COVID-19 Vaccination Induces High Seroconversion Rates in Patients With Cancer, But Novel Strategies Needed for Select Subsets

Balazs Halmos, MD, MS

COVID-19 mRNA vaccines have been shown to result in high rates of seroconversion in patients with cancer, although certain patient subgroups like those with hematologic malignancies or those who received prior immunosuppressive therapies may be less responsive or have lower immunogenicity following vaccination, according to Balazs Halmos, MD, MS. As such, more research efforts need to be focused on exploring novel booster strategies or passive immunization approaches in these patients.

In a recent study, Halmos and colleagues examined seroconversion rates following administration of a COVID-19 vaccine in patients with cancer. Unlike prior smaller studies, results demonstrated a 94% seroconversion rate in 200 patients with cancer who had received full dosing with an FDA-authorized vaccine.

Although patients with solid tumors had a rate of 98%, those with hematologic malignancies, those who received highly immunosuppressive therapies like CD20-targeted agents, and those who underwent stem cell transplantation experienced significantly lower rates of 85%, 70%, and 73%, respectively. Notably, patients who were receiving treatment with immune checkpoint inhibitors or hormonal therapies experienced a high seroconversion following vaccination, at 97% and 100%, respectively.

“The message is that everyone should get vaccinated. However, further studies will need to be performed for specific cohorts of patients,” Halmos said. “Some of those patients remain vulnerable, and we, as a community, need to protect them. We will have to [make] our own effort to get vaccinated, and [ensure that] our friends and family get vaccinated. Also, these patients are likely going to wear masks a little bit more than others, and they are going to be a little bit more protective with regard to social distancing.”

In an interview with OncLive^® Halmos, director of Thoracic Oncology and director of Clinical Cancer Genomics at Montefiore Medical Center, further discussed a study examining the effectiveness of COVID-19 vaccination in patients with cancer and identified important areas for future research.

OncLive^®: What are some of the ways in which COVID-19 has impacted patients with cancer?

Halmos: This has been a very difficult year for all of us, but very specifically for our patients with a cancer diagnosis. They have had to suffer both the direct consequences of the pandemic, but also a lot of indirect [challenges], with a lot of fear and anxiety complicating things [even further]. We learned here, in New York City, very early on, that the direct morbidity and mortality of COVID-19 is tremendous for our patients with cancer. The elderly, the frail, [and those] with different hematological malignancies [have] very high mortality.

Also due to the pandemic, many of the usual cancer screening studies have been delayed, patients are being diagnosed at later stages, they are fearful to come to the doctor, the doctor is not accessible, and we are making different changes [to their treatment] to adapt to the [situation]. So many compromises have been made in that regard. [However,] it is time to try to pull together and pull our patients out of this pandemic in the most rapid way possible.

What inspired this research, and what is currently known about COVID-19 vaccination in patients with cancer?

What inspired [this work] is the need to learn, and the need to move on. As I mentioned, we got hit very early in New York City [during] the pandemic. As a result, we were one of the earliest institutions to put together a cohort experience summing up the impact of COVID-19, which [we know] is terrible. We wanted to learn from that. We looked at the post–COVID-19 experience [and asked]: Who are the patients who are surviving COVID-19, and how do they respond to it? We have learned through work that we published a couple of months ago, that most of our patients respond quite well to COVID-19 challenge in terms of developing immunity against [the virus], except for certain cohorts of patients like those [who underwent a transplant] and those [who had received] highly immunosuppressive therapy.

We felt that we needed to learn more about these populations as we tried to vaccinate our patients. We were very proactive. [We, at] Montefiore Medical Center, [vaccinated our] patients as early as possible, starting in January [2021]. As a result, we were able to put together a cohort with an early experience post-vaccination. [Here, we sought to determine whether] patients responded [to vaccination], if they respond as well as others, if the vaccine was safe, and whether certain patients would suffer from more safety issues, such as those receiving immunotherapy. There was zero knowledge as to [whether these patients] have a higher chance of experiencing adverse reactions. [We also wanted to know, how] these immunosuppressed patients [would] respond [to the vaccine], and whether they would respond at all. This was very much needed information. We feel very fortunate that we have been able to contribute to this [collective] knowledge [base].

What were the methods used for this research, and could you provide a snapshot of the specific population that had been included in the analysis?

This was cross-sectional research looking at our patients [who] come into the clinic here, at Montefiore. [They are] a very diverse group, both in terms of age range and ethnicity; approximately one-third of them were African American and one-third [were] Hispanic. [As such, it was] a very comprehensive cohort in [that it included] the different populations that up the United States and New York City specifically.

On top of that, [this was] also a diverse group of patients with regard to diagnosis, [patients with] solid tumors and hematologic malignancies were well represented, and the types of treatments they received or were still receiving on an ongoing basis, such as chemotherapy, immunotherapy, and bone marrow transplantation. The cohort was also very large. Overall, we [accrued] about 250 patients to start with, with the help of a tremendous group of hematology/oncology fellows.

