AIMS: To evaluate antibody response to mRNA vaccine, identify subgroups with poor response and to determine long-term antibody durability in hematological patients. MATERIALS AND METHODS: We have vaccinated 292 patients with all hematological malignancies with a third dose of mRNA COMIRNATY vaccine with a 12-month follow-up period in our center in Ostrava, Czech Republic. RESULTS: Antibody response for the whole cohort exceeded 74% through the whole 12-month follow-up. Lowest seroconversion was observed in CLL cohort (20/41, 48.8%), patients who received anti-CD20 therapy < 6 months before vaccination (8/30, 26.7%) and BTK inhibitors (3/6, 50.0%). On the contrary, patients with chronic myeloproliferative neoplasms and acute leukemia performed comparably with healthy population (33/33; 100% and 12/13; 92.3%, respectively). We have seen better results if the time interval between anti-CD20 therapy and additional vaccine dose was longer than 6 months (5/8 patients achieved seroconversion on 4th booster dose after previous failure). Also, 36 patients received a 4th dose of vaccine as a booster with measurable increase in protective antibodies in 50% (18/36). CONCLUSIONS: Additional doses show promise for a well-timed revaccination even in poor responders. To our knowledge, no study comparable to our work in terms of follow-up length, vaccine consistency or variety of hematological malignancies and/or treatment has been reported yet. Our findings shed more light on long-term antibody response to mRNA vaccines against SARS-CoV-2 in patients with hematological cancer and bring important data for the evaluation of possible vaccine failure and scheduling of subsequent doses.

Department of Biomedical Informatics Faculty of Biomedical Engineering Czech Technical University Prague Prague Czech Republic

Department of Haemato Oncology University Hospital Ostrava Ostrava Czech Republic

Department of Haematology and Blood Transfusion Silesian Hospital in Opava Opava Czech Republic

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Zobrazit více v PubMed

Naimi A., Yashmi I., Jebeleh R., et al., “Comorbidities and Mortality Rate in COVID‐19 Patients With Hematological Malignancies: A Systematic Review and Meta‐Analysis,” Journal of Clinical Laboratory Analysis 36, no. 5 (2022): e24387, 10.1002/jcla.24387. PubMed DOI PMC

Della Pia A., Kim G. Y., Ip A., et al., “Anti‐Spike Antibody Response to the COVID Vaccine in Lymphoma Patients. Huber VC, Ed,” PLoS One 17, no. 12 (2022): e0266584, 10.1371/journal.pone.0266584. PubMed DOI PMC

Goel S., Gu J. J., Torka P., et al., “Determinants of COVID‐19 Vaccine Response in Patients With Lymphoma on B Cell Directed Therapy,” Blood 138, no. Supplement 1 (2021): 1340, 10.1182/blood-2021-152738. DOI

Branagan A. R., Lei M. M., Maron J. S., et al., “COVID‐19 Vaccine Responsiveness in Patients With Multiple Myeloma and Waldenström Macroglobulinemia,” Blood 138, no. 1 (2021): 3801, 10.1182/blood-2021-154089. DOI

Terao T., Yamashita T., Fukumoto A., et al., “Low Clinical Protective Response to SARS‐CoV‐2 mRNA COVID‐19 Vaccine in Patients With Multiple Myeloma,” International Journal of Hematology 115, no. 5 (2022): 737–747, 10.1007/s12185-022-03300-4. PubMed DOI PMC

Helfgott D. C., Racine‐Brzostek S., Short K. J., et al., “Immunogenicity of COVID‐19 mRNA Vaccines in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome,” Leukemia & Lymphoma 64, no. 3 (2023): 662–670, 10.1080/10428194.2022.2131414. PubMed DOI

Benjamini O., Rokach L., Itchaki G., et al., “Safety and Efficacy of the BNT162b mRNA COVID‐19 Vaccine in Patients With Chronic Lymphocytic Leukemia,” Haematologica 107, no. 3 (2021): 625–634, 10.3324/haematol.2021.279196. PubMed DOI PMC

Blumenthal K. G., Phadke N. A., and Bates D. W., “Safety Surveillance of COVID‐19 mRNA Vaccines Through the Vaccine Safety Datalink,” Journal of the American Medical Association 326, no. 14 (2021): 1375, 10.1001/jama.2021.14808. PubMed DOI

Terpos E., Rosati M., Bear J., et al., “Antibody Response to COVID‐19 mRNA Vaccine in Patients With Multiple Myeloma and Waldenstrom's Macroglobulinemia After Primary Immunization and Booster: Reactivity to the Sars‐Cov‐2 WT Virus, Delta and Omicron Variants,” Blood 140, no. 1 (2022): 4334–4335, 10.1182/blood-2022-163521. DOI

Mehta‐Shah N., Bartlett N. L., Kahl B., et al., “COVID‐19 Booster Vaccines Generate Seroconversion in Subset of Patients With Lymphoma/CLL: Single Institution Experience,” Leukemia & Lymphoma 63, no. 7 (2022): 1723–1727, 10.1080/10428194.2022.2038377. PubMed DOI

