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Responses to COVID-19 Vaccines Vary in Patients With Hematologic Malignancies

Patients with hematologic malignancies are known to be at risk of severe outcomes from COVID-19, and experts have recommended prioritizing these patients for COVID-19 vaccination.1,2

However, research has suggested that patients with hematologic malignancies may not mount an effective antibody response to vaccination.3

A study recently published in Cancer Cell provides insight into which hematologic malignancies and anticancer treatments confer a greater risk of poor antibody response, as well as which vaccine may be more likely to produce a response in patients with blood cancers.4

The prospective registry study ( Identifier: NCT04794387) included 1,445 evaluable patients with leukemia, lymphoma, or myeloma.

Researchers evaluated the anti-SARS-CoV-2 spike protein antibody response in these patients 14 days after they had received a second dose of an mRNA vaccine, either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna).

Differences in Response

The study revealed differences in antibody response by cancer type. Rates of seropositivity were higher in patients with Hodgkin lymphoma (98.5%), chronic myeloid leukemia (97.1%), acute myeloid leukemia (91.2%), T-cell lymphoma (84.6%), and acute lymphocytic leukemia (88.2%).

Likewise, 95.1% of patients with multiple myeloma showed at least some antibody response after vaccination, a higher rate than that reported in a previously published cohort.5

On the other hand, patients with B-cell non-Hodgkin lymphomas were less likely to have an antibody response. Rates of seronegativity were 55.6% in mantle cell lymphoma, 25.8% in Waldenstrom’s macroglobulinemia, 22.4% in follicular lymphoma, and 21.2% in diffuse large B-cell lymphoma patients.

Seronegativity was seen in 35.8% of patients with chronic lymphocytic leukemia, and 28% of these patients had not received any anticancer therapy in the past 2 years, a finding that is consistent with previously published results. 6,7

However, the study did show associations between anticancer therapies and antibody response. Anti-CD20 antibodies in particular were associated with a lack of response. For example, 56% of patients treated with rituximab were seronegative, as were 81.9% of patients who received obinutuzumab.

Patients who received BTK inhibitors also tended to have low or negative antibody levels. Seronegativity was observed in 51.4% of patients who received ibrutinib, 50% of those who received zanubrutinib, and 57.1% of those who received acalabrutinib.

Six of 7 patients treated with chimeric antigen receptor T cells targeting CD19 had no detectable antibodies.

“For patients who are on any kind of treatment that disables B lymphocytes, there is a problem in terms of mounting antibody response to COVID-19 vaccines or the virus itself,” explained Amit Verma, MBBS, director of the Division of Hemato-Oncology in the Montefiore Department of Oncology at Albert Einstein College of Medicine in New York, who was not involved in the study.

Dr Verma noted that these therapies “really blunt the ability of the body to produce an immunoglobulin response.”

Lastly, the study showed differences in antibody response by vaccine type. Multivariate analyses suggested that patients were significantly more likely to have an antibody response to the mRNA-1273 vaccine (Moderna) than to the BNT162b2 vaccine (Pfizer-BioNTech).

Implications of Antibody Test Results

“The antibody tests are emergency-authorized to detect antibody response to COVID-19 infection,” explained Lee Greenberger, PhD, chief scientific officer of the Leukemia and Lymphoma Society (LLS) and first author of the Cancer Cell study.

“We can also use them as a diagnostic as a tool to examine the response to vaccines while reporting back to patients, but we recognize that the implications of an antibody response to vaccines remain questionable.”

Some evidence has emerged that T cells can effectively mount an immune response to SARS-CoV-2 in hematologic cancer patients even without significant generation of antibodies,8 but it is currently unclear as to whether the same T-cell response will be seen after COVID-19 vaccination.

“[W]e don’t exactly know whether T cells are enough to mount an immune response and how effective these responses will be,” Dr Verma said.

The LLS is conducting a study9 to evaluate this as part of its National Patient Registry, which provided the cohort for the Cancer Cell study.

“T-cell response analysis is much harder to do than with antibodies, and the data is just beginning to emerge,” Dr Greenberger said. “There are many questions still to be answered: how much antibody/how much T-cell response do you need to offer protection from a COVID-19 infection? We still don’t know.”

In the meantime, patients who have low or undetectable antibody levels after vaccination should “take this as a warning” that they might be vulnerable to COVID-19 and speak to their physicians about it, Dr Greenberger said.