What were some of the key findings from the study?

The little snippets of information that came out beforehand were frightening. [We were hearing that] many of the patients with cancer did not respond to the vaccines, only about 20% or 30%. [However], when you look at those little experiences, [those results were on patients who] just [received] a single dose [of the vaccine]—not both doses, [or they were] looking at a very select group of patients. [Regardless, it was] very frightening information.

Our cohorts suggest the complete opposite. We saw very encouraging [data] showing that most patients with a cancer diagnosis have a really high chance of responding to vaccinations—as long as the vaccinations are done in an appropriate manner, [with] both doses administered; [this was true] even for [patients who were receiving] active treatment with chemotherapy, targeted therapy, or immunotherapy.

We measured this by using a validated antibody assay against SARS-CoV-2 spike protein [and looked at anti-spike IgG titers]. We found that about 95% of our patients mounted an immune response [to vaccination]; this was very close to [what was seen in] the control population. We also had the chance to look at the titer levels, not just positive vs negative, but the actual values of how much antibody was generated. By and large, patients with a solid tumor mounted a similar immune response to [that seen in] an average patient population without a cancer diagnosis.

The data were very encouraging on one end, but we had very specific observations on the other end. For example, we saw that for some patient cohorts, generating an immune response will be difficult; this goes with our logic. Many of our patients are highly immunosuppressed after bone marrow transplantation, anti-CD20 therapy, or CAR T-cell therapy. We have seen this in our previous cohort post COVID-19. We projected that we might see it. Of course, there is a vast amount of transplant literature showing that vaccinations are not very efficacious in these patients. Although we saw a lesser chance of seroconversion in those patients, about 70% to 75% of these patients [still] converted.

Research efforts need to be made to [identify whether we] can somehow do better with regard to generating immunity [in these patient subsets] by using unique vaccination schedules or by providing them with passive immunity through antibody approaches. [This is] certainly just the foundation for more research efforts [for] everyone to promote and participate in.

As of right now, how should vaccination be approached for these at-risk subsets of patients?

For most of the patients, they should still be vaccinated as early as possible. they should be vaccinated with the standard schedule. [We] currently [don’t have any] studies [focusing on this], which is disappointing. We need to be a little bit faster setting up our studies [examining] novel booster strategies. Hopefully, [these studies] will be opening soon, so [patients] who are interested can be guided toward them. For transplant patients, there is general knowledge that, for example, within 3 months after transplant, there is no point in vaccinating [at that time point]. In some subsets of patients, delaying until after recovery of immunity will be the right thing to do. There are guidelines on this that are coming out [to help] guide [us] to take the proper approach.

Out of all the data collected, did any specific findings stand out to you that should be highlighted?

One intriguing finding [was that we saw a] bit of a differential benefit between the vaccines. The mRNA vaccines generated a better titer than the Johnson & Johnson vaccine. That goes along with common knowledge outside of the hematologic/oncology community.

Also, we had about 20 patients who had COVID-19 before. By and large, those patients mounted a fantastic immune response [to vaccination]; this been seen before. However, in a way, it is a nice confirmation that our cohort represents reality. After a COVID-19 infection, the vaccines work super well.

Lastly, we noticed a couple of small cohorts of patients [who had] less than a chance of immunity who will need to be studied further. [This included] patients [who received] certain therapies, such as BTK inhibitors, which might make sense because those agents block B-cell function. Also, patients [who received] CDK4/6 inhibitors seemed to have lesser titers. However, these are small cohorts. We [are not necessarily] seeing anything very definitive about them. [We might be able to learn more] in a larger cohort; we need to look at these very specific subsets [in future efforts].

Are any next steps planned for this research? What are some additional areas of opportunity?

Well, these have been areas of real need. As an institution with a very large number of patients hit early with COVID-19, [there is a] drive coming from our faculty and fellows to ensure that we contribute to not just take care of [patients] but protect them and research better ways to treat them. Many opportunities for research exist.

We are reaching out right now to different friends, researchers, and industry to see whether booster vaccine strategies could be potentially initiated for patients with hematologic malignancies, for example. We have seen a couple of papers [looking at] cross vaccination [and we’re seeing that] going from vaccine A to vaccine B can be highly efficacious, for example. That could be a really interesting method. Hopefully, we will be able to pursue it. But if others open such a study, please give me a call and we will be able to participate.

What is your advice to your colleagues regarding vaccination in patients with cancer? What should be taken away from this work?

The sense of encouragement. We are ending this final phase of the pandemic. We should be able to allow our patients with cancer to emerge, not just in terms of being able to continue with their treatment, but to be able to be part of society and community if we vaccinate them early on. But yes, indeed, there are some subsets of patients who will need more attention. Research needs to continue.

Reference

1. Thakkar A, Gonzalez-Lugo JD, Goradia N, et al. Seroconversion rates following COVID-19 vaccination among patients with cancer. Cancer Cell. Published online June 5, 2021. doi:10.1016/j.ccell.2021.06.002