Šušol O., Šušolová B., and Hájek R., “Effect of a Third Booster Dose of COVID‐19 mRNA Vaccine in Patients With Haematological Cancer After the Initial Two‐Dose Vaccination—A Single Centre Report,” Journal of Vaccines and Immunology 8, no. 1 (2022): 29–32, 10.17352/jvi.000052. DOI

Šušol O., Hájková B., Jelínek T., et al., “Immune Response in 465 Hematological Patients Vaccinated with mRNA Vaccine Against SARS‐CoV‐2: A Single Centre Experience,” SSRN (2021), 10.2139/ssrn.3960655. DOI

Freifeld A. G., Bow E. J., Sepkowitz K. A., et al., “Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients With Cancer: 2010 Update by the Infectious Diseases Society of America,” Clinical Infectious Diseases 52, no. 4 (2011): e56–e93, 10.1093/cid/cir073. PubMed DOI

Storek J., Dawson M. A., Lim L. C. L., et al., “Efficacy of Donor Vaccination Before Hematopoietic Cell Transplantation and Recipient Vaccination Both Before and Early After Transplantation,” Bone Marrow Transplantation 33, no. 3 (2004): 337–346, 10.1038/sj.bmt.1704336. PubMed DOI

Tomblyn M., Chiller T., Einsele H., et al., “Guidelines for Preventing Infectious Complications Among Hematopoietic Cell Transplantation Recipients: A Global Perspective,” Biology of Blood and Marrow Transplantation 15, no. 10 (2009): 1143–1238, 10.1016/j.bbmt.2009.06.019. PubMed DOI PMC

Ljungman P., Engelhard D., de la Camara R., et al., “Vaccination of Stem Cell Transplant Recipients: Recommendations of the Infectious Diseases Working Party of the EBMT,” Bone Marrow Transplantation 35, no. 8 (2005): 737–746, 10.1038/sj.bmt.1704870. PubMed DOI

Rubin L. G., Levin M. J., Ljungman P., et al., “2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host,” Clinical Infectious Diseases 58, no. 3 (2014): e44–e100, 10.1093/cid/cit684. PubMed DOI

Šimánek V., Pecen L., Krátká Z., et al., “Five Commercial Immunoassays for SARS‐CoV‐2 Antibody Determination and Their Comparison and Correlation With the Virus Neutralization Test,” Diagnostics 11, no. 4 (2021): 593, 10.3390/diagnostics11040593. PubMed DOI PMC

Wendel S., Kutner J. M., Machado R., et al., “Screening for sars‐cov‐2 Antibodies in Convalescent Plasma in Brazil: Preliminary Lessons From a Voluntary Convalescent Donor Program,” Transfusion (Paris) 60, no. 12 (2020): 2938–2951, 10.1111/trf.16065. PubMed DOI PMC

Lee W. T., Girardin R. C., Dupuis A. P., et al., “Neutralizing Antibody Responses in COVID‐19 Convalescent Sera,” Journal of Infectious Diseases 223, no. 1 (2021): 47–55, 10.1093/infdis/jiaa673. PubMed DOI PMC

Mai A. S., Lee A. R. Y. B., Tay R. Y. K., et al., “Booster Doses of COVID‐19 Vaccines for Patients With Haematological and Solid Cancer: A Systematic Review and Individual Patient Data Meta‐Analysis,” European Journal of Cancer 172 (2022): 65–75, 10.1016/j.ejca.2022.05.029. PubMed DOI PMC

Saade C., Gonzalez C., Bal A., et al., “Live Virus Neutralization Testing in Convalescent Patients and Subjects Vaccinated Against 19A, 20B, 20I/501Y.V1 and 20H/501Y.V2 Isolates of SARS‐CoV‐2,” Emerging Microbes & Infections 10, no. 1 (2021): 1499–1502, 10.1080/22221751.2021.1945423. PubMed DOI PMC

Shen Y., Freeman J. A., Holland J., et al., “Multiple COVID‐19 Vaccine Doses in CLL and MBL Improve Immune Responses With Progressive and High Seroconversion,” Blood 140, no. 25 (2022): 2709–2721, 10.1182/blood.2022017814. PubMed DOI PMC

Wirth S. R. M., Podar K., Pecherstorfer M., Wohlfarth P., Jaeger U., and Singer J., “Evaluation of Antibody Responses in Patients With B‐Cell Malignancies After Two and Three Doses of Anti‐SARS‐CoV‐2 S Vaccination—A Retrospective Cohort Study,” Cancers 15, no. 2 (2023): 524, 10.3390/cancers15020524. PubMed DOI PMC

Obeid M., Suffiotti M., Pellaton C., et al., “Humoral Responses Against Variants of Concern by COVID‐19 mRNA Vaccines in Immunocompromised Patients,” JAMA Oncology 8, no. 5 (2022): e220446, 10.1001/jamaoncol.2022.0446. PubMed DOI PMC

Cook L. B., O'Dell G., Vourvou E., et al., “Third Primary SARS‐CoV‐2 mRNA Vaccines Enhance Antibody Responses in Most Patients With Haematological Malignancies,” Nature Communications 13, no. 1 (2022): 6922, 10.1038/s41467-022-34657-z. PubMed DOI PMC

