By Victoria Forster, PhD; originally published April 29, 2022

One theory is that the Moderna vaccine may be more effective because it contains more mRNA. Source: Getty Images

Growing evidence suggests that patients with cancer have better responses to the Moderna COVID-19 vaccine than to the Pfizer-BioNTech vaccine.1-6

Studies designed to monitor the level of immune response after vaccination have revealed a difference in protective antibodies between patients who received the Pfizer-BioNTech and Moderna vaccines, raising questions as to whether patients with cancer should preferentially be given the latter.

One of these studies was recently presented at the NCCN Annual Meeting.1,2 The study involved 240 patients with chronic lymphocytic leukemia (CLL) and other non-Hodgkin lymphomas (NHLs) who were tested for post-vaccination antibodies. The cohort included patients who were and were not receiving active treatment. 

The results showed that patients with CLL had better antibody responses after completing a vaccination series with the Moderna vaccine than with the Pfizer-BioNTech vaccine. The rate of antibody response was 61% with Moderna and 44% with Pfizer-BioNTech (P =.028).

For patients with other NHLs, the largest share of whom had Waldenstrom macroglobulinemia (WM), a difference in response was noted but did not quite reach statistical significance. In the WM group, the antibody response rate was 88% with the Moderna vaccine and 54% with the Pfizer-BioNTech vaccine (P =.11). For the remaining NHL patients, the antibody response rate was 80% and 70%, respectively (P =.56).

“When we started this study, we were not really thinking that different vaccines may give different responses,” said Shuo Ma, MD, PhD, senior author of the work and an oncologist and associate professor of medicine at the Feinberg School of Medicine at Northwestern University in Chicago.

“We wanted to look at our patient population in general to assess response to the vaccines. Finding a higher response with the Moderna vaccine compared to Pfizer in certain patient populations was a surprise to us.” 

Types of Response

In their study, Dr Ma and colleagues assessed antibody titers using the Access SARS-COV-2 assay. An antibody response was defined as a positive total antibody or spike protein antibody result.

“Looking at spike protein antibodies as a measure of response is a very convenient way for us to look at the vaccine response in clinical practice, but there are several caveats,” Dr Ma explained. “We are not using a neutralizing antibody assay, and other cellular responses can occur.” 

Dr Ma added that she is currently conducting research looking at T-cell responses in patients with CLL and other NHLs. 

A study in which researchers did look at neutralizing antibodies, among 238 patients with multiple myeloma, showed that 54% of vaccinated patients overall had detectable levels of neutralizing antibodies.3,4 

The prevalence of neutralizing antibodies was 67% among patients who received the Moderna vaccine and 48% among patients who received the Pfizer-BioNTech vaccine (P =.006). 

Another study included 500 patients with a variety of solid and hematologic cancers, as well as 137 other immunocompromised patients and 204 healthy control individuals.5,6 

In this study, the duration of neutralizing antibody response in patients with solid cancers was significantly longer after the Moderna vaccine (range, 221-226 days, depending on the SARS-CoV-2 variant) than after the Pfizer-BioNTech vaccine (range, 146-161 days). 

Explaining the Difference

The Moderna and Pfizer-BioNTech vaccines are similar and “both very good vaccines,” according to Tania Watts, PhD, a professor of immunology at the University of Toronto in Ontario, Canada. 

She noted that there may be some subtle differences in their formulations, “but broadly, they are mRNA and a lipid nanoparticle, so are similar vaccines.”

As evidence continues to emerge supporting the notion that Moderna may be more effective for patients with cancer and other immunocompromised patients, one underlying reason could simply be that this vaccine contains more mRNA.

The Moderna and Pfizer-BioNTech vaccines both underwent dose-escalation studies in the initial clinical trials when they were tested on humans. Pfizer settled on a dose containing 30 μg of mRNA (for vaccination in adults), and Moderna settled on a dose containing 100 μg of mRNA (for the primary doses in adults).7,8 

Dr Watts said the idea that more mRNA leads to more antigen production “is the most likely explanation” for the differences in responses between the 2 vaccines. She added, however, that “you’d really have to do a dose-escalation with the 2 side by side to really confirm that.” 

The concept of a larger amount of antigen stimulating a greater immune response is not new, Dr Watts noted. Flu vaccines for older people frequently contain higher doses of antigen than those used for younger, less clinically vulnerable populations.

“For a number of years now, there’s been a high-dose flu vaccine offered to people over 65, because it’s well known that our immune system gets weaker with age. So just giving more of the vaccine in this case is known to give a better response,” Dr Watts explained.

Implications for Practice

On the basis of all the current and accumulating evidence, should cancer patients and other clinically vulnerable people be receiving the Moderna vaccine instead of the Pfizer-BioNTech vaccine?

“I think that is a reasonable suggestion,” Dr Watts said. “And in fact, I believe various clinicians are already recommending this informally for their patients. If someone’s already had a course of Pfizer vaccine, and they’re ready for another booster, going for Moderna is not a bad idea. Whereas, for someone who is a healthy person under 65, I think there’s no reason not to just choose any of the available vaccines for the booster.”

“I can tell you, in my clinical practice, most of my patients have finished their primary vaccine series and we are more talking about boosters,” Dr Ma said. “After this study, I’m starting to recommend that they consider using Moderna for their booster.”

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