dose 1 and 65.2% and 58.2% after dose 2, respectively). None of the 11 pts on anti-CD20 monoclonal Ab (mAb) seroconverted after 2 doses. Pts on BTK inhibitors (BTKi) or PI3K inhibitors (PI3Ki) or venetoclax also had low SV rates [4/12 (33.3%) after 2 doses]. Only 1 out of the 8 pts post CAR-T seroconverted, despite the fact that 6 pts had CAR-T &gt;12 months ago and 6 pts were in remission and have not received any cancer treatment after CAR-T. Pts with CLL and B-NHL but not on CD20 mAb/BTKi/PI3Ki/venetoclax or post CAR-T had much higher SV rates (31.3-60.5% after dose 1 and 79.0-81.3% after dose 2, Table 3). Other factors associated with lack of SV after 2 doses included: lymphocyte &lt;1 x 10 9/L, low IgG level and on anticancer treatment within 3 months. Multivariate analyses showed that diagnosis of CLL or B-NHL compared to ST, CAR-T and CD20 mAb/BTKi/PI3Ki/venetoclax were independently associated with decreased SV after 2 doses (Table 4).
In the univariate model, Ab titers after 1 and 2 doses were significantly lower in pts with diagnosis of CLL/B-NHL, low lymphocyte count, low IgG and on cancer treatment (Figures 1-3). HL and T/NK lymphoma had titers comparable to solid tumors (Figure 1).
Conclusions:
Pts with CLL and B-NHL had low SV rates and Ab titers after receiving the mRNA-1273 vaccine when compared with ST, HL and T/NK-lymphoma. Current or past treatments with CD20 mAb/BTKi/PI3Ki/venetoclax and CAR-T were associated with lower immune response, with pooled SV rates of 16.7% after 2 doses. In general, LM pts had lower SV rates and Ab titers after the 1 st dose vs ST, but responses improved after the 2 nd dose. Further studies are needed to improve immune responses to COVID19 vaccines in LM pts, including the potential role of a 3 rd booster dose.
Figure 1 Figure 1.

Disclosures
Gaballa: Adaptive Biotechnologies: Research Funding; Epizyme: Consultancy, Research Funding; TG therapeutics: Consultancy, Speakers Bureau; Beigene: Consultancy; ADC Therapeutics: Consultancy. Saeed: Bristol-Myers Squibb Company: Consultancy; sano-aventis U.S.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutica Products, LP: Consultancy, Other: investigator; Celgene Corporation: Consultancy, Other: investigator; MEI Pharma Inc: Consultancy, Other: investigator; Kite Pharma: Consultancy, Other: investigator; Other-TG therapeutics: Consultancy, Other: investigator; Nektar Therapeutics: Consultancy, Other: research investigator; MorphoSys AG: Consultancy, Membership on an entity's Board of Directors or advisory committees; Other-Epizyme, Inc.: Consultancy; Other-Secura Bio, Inc.: Consultancy; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shah: Pharmacyclics/Janssen: Honoraria, Other: Expenses; Pfizer: Consultancy, Other: Expenses; BeiGene: Consultancy, Honoraria; Servier Genetics: Other; Jazz Pharmaceuticals: Research Funding; Precision Biosciences: Consultancy; Amgen: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Acrotech/Spectrum: Honoraria; Novartis: Consultancy, Other: Expenses; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy; Incyte: Research Funding. Locke: Janssen: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; EcoR1: Consultancy; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Calibr: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Umoja: Consultancy, Other; Cowen: Consultancy; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Legend Biotech: Consultancy, Other. Chavez: Abbvie: Consultancy; AstraZeneca: Research Funding; Kite/Gilead: Consultancy; Karyopharm Therapeutics: Consultancy; MorphoSys: Speakers Bureau; Epizyme: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Merck: Research Funding; Adaptive: Research Funding; BeiGene: Speakers Bureau; Novartis: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lancet: AbbVie: Consultancy; ElevateBio Management: Consultancy; Daiichi Sankyo: Consultancy; Celgene/BMS: Consultancy; Millenium Pharma/Takeda: Consultancy; BerGenBio: Consultancy; Agios: Consultancy; Astellas: Consultancy; Jazz: Consultancy. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Pinilla Ibarz: AbbVie, Janssen, AstraZeneca, Novartis, TG Therapeutics, Takeda: Consultancy, Other: Advisory; Sellas: Other: ), patents/royalties/other intellectual property; MEI, Sunesis: Research Funding; AbbVie, Janssen, AstraZeneca, Takeda: Speakers Bureau. Giuliano: Merck & CO: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.