Tue. Dec 7th, 2021

With high mortality rates observed in myeloma patients with coronavirus disease 2019 (COVID-19) combined with the expected poor response to COVID-19 vaccinations, isolation periods are expected to increase, which will have a detrimental effect on the treatment of myeloma patients. Since the onset of the COVID-19 pandemic, myeloma patients have been screened, disrupting their therapy and health services, causing significant social isolation, and exacerbating mental health problems.

Study: Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyel treatment with vaccine-driven divergent T-cell response.  Image credit: Chinnapong / ShutterstockStudy: Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyel treatment with vaccine-driven divergent T-cell response. Image credit: Chinnapong / Shutterstock

Myeloma patients in the UK were offered both the mRNA-based (Pfizer BioNTech; PB) and viral vector-based (Oxford / AstraZeneca) vaccines. The recommended 12-week schedule for the second dose was also different from the manufacturer’s recommendations. It is important to understand the causes of poor vaccine response and potential rescue strategies, such as booster vaccination, to manage myeloma patients optimally.

A group of researchers from various institutes in the United Kingdom collaborated to address these evidence gaps by launching a web-based prospective study of adults diagnosed with multiple myeloma (MM) to determine the immune response to the first and second doses of the COVID-19 vaccine.

A pre-printed version of this study, which has yet to undergo peer review, is available at medRxiv* preprint server.

The study

There were 214 patients with myeloma or smoldering myeloma who completed the questionnaire in this study and who also gave a blood sample at least three weeks after the second dose of COVID-19 vaccine. Of the 214 patients, 160 reported the type of vaccine they received, with 59.6% of myeloma patients receiving the AstraZeneca vaccine and 44.4% of the smoldering myeloma patients. The remaining patients all received the PB vaccine.

In seven participants, there was serological evidence of a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, detected by the presence of Anti-N antibodies, six of these participants had myeloma, and one had smoldering myeloma. Between the first and second doses of COVID-19 vaccines, none of the participants developed a positive anti-N antibody status. Those who developed positive Anti-N antibodies showed higher Anti-S response at the time of the second test.

One of the patients showed an adequate anti-S antibody response after the first dose of the vaccine, not after the second dose. It was more common to observe a low Anti-S concentration in patients with partial response / stable disease or progressive / relapse than in patients in complete remission / very good partial remission. Compared to women, men were more likely to have low anti-S levels after the second vaccination.

No difference was observed in patients who achieved satisfactory Anti-S concentrations with either the PB or AstraZeneca vaccine. Nevertheless, patients receiving the PB vaccine showed higher concentrations of Anti-S antibodies. Low levels of Anti-S were also correlated with the treatment patients received, such as chemotherapy.

Following the second vaccine dose, the COVID-19 interferon-ϒ release assay (IGRA) was measured with results from 167 out of the 214 participants. Positive IGRA results were significantly associated with Anti-S serology status after the second vaccine dose. An IGRA-negative result was more likely to be seen in participants if they were not in full response / very good partial response, with no significant differences in chemotherapy status. A significantly higher IGRA rate was observed in patients who had received the AstraZeneca vaccine (70.6%) compared to those who received the PB vaccine (44.2%).

Men were more likely to have low Anti-S concentration compared to women, even after adjustments were made according to myeloma status. For participants receiving the AstraZeneca vaccine, IGRA reactivity rates remained significant after adjustment for gender, age, myeloma status, and chemotherapy. After adjusting for gender and age, analysis of the different combinations of Anti-S and IGRA status, progressive disease / relapse myeloma status predicted a dual negative status.

Implications

The results of this study show that a robust humoral anti-S antibody response can be produced in myeloma patients after vaccination with an mRNA-based vaccine. The proposed 12-week dosing interval is not detrimental to the immune response in myeloma patients.

Further study is needed regarding the durability of immune responses and the role of factors such as ongoing therapy. During patient follow-ups, the ongoing collection of data, including any occurrence of COVID-19 and the severity of the disease, will provide additional clinical significance of the immune response elicited after vaccination in myeloma patients.

*Important message

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered as crucial, guiding clinical practice / health-related behavior or treated as established information.

Journal reference:

  • Ramasamy, K. et al. (2021) “Immune response to COVID-19 vaccination is attenuated by poor disease control and anti-myeloma treatment with vaccine-driven divergent T-cell response”. medRxiv. doi: 10.1101 / 2021.10.21.21265158.

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