A delayed third dose of the Moderna COVID-19 vaccine improves antibody responses in some immunocompromised patients with hematologic malignancies, according to a study published in JAMA Oncology

The study showed that a third vaccine dose, given 5 months after the second dose, could elicit antibody responses in blood cancer patients that were similar to those seen in healthy control individuals after 2 doses.

However, seroconversion rates were low in patients who recently received anti-CD20 therapy, CD19-directed chimeric antigen receptor (CAR) T-cell therapy, or hematopoietic cell transplant (HCT) and patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib.


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This study included 584 immunocompromised patients with hematologic cancers who received a third dose of the Moderna COVID-19 vaccine 5 months after the second dose. 

Overall, the third dose increased the seroconversion rate from 68.9% to 78.8%, and 67.3% of patients had a spike glycoprotein immunoglobulin G (S1-IgG) concentration of 300 BAU/mL or greater after the third dose. 

The researchers noted a significant correlation between serum S1-IgG concentration and pseudovirus neutralization of wild-type SARS-CoV-2, the delta B.1.617.2 variant, and the omicron BA.1 variant (P <.001 for all).

The researchers compared S1-IgG concentrations in the cancer patients with S1-IgG concentrations in 37 healthy control individuals who had received 2 doses of the Moderna vaccine. The results showed comparable median S1-IgG concentrations between patients and controls — 2171.3 BAU/mL and 1566.5 BAU/mL, respectively (P =.46). 

Seroconversion by Cancer and Treatment Type

The researchers also looked at seroconversion rates according to cancer and treatment types. The seroconversion rate was low among recipients of CD19-directed CAR T-cell therapy (35.0%).

The seroconversion rate was higher for allogeneic HCT recipients who had chronic graft-vs-host disease (92.0%) than for those who had undergone allogeneic HCT within the last 6 months (84.8%). 

Among lymphoma patients, the seroconversion rate was 22.5% during anti-CD20 treatment, 70.6% more than 12 months after completing anti-CD20 therapy, and 58.3% less than 12 months after autologous HCT. 

CLL patients had a higher seroconversion rate if they were being managed with a watch and wait approach (85.0%) than if they were taking ibrutinib (54.5%).

Seroconversion rates were consistently high in patients with multiple myeloma (88.9% or higher, depending on treatment), those with chronic myeloid leukemia on tyrosine kinase inhibitors (100.0%), those with acute myeloid leukemia or high-risk myelodysplastic syndromes (93.3% on hypomethylating therapy and 100.0% on high-dose chemotherapy), and those with myeloproliferative neoplasms taking ruxolitinib (96.6%). 

“Results of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination,” the researchers concluded. “Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Haggenburg S, Hofsink Q, Lissenberg-Witte BI, et al. Antibody response in immunocompromised patients with hematologic cancers who received a 3-dose mRNA-1273 vaccination schedule for COVID-19. JAMA Oncol. Published online August 11, 2022. doi:10.1001/jamaoncol.2022.3227