Strong Antibody Response to mRNA COVID-19 Vaccine Observed in AML, MDS

Jeffrey Lancet, MD

An observational single-center study suggests that mRNA-1273 SARS CoV-2 vaccination induces a strong antibody response in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), according to observational results presented during the 2021 ASH Annual Meeting.

Among 46 patients with AML or MDS vaccinated at Moffitt Cancer Center, 69.6% were seropositive after the first vaccine dose, improving to 95.7% after the second vaccine dose, reported Jeffrey Lancet, MD, at a press briefing delivered during the meeting.

“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,” said Lancet, chair of the Department of Hematologic Malignancies at Moffitt Cancer Center.

Antibody titer levels were a mean of 3806 after the second vaccine dose vs 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.

“Patients with myeloid malignancies, including AML and MDS, based on evolving data, are at high risk of severe COVID infection and death,” Lancet said. “Patients with AML and MDS frequently have quantitative and/or qualitative deficiencies of the white blood cells, including the neutrophils and sometimes the lymphocytes as well, as a result of either the disease itself or the treatment of the disease. It’s unclear whether these deficiencies would result in poor immune response to the COVID-19 vaccine, and to date, there has been very little reported on vaccine efficacy amongst patients with AML and MDS.”

The cohort of patients with AML or MDS in the study were part of a larger study of the immune response to mRNA-1273 vaccination in all patients with cancer. Of the 46 patients with myeloid malignancies included, 32 had AML and 14 had MDS and were, on average, about 2 years from diagnosis.

The median age at vaccination for the entire cohort was 68 years (range, 37.0-85.0). Patients were vaccinated between January 12 to 25, 2021. The majority of patients were male (58.7%) and Caucasian (95.7%). The median time from diagnosis to the start of vaccination series was 24.3 months, with a range of 4.5 to 105 months.

Fifteen patients were on active treatment for their disease at the time of vaccination. Treatments within 3 months of vaccination included hypomethylating agents in 6, erythroid maturation agents such as luspatercept in 2, an immunomodulatory drug in 1, and targeted therapy in 8 patients. A total of 32 patients (69.6%) had underwent allogeneic stem cell transplantation (SCT) for their disease. The median time since allogeneic SCT for the entire cohort was 17 months. Forty patients (87%) were in remission at the time of vaccination. Two patients with AML relapsed post-vaccination.

Blood specimens were collected from patients prior to the first and second vaccine doses (days 1 and 29) and approximately 28 days after the second vaccine dose (day 57) for antibody analyses.

The seroconversion rate was not affected by age, gender, race, disease status, time to vaccination from disease diagnosis, number of prior lines of therapy, receipt of active therapy at the time of vaccination (including targeted therapies), neutrophil and lymphocyte counts, and transplant history, Lancet said. “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.”

Antibody levels were significantly higher in patients with solid tumors in the study after the first vaccine dose compared with patients with AML/MDS, but this difference in antibody response disappeared after the second dose, said Akriti Jain, MD, a hematology/oncology fellow at Moffitt Cancer Center, during the oral abstract presentation.

The most common adverse events following vaccination were mild injection site pain (57.5%), fatigue (40%), headache (25%), and arm swelling (27.5%).

Even though therapy prior to vaccination did not affect antibody levels. the few patients on active treatment included in the study is a potential limitation, Lancet explained. In addition, patients on active aggressive therapy (ie, BCL-2 inhibitors) were not included because they were not being vaccinated at that time.

The findings need to be substantiated in a larger and more diverse cohort, the authors concluded.

Reference

Jain A, Dong N, Ball S, et al. Responses to SARS-CoV-2 vaccines in patients with myelodysplastic syndrome and acute myeloid leukemia. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 217.