Study Finds COVID-19 Vaccine Is Safe in Patients With Hematologic Malignancies, but 25% of These Patients Do Not Produce Detectable Antibodies

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About one in four patients with blood cancer fail to produce detectable antibodies after COVID-19 vaccination, but results vary substantially by type of blood cancer, according to a study by Greenberger et al published in the journal Cancer Cell. Although earlier studies have shown that certain patients with blood cancer may not get optimal protection from vaccination, this study is the largest to date, examining over 1,400 patients, and the first to provide a detailed look across all major blood cancer and treatment types.

“Although some patients with hematologic malignancies will not mount a full antibody response compared to healthy individuals, vaccines are safe and offer protection to the majority of [patients with blood cancer],” said study coauthor Gwen Nichols, MD, Chief Medical Officer at the Leukemia & Lymphoma Society (LLS). “But not everyone will be protected, and [these patients] are at increased risk of serious illness and death from COVID-19. We encourage [patients with blood cancer] to take every measure to protect themselves from COVID-19 by getting vaccinated and continuing to take preventative precautions.”

The LLS estimates that nearly 250,000 patients with hematologic malignancies in the United States will not have detectable antibodies following COVID-19 vaccination. Dr. Nichols and the LLS also stress that when others get vaccinated, they are not only protecting themselves, but are helping to protect these patients and the millions of others in the United States with suppressed immune systems.

The study ( identifier NCT04794387) was made possible by the more than 8,000 current and former patients with blood cancer who joined the LLS National Patient Registry, a project of the Michael J. Garil Patient Data Collective. The Cancer Cell publication reported on 1,445 registry participants who had their antibodies measured at least 2 weeks after their second dose of one of the mRNA vaccines, which were by far the most commonly used during the period covered by the study—March 12 to May 5, 2021.

Seronegative Rates Vary by Blood Cancer Type and Treatment

The percentage of patients with non-Hodgkin lymphoma who were seronegative following vaccination ranged from 21% to 56%. This includes patients with diffuse large B-cell, mantle cell, marginal zone, and follicular lymphomas, as well as Waldenström’s macroglobulinemia. In contrast, just 1 of 64 patients with Hodgkin lymphoma was seronegative. Many of these patients were treated with anti-CD20 antibodies such as rituximab, which eliminates B cells that make antibodies.

Among leukemia patients, those with chronic lymphocytic leukemia (CLL) are most likely to be seronegative. More than one-third (36%) of patients with CLL were seronegative after vaccination. Nearly 3 in 10 of them had received no cancer therapy in the past 2 years, showing that the disease itself may impair the B-cell function needed to make antibodies to vaccines. However, the seronegative rates were even higher in CLL patients who were treated within the past 2 years with drugs that impair B cells, including Bruton’s tyrosine kinase inhibitors, anti-CD20 antibodies, or combinations of these therapies or their use with venetoclax, a BCL2 inhibitor.

Patients with multiple myeloma had higher rates of detectable antibodies compared to other blood cancers: only 5% of them were seronegative. Other studies have reported higher seronegative rates (up to 15%) in patients with multiple myeloma.

The investigators also examined the impact of chimeric antigen receptor (CAR) T-cell therapy on vaccine response. Six of seven patients who received CAR T-cell therapy for CLL, diffuse large B-cell lymphoma, or follicular lymphoma were seronegative after vaccination. In contrast, four of five patients who received a different type of CAR T-cell therapy for multiple myeloma produced robust antibodies. The registry is actively seeking additional patients who have received CAR T-cell treatment to increase the strength of its data.

Disclosure: This study was supported by the Leukemia & Lymphoma Society. The study authors reported no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.