Piñana J. L., Vazquez L., Calabuig M., et al., “One‐Year Breakthrough SARS‐CoV‐2 Infection and Correlates of Protection in Fully Vaccinated Hematological Patients,” Blood Cancer Journal 13, no. 1 (2023): 8, 10.1038/s41408-022-00778-3. PubMed DOI PMC

Perry C., Luttwak E., Balaban R., et al., “Efficacy of the BNT162b2 mRNA COVID‐19 Vaccine in Patients With B‐Cell Non‐Hodgkin Lymphoma,” Blood Advances 5, no. 16 (2021): 3053–3061, 10.1182/bloodadvances.2021005094. PubMed DOI PMC

Lim Y. J., Ward V., Brown A., et al., “Immunogenicity of covid ‐19 Vaccines in Patients With Follicular Lymphoma Receiving Frontline Chemoimmunotherapy,” British Journal of Haematology 205, no. 2 (2024): 440–451, 10.1111/bjh.19562. PubMed DOI

Rotterdam J., Thiaucourt M., Weiss C., et al., “Definition of Factors Associated With Negative Antibody Response After COVID‐19 Vaccination in Patients With Hematological Diseases,” Annals of Hematology 101, no. 8 (2022): 1825–1834, 10.1007/s00277-022-04866-z. PubMed DOI PMC

Saito M., Mori A., Ishio T., et al., “Initial Efficacy of the COVID‐19 mRNA Vaccine Booster and Subsequent Breakthrough Omicron Variant Infection in Patients With B‐Cell Non‐Hodgkin's Lymphoma: A Single‐Center Cohort Study,” Viruses 16, no. 3 (2024): 328, 10.3390/v16030328. PubMed DOI PMC

Avivi I., Luttwak E., Saiag E., et al., “BNT162b2 mRNA COVID‐19 Vaccine Booster Induces Seroconversion in Patients With B‐Cell Non‐Hodgkin Lymphoma Who Failed to Respond to Two Prior Vaccine Doses,” British Journal of Haematology 196, no. 6 (2022): 1329–1333, 10.1111/bjh.18029. PubMed DOI

Mancuso K., Zamagni E., Solli V., et al., “Long Term Follow‐Up of Humoral and Cellular Response to mRNA‐Based Vaccines for SARS‐CoV‐2 in Patients With Active Multiple Myeloma,” Frontiers in Oncology 13 (2023): 1208741, 10.3389/fonc.2023.1208741. PubMed DOI PMC

Goldwater M. S., Stampfer S. D., Sean Regidor B., et al., “Third Dose of an mRNA COVID‐19 Vaccine for Patients With Multiple Myeloma,” Clinical Infection in Practice 17 (2023): 100214, 10.1016/j.clinpr.2022.100214. PubMed DOI PMC

Tartof S. Y., Slezak J. M., Puzniak L., et al., “Effectiveness of a Third Dose of BNT162b2 mRNA COVID‐19 Vaccine in a Large US Health System: A Retrospective Cohort Study,” Lancet Regional Health–Americas 9 (2022): 100198, 10.1016/j.lana.2022.100198. PubMed DOI PMC

Jamous Y. F. and Alhomoud D. A., “The Safety and Effectiveness of mRNA Vaccines Against SARS‐CoV‐2,” Cureus 20 (2023): e45602, 10.7759/cureus.45602. PubMed DOI PMC

Martínek J., Tomášková H., Janošek J., et al., “Immune Response 5–7 Months After Vaccination Against SARS‐CoV‐2 in Elderly Nursing Home Residents in The Czech Republic: Comparison of Three Vaccines,” Viruses 14, no. 5 (2022): 1086, 10.3390/v14051086. PubMed DOI PMC

Claudiani S., Apperley J. F., Parker E. L., et al., “Durable Humoral Responses After the Second Anti‐SARS‐CoV‐2 Vaccine Dose in Chronic Myeloid Leukaemia Patients on Tyrosine Kinase Inhibitors,” British Journal of Haematology 197, no. 1 (2022): e1–e4, 10.1111/bjh.18001. PubMed DOI

Mori A., Onozawa M., Kobayashi M., et al., “Booster Effect of a Third mrna ‐Based covid ‐19 Vaccine Dose in Patients With Myeloid Malignancies,” Cancer Medicine 12, no. 16 (2023): 16881–16888, 10.1002/cam4.6314. PubMed DOI PMC

Mellinghoff S. C. and Cornely O. A., “SARS‐CoV‐2 Vaccination in CLL: How Often Is Enough?,” Blood 140, no. 25 (2022): 2655–2657, 10.1182/blood.2022018586. PubMed DOI PMC

Braitsch K., Jeske S. D., Stroh J., et al., “Tixagevimab/Cilgavimab for COVID‐19 Pre‐Exposure Prophylaxis in Hematologic Patients—A Tailored Approach Based on SARS‐CoV‐2 Vaccine Response,” Vaccine 12, no. 8 (2024): 871, 10.3390/vaccines12080871. PubMed DOI PMC