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.