Top Ten Poster Award: HOPA 13th Annual Conference

Sarah K. Kraus, PharmD BCOP BCPS
Hematology/Oncology Clinical Pharmacy Specialist
Pennsylvania Hospital
Philadelphia, PA

HOPA’s annual conference provides an opportunity for hematology/oncology practitioners to receive comprehensive education on a variety of topics. Programs at the conference include in-depth analyses of treatment strategies, summaries of the latest drug developments, and reviews of novel practice models. In particular, the poster presentations at the conference highlight the innovative work of our members in the areas of clinical and translational research and practice management.

Each year, more than 100 posters submitted by residents, fellows, and students are presented at the conference. Members of HOPA’s Research Abstract Review Work Group use a blind review process to select the Top Ten Posters from all the posters submitted and then with additional volunteers on site select the recipient for the Top Ten Poster Award. The recipients of this award have conducted original, well-designed studies that can influence hematology/oncology pharmacy practice. The 2017 recipient of HOPA’s Top Ten Poster Award is Benjamin Andrick, PharmD, PGY-2 hematology/oncology resident at Augusta University Medical Center, Augusta, GA.

Dr. Andrick is recognized for his research titled “Pneumococcal Vaccine Response in Chronic Lymphocytic Leukemia Patients Receiving Ibrutinib.” Patients with chronic lymphocytic leukemia (CLL) have impaired immunity resulting from defects in both the humoral and cellular immune pathways. Subsequently, these patients are at a higher risk of infection-related morbidity and mortality. The Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices recommend that patients with CLL receive the 13-valent pneumococcal conjugate vaccine (PCV13) for protection against pneumococcalinfections. However, if these patients have previously received B-cell-depleting anti-CD20 therapies, the recommendation is to wait to administer PCV13 until at least 6 months following the last dose, because patients may not mount an adequate immune response if the vaccine is administered earlier. Ibrutinib, a first-line agent for CLL, works by covalently binding to and inhibiting Bruton’s tyrosine kinase (BTK), which is constitutively active in CLL cells. BTK inhibition ultimately leads to impairment in malignant B-cell proliferation, adhesion, and trafficking. Because ibrutinib affects the B-cell signaling pathway, Dr. Andrick and colleagues hypothesized that ibrutinib would attenuate PCV13 vaccination response.

The first objective of this study was to determine whether concurrent administration of PCV13 and ibrutinib generates an adequate vaccination response, defined as at least a ≥ twofold titer increase in ≥3 serotype-specific IgG antibodies postvaccination compared to baseline IgG levels. For the second objective, to further evaluate IgG antibody response to the vaccine, SAMSN1 (Src homology domain 3 lymphocyte protein 2, also known as HACS1) and BTK expression was evaluated. SAMSN1 displays an inhibitory role on B-cell proliferation and differentiation processes. Prior to this study, increased SAMSN1 expression had been correlated with impaired pneumococcal vaccine response. The third objective was to determine whether changes in HACS1 correlated with attenuated pneumococcal vaccine response.

This study was an institutional review board–approved prospective pilot cohort study. Adult patients with CLL receiving ibrutinib 420 mg by mouth daily (active arm) or active surveillance (control arm) were included. Patients were excluded if they had received the PCV13 vaccine within the past 2 years, if they had received anti-CD20 monoclonal antibody therapy within the past 6 months, were on immunosuppressive therapies including steroids in the past 14 days (maintenance steroids with ≤20 mg/day prednisone equivalent were allowed), had a recent infection requiring systemic treatment in the past 14 days, or had an Eastern Cooperative Oncology Group performance status of 3 or 4.

At day 0 of study enrollment, both study cohorts received a single dose of PCV13. Peripheral blood samples were collected prevaccination on day 0 and on day 30 postvaccination. Serum pneumococcal antibody assessment was performed on day 0 and day 30 by measuring IgG antibodies specific for 12 pneumococcal serotypes (1, 3, 4, 5, 9, 12F, 14, 19F, 23F, 6B, 7F, and 18C) using microsphere photometry. Mononuclear cells were isolated using Ficoll-Histopaque 1077 density gradient centrifugation, and specific CD19+ cells were isolated using Dynabeads CD19 pan B. Western Blot analysis was performed to evaluate BTK and SAMSN1 expression.

Eight patients with CLL were enrolled in this study, 4 in the ibrutinib arm and 4 in the control arm. All the patients in the control arm (4/4) generated an adequate immune response to PCV13 versus none (0/4) of the ibrutinib-treated patients (p = .029). Overall, there was a significant increase in the median change of specific pneumococcal antibody titers in the control group compared to the ibrutinib group (p < .0001; confidence interval [CI] 90–124.7). Dr. Andrick noted an interesting secondary finding of significant elevation in SAMSN1 expression prevaccination in the ibrutinib arm (p < .0115), which he stated “may mechanistically explain the lack of immune response generated following PCV13 vaccination. Higher baseline SAMSN1 expression could be a parallel mechanism by which CD19+ cells attempt to overcome BTK inhibition, which halts proliferation and differentiation secondary to B-cell receptor signaling. The interaction of an adaptor protein such as SAMSN1 on the phosphorylation of BTK is intriguing.”

Prior to this study, the effect of ibrutinib on PCV13 vaccination response was unknown. This pilot study suggests that ibrutinib therapy may attenuate pneumococcal vaccination response. On the basis of these results, Dr. Andrick and colleagues suggest that clinicians consider PCV13 vaccination prior to initiating ibrutinib. However, larger studies should be conducted to provide clear guidance on the clinical implications of vaccinations in patients receiving ibrutinib.