Results
A total of 19 cancer patients enrolled on study. Of these patients, one
died of disease prior to vaccination, 4 did not complete the series, and
three only had blood draws after boosters, leaving 11 evaluable
patients. Table 1 highlights the demographic and clinical
characteristics of these patients. There were 7 control patients,
including 5 who were > 6 months from cancer diagnosis and 2
followed for a benign hematology issue. Within the evaluable cancer
patients, the number of samples for each time-point were as follows: 6
pre-vaccination, 8 two weeks post vaccination, 8 four-six weeks post
vaccination, and 11 eight to twelve weeks after vaccination.
Among the 11 cancer patients analyzed, only 36.4% (n=4) had an adequate
B cell response (Figure 1). Of these four patients, one had Ewing
sarcoma on oral chemotherapy and another had Hodgkin lymphoma on
chemoimmunotherapy. The other two had leukemia, including a patient with
chronic myelogenous leukemia (CML) on an oral tyrosine kinase inhibitor
and one with acute lymphoblastic leukemia (ALL) on maintenance therapy.
It’s important to note that two of these four patients may have had
subclinical COVID infection prior to vaccination based on their
neutralizing antibodies. Patient 23 (with Hodgkin lymphoma), maintained
very elevated neutralizing antibodies despite extremely low blood
counts, however because we were unable to obtain a pre-vaccination
sample, it’s uncertain if he started with high antibody levels. The
patient with CML (Patient 3) had elevated neutralizing antibodies prior
to vaccination, suggestive of subclinical COVID infection. However his
titers continued to decrease over the 8-12 week period after
vaccination, suggestive of a waning response. The other seven subjects
had an inadequate B cell response, including one patient with Ewing
sarcoma on myelosuppressive intravenous chemotherapy. All other poor
responders were ALL patients in various phases of therapy, including
escalated IV methotrexate, delayed intensification, and oral maintenance
chemotherapy. Additionally, one of those patients (Patient 26) had
documented COVID infection in the middle of the vaccination series, and
despite this, still had an inadequate response.
Next, we measured T cell response after vaccination in pediatric
oncology patients. Of note, 9 patients had a sample for this analysis at
8-12 weeks. Adequate T cell response was seen in 77.8% of patients (n =
7). This includes Patients 3 and 21 with suspected subclinical COVID
infection and both solid tumor patients. Two leukemia patients with an
inadequate T cell response were in highly myelosuppressive phases of
therapy (Patient 2 and 16).
In order to understand what clinical factors may impact response to
vaccination, we analyzed vaccine response (by neutralizing antibody
levels) based on cancer diagnosis (hematologic vs solid tumor), absolute
lymphocyte count (ALC), and therapy regimen (Figure 2). Because the
majority of patients had leukemia, it was not possible to determine if
there were alterations in response based on cancer type. However, we did
note that the majority of patients with leukemia had an inferior B cell
response compared to healthy controls (Figure 2A). As previously
mentioned, the two patient who maintained similar levels of neutralizing
antibodies as the healthy controls (Patient 3 and 23) may have had
subclinical COVID prior to vaccination. There was no correlation seen
between ALC and B cell response, as ALC varied widely among both groups
(Figure 2B). In order to evaluate the relationship between chemotherapy
regimen and vaccine response, we reviewed the phase of therapy patients
were on at the time of vaccination and divided them into highly
myelosuppressive or less myelosuppressive (Figure 2C). We also focused
on the patients with a hematologic malignancy since there were only two
patients with solid tumors. Patients with highly myelosuppressive
therapy included those receiving escalated methotrexate, delayed
intensification, or early Continuation. Less myelosuppressive therapy
included oral targeted therapy and maintenance chemotherapy. There was
no difference in neutralizing antibody levels at any time point between
the two groups, suggesting that leukemia therapy in general was
associated with poor immune response to vaccination.