Following the 21st Century Cures Act passed in 2016, “real-world data and real-world evidence are playing an increasing role in health care decisions” (11, 12). Vaccination against SARS-Cov-2 is one of the best examples for generating real-world data due to the accelerated medical context that requires adaptation to more personalized medicine. Thus, one of the first question asked was the tolerance to vaccination which has been widely assessed for the normal population in prospective registration studies as well as by self-reporting of vaccination in a dedicated centralized registry and different government reports (13, 14). In patients with cancer or especially HM, tolerance has only been reported in association with immunogenicity studies also based on self-reported analyses (15). To our knowledge, no analysis has been made using a simple questionnaire included in a telemedicine application used for the first patients vaccinated in our Institute. At the beginning of the vaccination campaign, when new side effects appeared especially for a new type of vaccines, a misunderstood message appeared in this context leading to a more complexed acceptance of COVID-19 vaccines. We therefore used such a tool to promote better patient adherence to the new vaccine and to definitively confirm the good tolerance in such a patient population. Indeed, COVID-19 vaccine hesitancy is relatively evenly distributed across the population, closely related to identifying collective importance but this was likely less observed in a population with cancer (16). In our survey including 43 patients followed with the telemedicine application, there was no patient refusing vaccination and only one among the following patients. This process is planned to be developed in other vaccination campaigns, such as pneumococci or influenza. Furthermore, this telemedicine application is now being developed in different fields for other types of medical monitoring in combination with an electronic pill dispenser.
Additional questions relate to the policy of vaccination against COVID-19, especially for patients with HM who have shown a heterogeneous response to vaccination as mentioned in a recent meta-analysis and subgroup analyses (17). According to the OnCovid registry, vaccination against SARSCoV-2 was associated with a decrease in morbidity and mortality related to COVID-19 in cancer patients including 346 patients with HM (18). There were a difference mortality rates at 14 and 28 day between fully vaccinated and unvaccinated patients, respectively 5.5% vs 20.7% (P = 0.0004) and 13.2% vs 27.4%, (P = 0.0028). Fully vaccinated patients had fewer sequelae than unvaccinated patients (6.7% vs 17.2%, P = 0.0320) (19). This suggests that seroconversion and presumably serological level must influence COVID-19 morbidity and mortality in cancer and reinforces the need to verify the specific immune response by monitoring this response by adapting the strategy on a personalized basis. In addition to the threat posed by acute morbidity and mortality from COVID-19 in cancer patients, recent evidence highlights that the continuity of oncology care may be further disrupted by the long-term consequences of COVID-19, which affect approximately 15% of cancer patients recovering from the acute phase (19). Recommendations for vaccination were made for elderly people with systematic vaccination every 6 months with no serological monitoring (20). For immunocompromised people, recommendations are not clear, particularly the number of boost vaccines, and the time to use antibody therapy such as casirivimab-imdevimab (Ronapreve®) or tixagevimab/cilgavimab (Evusheld®) (21–23). In addition, for patients with HM, only general expert recommendations were available, based on experience from cohort analysis and/or meta-analysis (24).
Immunodeficiency due to disease or treatment is well known to negatively impact seroconversion after vaccination, as observed after influenza vaccine, including H1N1, and pneumococcal, particularly after allograft or chimeric antigen receptor (CAR) T-cell therapy (25–27). The heterogenous humoral response in HM was due to the alteration of the B-cell compartment that is usually observed after the therapies used in HM (28). Specific cellular response against SARS-Cov-2 has also been described as heterogeneous in HM and not always correlated with the humoral response (29). This observation may complicate the interpretation of the specific immune protection of these patients. Thus, there are several clinical options, including routine vaccination every 6 months, or monitoring of cellular and serological immune response for all patients or monitoring of serological response only. The first option is an epidemiological response based on the apparent reduced severity of COVID-19 in patients who have a full vaccination in cancer patients and is not personalized medical follow-up. Monitoring humoral and cellular immune response is not possible due to cost, although there are new bioassays to monitor both, including commercially available assays for T-cell response but of little practical use (30, 31). Only RST monitoring of the humoral response is simple, giving a semiquantitative response sufficient for monitoring as we observed.
While third-dose boosters are effective for most individuals with cancer, increasing protection against coronavirus, their effectiveness is heterogenous and lower than in the general population (32). Many cancer patients will remain at increased risk of coronavirus infections even after 3 doses. This is probably due to a lack of immune efficacy in some patients that must be identified to protect them with neutralizing antibodies. Our study suggests that if patients had no serological response after 2 vaccines, it is probably best to use such therapies. The use of such neutralizing antibodies does not totally protect against COVID-19 but may likely reduce viral load to limit disease severity as we have observed.
Additionally, the emergence of the B.1.1.7 and B.1.351 variants has raised concerns about reduced vaccine efficacy and increased reinfection rates (33). In healthcare workers, after the second dose, the sera effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, while the neutralization of the B.1.351 variant was reduced five times, indicating some protection in normal people (33). However, in HM patients, this may correspond to the lack of immune protection.
In conclusion, due to the heterogeneity of seroprotection against COVID-19 in HM, there is a need for personalized dynamic monitoring in the context of immune protection after vaccination, especially against COVID-19 and probably in different clinical situations such as standard vaccination for the high-risk person. The ability to use RST makes this possibility more available.