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Results from 2 Studies Provide Insights on Antibody Response to COVID-19 Vaccines in Patients with Hematologic Malignancies

February 2022, Vol 13, No 1 Online Only

Results from 2 single-center studies presented at the ASH 2021 Annual Meeting and Exposition showed that nearly 1 in 6 patients with hematologic diseases had no or low antibody response after a second COVID-19 vaccination, but that the mRNA 1273 COVID-19 vaccine induced a strong antibody response in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Antibody Response in Patients with Myeloid and Lymphoid Malignancies

Jil Rotterdam, MD, Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Germany, presented findings from an observational study, which showed that approximately 15% of patients with hematologic disorders had a negative antibody response at least 2 weeks after receiving their second COVID-19 vaccination. Although it is encouraging that 85% of patients did show an antibody response following vaccination, she said, the results from this study suggest that additional precautions may be necessary to prevent COVID-19 infection in these vulnerable individuals.

The researchers recruited 373 patients who were treated for hematologic disorders at the University Hospital Mannheim in Germany. Of the 338 patients with hematologic malignancies enrolled in the study, 67% had myeloid neoplasms and 33% had lymphoid neoplasms. Thirty-five vaccinated patients with nonmalignant hematologic diseases served as the controls. More than 80% of the patients received 2 doses of mRNA vaccines. Overall, 229 (61%) patients with hematologic malignancies were on active therapy and 39% were previously treated or treatment naïve. Vaccine-related antibodies were measured at a median of 12 weeks after final vaccination.

Approximately 85% of patients tested positive for vaccine-related antibodies and 15% tested negative. The rate of negative antibody results was highest among those with lymphoid neoplasms—a group of diseases that include lymphoma, myeloma, and lymphoid leukemia. Among these patients, 36% tested negative for vaccine-related antibodies. Patients with indolent non-Hodgkin lymphoma had the poorest response to vaccination overall.

Of the patients with hematologic malignancies and a negative vaccination response, 71% were on active therapy and 29% were previously treated or treatment naïve.

Therapies associated with significant negative results included Bruton tyrosine kinase inhibitors, immunoglobulins, and rituximab (Rituxan). Tyrosine kinase inhibitors were associated with significant positive results. Five of 6 patients with myeloproliferative neoplasms had a negative antibody response, and all 5 of these patients had received ruxolitinib (Jakafi) therapy. Among patients with MDS, there was no correlation 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.”

Antibody Response in Patients with AML and MDS

Jeffrey Lancet, MD, Chair, Department of Hematologic Malignancies, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, presented findings from an observational study evaluating antibody response to the mRNA 1273 COVID-19 vaccine in patients who had been treated for AML and MDS at his center. Results showed that after the first vaccine dose, 69.6% of patients had an antibody response and after the second dose, 95.7% had an antibody response.

“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,” he 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. This difference was observed across different clinical and laboratory variables, including neutropenia and lymphopenia, and subsets.

The researchers recruited 46 patients who either had previously or were currently undergoing treatment for AML or MDS. The median age at vaccination was 68 years. Most patients were male (58.7%) and Caucasian (95.7%). The median time from diagnosis to the start of vaccination series was 24.3 months (range, 4.5-105 months). Fifteen (32.6%) patients were receiving active treatment for their disease at the time of vaccination.

Blood specimens were collected from patients prior to 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, sex, race, disease status, time to vaccination from disease diagnosis, number of previous lines of therapy, receipt of active therapy at the time of vaccination (including targeted therapies), 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 that 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.”

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