COVID Vaccine Shortfalls in Blood Cancer Patients

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On June 11, 2021, MedPage Today reported on a study in Cancer Cell showing that while patients with cancer who were vaccinated against COVID-19 achieved high seroconversion rates, those rates were significantly lower among patients with hematologic malignancies, and particularly so for those who had undergone highly immunosuppressive therapies.

Here, as part of our review of the year’s top stories, we assess subsequent studies showing that patients with blood cancers remain at risk of serious outcomes from COVID-19, even if fully vaccinated, and how there is a clear benefit to giving those patients a third dose of an mRNA vaccine in order to induce or boost immune response.

While patients with cancer have been considered a priority group for SARS-CoV-2 vaccination, it has become evident that patients with blood cancers are less likely to develop an immune response than those with solid tumors.

In a systematic review and meta-analysis of 23 studies involving cancer patients, researchers found that when analyzing serological response after complete immunization regimens, patients with blood cancers had a significantly reduced humoral response (65%, 95% CI 57%-72%) than seen among those with solid cancer (94%, 95% CI 86%-97%).

An example of one of the many studies looking at the question of hematologic disease and response to COVID vaccination was presented at this year’s annual meeting of the American Society of Hematology (ASH). Susanne Saussele, MD, of Universität Heidelberg in Germany, presented a study showing that about 15% of patients with blood disorders had no vaccination-related antibodies after receiving a COVID-19 vaccine, with lymphoma patients and those currently receiving treatment much less likely to build antibodies.

The death of former Secretary of State Colin Powell in October after a COVID-19 infection served as a further reminder of the risk COVID-19 presents to patients with blood cancers. Although fully vaccinated, the 84-year-old Powell had been treated for multiple myeloma and thus not only had an immune system weakened by his age, but one that was probably weakened by his disease and associated treatments.

“Colin Powell’s death due to complications of COVID-19 is a real-life example of the elevated risk blood cancer patients face,” said Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, in a statement. “I urge all blood cancer patients and survivors to get vaccinated — including with a third dose, unless told otherwise by their doctor.”

Growing concerns about the immunocompromised and elderly led the CDC in August to recommend that people with moderately and severely compromised immune systems who have received an initial mRNA two-dose vaccine series get a third dose at least 4 weeks after their second shot.

The American Society of Hematology followed up with recommendations on which people are candidates for a third mRNA vaccine dose. These included patients:

  • Under active treatment for hematologic malignancy
  • Treated in the prior 12 months with an agent that causes prolonged B-cell aplasia or lymphopenia
  • With chronic lymphocytic leukemia, regardless of treatment
  • CAR T-cell recipients (within 2 years)
  • Hematopoietic stem cell transplant recipients (within 2 years)

Although evidence regarding the efficacy of a third vaccine dose is limited at this point, it appears a COVID-19 booster significantly increases the immune response in many hematological patients.

In November, the same group that published that initial study in Cancer Cell in June reported on the efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccination in cancer patients.

Of 88 patients in the study who received booster vaccinations, 56 (64%) were seropositive prior to a third dose, while 32 (36%) were seronegative. All, save one, had hematological malignancies.

The investigators found that of those 32 seronegative patients, 18 (56%) seroconverted anti-S IgG titers after booster vaccination.

These findings call “for broad efforts to provide third vaccinations to such patients,” wrote Balazs Halmos, MD, MS, of Montefiore Einstein Cancer Center in New York City, and colleagues in Cancer Cell.

And in a study presented at ASH, Lee Greenberger, PhD, of the Leukemia & Lymphoma Society, reported on 24 patients in the organization’s national registry who had received a third shot after full vaccination with mRNA vaccines.

Twenty of those 24 patients had been seronegative more than 14 days after receiving their second vaccination, while the remaining four had low seropositivity.

Eleven had chronic lymphocytic leukemia, seven non-Hodgkin’s lymphoma, five Waldenström macroglobulinemia, and one multiple myeloma. They received booster vaccinations 21 to 114 days after completing the initial vaccination series between January and April 2021.

Greenberger and his colleagues found that the four patients who had a low level of antibody response to the initial vaccination series had a augmented antibody response with the booster. In addition they reported:

  • Two of eight patients who received anti-CD20 antibody treatment in the 6 months prior to vaccination seroconverted after booster vaccination.
  • Two out of three seronegative patients receiving anti-CD20 therapy in the last 2 years (but >6 months) seroconverted after the booster.
  • One patient with follicular lymphoma who received anti-CD20 therapy in 2019 remained seronegative despite a prolonged duration without therapy.
  • Of the six seronegative patients taking BTK inhibitors, three seroconverted after the booster.
  • Two of the three remaining seronegative patients were taking concomitant anti-CD20 therapy.
  • Of the four seronegative patients not currently taking anti-B-cell therapy, three seroconverted and one on IV immunoglobulin remained seronegative.
  • A patient currently receiving chemotherapy also did not respond to a booster.

“Our data shows a clear benefit of giving blood cancer patients three primary vaccine doses, but there is still a large portion of patients who will remain at risk even with the additional dose,” Greenberger said in a statement.

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

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