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Immune Responses to COVID-19 Vaccines Low Among Patients with Hematologic Malignancies, but mRNA Vaccines Induce Strong Antibody Response in AML and MDS

JHOP - February 2022 Vol 12, No 1 - ASH Highlights
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Results of 2 single-center studies presented at the 2021 American Society of Hematology annual meeting showed that a significant number of patients with hematologic diseases have no, or low, immune response after receiving a second COVID-19 vaccine, especially in patients with lymphoid diseases; however, the mRNA-1273 SARS CoV-2 vaccine induces a strong antibody response in patients with acute myeloid leukemia (AML) or with myelodysplastic syndrome (MDS).

Prospective Study

In a prospective study in Germany, a negative vaccination-related antibody response was observed in 15% (N = 56) of 373 patients with hematologic diseases (median age, 64 years; 44% female), including 338 with hematologic malignancies. Of the 56 patients with negative vaccination response, 71% (N = 39) were receiving active cancer therapy and 29% (N = 17) had received previous therapy or were treatment-naïve.1

“Negative seroconversion occurred predominantly in lymphoid neoplasms,” said Jil Rotterdam, MD, Universität Heidelberg, Germany, who presented the results.

Of the 338 patients with hematologic malignancies, 67% had myeloid neoplasms and 33% had lymphoid neoplasms. The cohort of 35 vaccinated patients with nonmalignant hematologic diseases served as the controls.

More than 80% of the patients received 2 doses of mRNA vaccines. The time between vaccination and analysis was 12 weeks. Overall, 229 (61%) patients with hematologic cancer were receiving active therapy and 39% had received previous therapy or were treatment-naïve.

Positive seroconversion, defined as ≥0.8 U/mL antibody titer, was demonstrated for 85% of patients, with a mean titer value of 197 U/mL. Of the patients with a positive antibody titer, 89 (28%) had a response between 0.8 U/mL and 250 U/mL.

Negative seroconversion occurred predominantly in patients with lymphoid neoplasms. Of the 56 patients with no seroconversion, 40 (72%) had lymphoid neoplasms, which “reflects 36% of all patients with lymphoid diseases,” said Dr Rotterdam. In addition, 2 (21.4%) patients had myeloid neoplasms and 4 (7.1%) had autoimmune disease.

Of the 56 patients with no response to vaccination, 71% (N = 39) were receiving active therapy and 29% (N = 17) had received previous therapy or were treatment-naïve.

No antibody response was reported in patients with: indolent non-Hodgkin lymphoma (NHL; 25 of 60 patients), aggressive NHL (8 of 18), myeloproliferative neoplasms (MPNs; 6 of 76), and MDS (5 of 21). Only 1 of 101 patients with chronic myeloid leukemia had no antibody response.

The therapies associated with significant negative results were BTKs (Bruton tyrosine kinase inhibitors), immunoglobulins, and rituximab. By contrast, the TKIs (tyrosine kinase inhibitors) were associated with significant positive results.

For example, among the 6 patients with MPN, 5 patients received ruxolitinib therapy, and all 5 had no antibody response. By contrast, among patients with MDS, no correlation was found between negative vaccination response and a specific therapy.

“A substantial number of patients with hematologic diseases do not have adequate antibody response, and might therefore not have sufficient protection from vaccination,” said Dr Rotterdam. “We should recommend ongoing protective measures, such as masks, social distancing, and screenings, as well as prioritizing vaccination for family members and caregivers to protect the patients.”

Observational Study

The second study was an observational study of 46 patients with AML or MDS who were vaccinated with an mRNA COVID-19 vaccine at H. Lee Moffitt Cancer Center, in Tampa, FL. This study showed a strong antibody to mRNA vaccines in patients with AML and MDS.2

Of the 46 patients in the study (median age at vaccination, 68 years; 58.5% males), 69.6% were seropositive after the first vaccine, improving to 95.7% after the second vaccine, said Jeffrey E. Lancet, MD, Chair, Department of Malignant Hematology at H. Lee Moffitt Cancer Center.

“Antibody levels increased dramatically following the second vaccine dose, which indicated the potential utility of serial vaccination, with good efficacy in poorly responsive patients after the first vaccine dose,” Dr Lancet said.

Antibody titer levels were a mean of 3806 after the second vaccine dose versus 315 after the first dose (P <.0001), and these levels did not differ between patients with AML or MDS, he said. This difference was observed across different clinical and laboratory variables, including neutropenia and lymphopenia subsets.

The median time from cancer diagnosis to the start of vaccination was 24.3 months (range, 4.5-105 months). Of the 46 patients, 15 (32.6%) were receiving active cancer treatment at the time of vaccination.

Blood specimens were collected from patients before the first and second vaccine doses, and approximately 28 days after the second vaccine dose for antibody analyses. The seroconversion rate was not affected by age, gender, race, disease status, time to vaccination from disease diagnosis, number of previous lines of therapy, active therapy at the time of vaccination, neutrophil and lymphocyte counts, and transplant history, said Dr Lancet.

“In the patients who did not respond to the first vaccine dose, there were suggestions of patients who had either been on steroid therapy or immunosuppression as potential contributing factors to not converting after the first dose, but just about everybody converted after the second dose,” Dr Lancet said.

References

  1. Rotterdam J, Thiaucourt M, Schwaab J, et al. Antibody response to vaccination with BNT162b2, mRNA-1273, and ChADOx1 in patients with myeloid and lymphoid neoplasms. Blood. 2021;138(suppl 1):Abstract 218.
  2. Jain AG, Dong NC, Ball S, et al. Responses to Sars-Cov-2 vaccines in patients with myelodysplastic syndrome and acute myeloid leukemia. Blood. 2021;138(suppl 1):Abstract 217.
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