Vaccine: HEP
Symptoms: Inappropriate schedule of product administration
Clinical narrative: Drug Interaction with Burton tyrosine kinase inhibitors (BTKi's); HEPLISAV-B given at 0 and 3 months; Median anti-HBS titer was 0.05 mIU/mL with BTKi treatment; Initial report received on 21-Mar-2025.  This report was retrieved from the following publication:   The patient was enrolled in an open-label, phase 2 clinical trial of recombinant adjuvanted hepatitis B vaccine (HEPLISAV-B) in patients with treatment naïve (TN) chronic lymphocytic leukemia (CLL) or those on Bruton tyrosine kinase inhibitors (BTKi's) for >= 6 months frontline treatment or for relapsed disease.  The patient did not have a history of hepatitis B infection nor immunization confirmed by negative hepatitis B surface antibodies (anti-HBs) and hepatitis B core antibodies.  Concomitant medications included BTKi treatment with either ibrutinib or acalabrutinib.  Hepatitis B serologic titer was measured at baseline, prior to receiving the first dose of HEPLISAV-B.  On an unknown date, the patient received dose 1 of HEPLISAV-B   (lot #, expiration date, site and route not reported).  On an unknown date, three (3) months after receiving the first dose of HEPLISAV-B, the patient received dose 2 of HEPLISAV-B (lot #, expiration date, site and route not reported).  On an unknown date, six (6) months after receiving the first dose of HEPLISAV-B, serologic titers were measured. The patient experienced did not respond to HEPLISAV-B vaccination.  The study confirmed that HEPLISAV-B administration is safe for patients with CLL, with similar rates of adverse events compared with healthy individuals. At baseline, comparing TN vs BTKi groups, the median absolute lymphocyte count was 23.0 (11.72-57.59) vs 4.14 (1.86-7.33) k/microL; immunoglobulin IgG was 652 (535-782) vs 474 (417-759) mg/dL, and beta-2-microglobulin was 2.1 (1.7-2.4) vs 2.0 (1.68-2.33) mg/L. Only 1 patient on BTKi responded, whereas 9 patients who were TN responded to HepB-CpG.  It was noted that at six months, the median anti-HBS titer was 0.05 mIU/mL (interquartile range [IQR], 0.00-0.43 mIU/mL} in the BTKi group and 1.30 mIU/mL (IQR, 0.15-43.78 mIU/mL} in patients who were TN.  No difference was noted between serum anti-gE antibody titer at baseline or at 6 months between patients who were BTK-treated and TN. BTKi's, a standard treatment in B-cell malignancies, were associated with near absence of de novo humoral immune response to HEPLISAV-B.   In summary, CLL patients have impaired vaccine responses compared with the general population.  The humoral immune response to novel antigens is abrogated by BTKi's.  Vaccination against novel antigens would ideally be scheduled early in the disease course and before starting BTKi.  No additional information was reported.   Company Comment: The company assessed the events as non-serious. The event of vaccination failure was not immunologically confirmed as the dosing schedule of vaccine administration was not according to schedule. Although there is a virtual absence of a de novo humoral response to HepB-CpG on BTKi therapy, patients with TN CLL could be more immunocompetent because of less advanced disease (at baseline, median time from diagnosis was 58 months for TN vs 104 months for those on BTKi therapy), permitting more effective immune responses.; Sender's Comments: The company assessed the events as non-serious. The event of vaccination failure was not immunologically confirmed as the dosing schedule of vaccine administration was not according to schedule. Although there is a virtual absence of a de novo humoral response to HepB-CpG on BTKi therapy, patients with TN CLL could be more immunocompetent because of less advanced disease (at baseline, median time from diagnosis was 58 months for TN vs 104 months for those on BTKi therapy), permitting more effective immune responses.