Retrospective Study of COVID-19 Vaccines in Patients Undergoing Immunotherapy for Cancer.

The recent outbreak of Coronavirus 2019 (COVID-19) caused by a new zoonotic coronavirus
SARS-Cov-2 poses a major public health threat, with at least 100,000,000 people infected
worldwide by the end of January 2021 and over 2 million deaths. Given the scale of the
pandemic, it has become imperative to quickly develop a vaccine and over 30 vaccine
candidates have entered clinical evaluation. The first vaccine to receive marketing
authorization in Europe and France was an mRNA vaccine, Comirnaty® (Bnt162b2;
Pfizer/BioNtech). In a Phase III study of 43,448 participants, after a median follow-up of 2
months, the number of cases of COVID-19 was 8 in the vaccine arm vs. versus 162 in the
placebo arm, respectively, with 1 versus 9 serious cases (Polack et al. 2020). Adverse events
occurred in more than 50% of vaccinated participants and included local reactions as well as
frequent systemic reactogenicity such as fatigue and headache. Fever occurred in about 15% of
the participants who received the vaccine. The second vaccine to be licensed was also an mRNA
vaccine: the Moderna COVID-19 mRNA (nucleoside modified) vaccine (mRNA-1273, Moderna). A
Phase III trial involving 30,420 volunteers reported efficacy and safety comparable to the
Pfizer/BioNtech vaccine. A severe form of COVID-19 occurred in 30 subjects, with one death;
all 30 cases were in the placebo group. Moderate and transient reactogenicity after
vaccination occurred more frequently in the mRNA-1273 group.

Serious adverse events were rare and the incidence was similar in both groups. Within the
vaccination strategy implemented on a national level, the Comirnaty® vaccine
(Pfizer/BioNtech) and the Moderna COVID-19 mRNA vaccine (nucleoside modified) may be used
interchangeably, depending on logistical constraints.

For several weeks now, the Oxford-AstraZeneca chimpanzee adenovirus vector vaccine ChAdOx1
nCoV-19 (AZD1222) has been available in France and its efficacy and safety of use have been
evaluated. Also the non-replicating viral vector (adenovirus) vaccine for CVD 19 from Janssen
Laboratories (a subsidiary of Johnson & Johnson; other names: Ad26COV2.S; JMJ Vaccine or J &
J COVID-19 Vaccine) was launched in France a few weeks ago. Its efficacy and safety have been
validated in a phase III trial. A number of other candidate vaccines using various techniques
such as mRNA, protein subunit, viral vector or inactivated vaccines are currently under
investigation and will be available soon.

Cancer patients are particularly at risk of developing a severe form of COVID-19. Patients
with solid tumors appear to be at a greater risk, particularly in the first year after
diagnosis. Severity and mortality rates in the COVID-19 and Cancer Consortium (CCC19)
registry and other cohorts range from 5% to 61% (a meta-analysis showed 26%), which is well
above the general population. Although data on vaccination in cancer patients are limited,
there is sufficient evidence to support anti-infective vaccination in general, even in cancer
patients on immunosuppressive therapy. In its notice dated January 25th, 2021, the National
Cancer Institute defined its recommendations for prioritizing cancer patients for vaccination
against SARS-CoV-2. This report stresses that the data acquired from science is limited in
quantity and quality concerning the emerging field of vaccination against SARS-CoV-2 and even
more so in sub-populations including cancer patients. It reminds us that the challenge
remains to vaccinate the entire population of patients who have or have had cancer, i.e.
approximately 3.8 million people.

The level of efficacy can be expected to be generally reduced in certain cancer patient
populations with intense immunosuppression, such as haematopoietic stem cell transplant
recipients. However, based on extrapolation of data from other vaccines and the mechanism of
action of COVID-19 (non-live) vaccines, it is conceivable that the efficacy and safety of
COVID-19 vaccination could be estimated to be similar to that of non-cancer patients,
although data from clinical trials are lacking. The efficacy and duration of immunity in
cancer patients is still unknown and unexplored. It is therefore legitimate to propose
surveillance through dedicated registries and clinical trials. Furthermore, close monitoring
and follow-up of cancer patients is required after COVID-19 vaccination to assess potential
adverse events and measure clinical outcomes, e.g. infection, severity and mortality from
COVID-19, cancer complications etc… The investigators wish to set up a
pharmaco-epidemiological cohort within the Hospital Territorial Groups of the Cévennes-Gard
Camargue, East-Hérault and Haute-Garonne and West Tarn on a specific population, patients
undergoing immunotherapy for cancer, as currently there is no data available under "real
life" conditions following anti-COVID vaccination19. Our hypothesis is that patients
undergoing immunotherapy will not develop more vaccine-related adverse events than those
observed in the efficacy and safety validation studies of the BNT162b2 mRNA Covid-19,
mRNA-1273 SARS CoV-2, Oxford/AstraZeneca and Ad26COV2.S, JMJ Vaccine or J & J COVID-19
Vaccine.