“What the physicians are likely to do is tell patients to wear your mask, get everybody vaccinated around you, observe the CDC guidelines,” Dr Greenberger said.

He also noted that, in some circumstances, vulnerable patients who have a known exposure to someone with COVID-19 might be considered for prophylactic treatment with monoclonal antibodies.

Potential of Booster Shots

In response to an increasing number of COVID-19 cases, the US Food and Drug Administration (FDA) recently authorized booster shots of COVID-19 vaccines for use in immunocompromised patients.10

It isn’t clear if patients with hematologic malignancies will benefit from a third vaccine dose. However, Dr Greenberger noted that some solid organ transplant recipients with low or no antibody titers after a second vaccine dose had an increase in antibodies after a third dose.11

“So we know it is possible,” Dr Greenberger said.

A case report of a lymphoma patient who had a response after a booster dose despite having received rituximab and BTK inhibitors also suggests that boosters could be beneficial for some patients.12

Dr Verma and colleagues are conducting a trial to assess the efficacy and safety of COVID-19 booster shots in patients with cancer.

“We just started a trial to evaluate the efficacy of a booster dose of Pfizer in patients with cancer who have been unable to mount an antibody response after initial vaccination,” Dr Verma said. “It won’t help everybody, but even if a third of patients do get benefit from a booster dose, I think we will make a difference.”

Disclosures: Dr Greenberger owns stocks in Bristol Myers Squibb and was previously employed by the company. Dr Verma declared affiliations with GlaxoSmithKline, Bristol Myers Squibb, Janssen, Incyte, MedPacto, Celgene, Novartis, Curis, Prelude, Eli Lilly and Company, Stelexis Therapeutics, Acceleron Pharma, and Throws Exception.


  1. Wood WA, Neuberg DS, Thompson JC, et al. Outcomes of patients with hematologic malignancies and COVID-19: A report from the ASH Research Collaborative Data Hub. Blood Adv. 2020; 4(23): 5966–5975. doi:10.1182/bloodadvances.2020003170
  2. Ribas A, Sengupta R, Locke T, et al. Priority COVID-19 vaccination for patients with cancer while vaccine supply is limited. Cancer Discov. 2021;11(2):233-236. doi:10.1158/2159-8290.CD-20-1817
  3. Thakkar A, Gonzalez-Lugo JD, Goradia N, et al. Seroconversion rates following COVID-19 vaccination among patients with cancer. Cancer Cell. 39(8):1081-1090.e2. doi:10.1016/j.ccell.2021.06.002
  4. Greenberger LM, Saltzman LA, Senefeld JW, et al. Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies. Cancer Cell. 2021;39(8):1031-1033. doi:10.1016/j.ccell.2021.07.012
  5. Pimpinelli F, Marchesi F, Piaggio G, et al. Fifth-week immunogenicity and safety of anti-SARS-CoV-2 Bnt162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: Preliminary data from a single institution. J Hematol Oncol. 2021;14(1):81. doi:10.1186/s13045-021-01090-6
  6. Parry H, McIlroy G, Bruton R, et al. Antibody responses after first and second COVID-19 vaccination in patients with chronic lymphocytic leukaemia. Blood Cancer J. 2021;11(7):136. doi:10.1038/s41408-021-00528-x
  7. Herishanu Y, Avivi I, Aharon A, et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood. 2021;137(23):3165-3173. doi:10.1182/blood.2021011568
  8. Bange EM, Han NA, Wileyto P, et al. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat Med. 2021;27(7):1280-1289. doi:10.1038/s41591-021-01386-7
  9. LLS urges blood cancer patients to get vaccinated as its national patient registry enters next phase in COVID-19 vaccine studies. Leukemia & Lymphoma Society. Published July 15, 2021.
  10. Coronavirus (COVID-19) Update: FDA authorizes additional vaccine dose for certain immunocompromised individuals. US Food and Drug Administration. Published August 12, 2021.
  11. Werbel WA, Boyarsky BJ, Ou MT, et al. Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: A case series. Ann Intern Med. Published June 15, 2021. doi:10.7326/L21-0282
  12. Hill JA, Ujjani CS, Greninger AL, Shadman M, Gopal AK. Immunogenicity of a heterologous COVID-19 vaccine after failed vaccination in a lymphoma patient. Cancer Cell. 2021;39(8):1037-1038. doi:10.1016/j.ccell.2021.06.015

This article originally appeared on Cancer Therapy Advisor

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