ALBERT

Description: Background We have a poor understanding of the vaccination immune response and outcomes in multiple myeloma (MM). As MM patients (Pts) are living longer and therapies are immunomodulatory there is an unmet medical need to further characterize the role of the immune system. A common reason for hospitalization or death in MM Pts is infection. As an initial step in MM Cancer Care Delivery Research (CCDR), we evaluated the current vaccination practice patterns in MM Pts at Aurora Health Care using the EMR and data analytics. Methods An IRB approved study reviewed MM Pts from 5/15/2012 to 5/15/2014. Data collected included demographics, influenza (FV) and pneumonia vaccination (PV) history, hospitalization episodes, cost associated with hospitalization, and admission and discharge diagnoses. Pts were considered PV positive if vaccinated within 5 years prior to study with any PV type. FV was none (no FV in 2012-2014), optimal [FV in 2012 and (2013 or 2014)], or suboptimal [FV in 2012 or (2013 or 2014)]. Data was analyzed using SAS and STATA 12. Results A total of 1131 MM Pts were identified. Race included 70% white, 13% black, and 17% mixed, other or information not available. MM median age at diagnosis was 71 and only 4% (47) had prior autologous stem cell transplantation. PV rate was 30%. FV was 55% none, 24% suboptimal and 20% optimal. There was no statistically significant difference in the rate of PV and FV when stratified vs age, gender, and race. Over two years there were a total of 662 hospitalization events involving 317 MM Pts. The total cost of hospitalization was approx $35M. The average charge per hospitalized patient was $110K (range: $2K -1.3M) with an average $52K per hospitalization encounter (range: 2K – 648K). The rate of PV and FV vaccination among Pts with index hospitalization is significantly higher than non-hospitalized patients. There was no difference in hospitalization cost based on vaccination status. (See Table 1) Discussion Vaccination rates were low and did not correlate with hospital outcomes. This may be explained as a limitation for a retrospective EMR analysis without accounting for temporal relationship of vaccines – i.e. possible vaccination after admission. Alternatively, this may indicate that our current methods of vaccination in MM are not effective. Other limitations include need for a more granular review of treatment regimens and infectious complications. Additional surrogate markers are needed to understand the effect of vaccines and the immune system on health care outcomes such as hospitalizations, cost, and survival. This will be addressed in prospective registries and immunologic studies at our center and may be queried at other health systems. Table 1 – Vaccination Status and Hospitalizations Vaccination Status % Hospitalization Events, % Hospitalization Charge, $ PV – No 70% 20% $16M PV – Yes 30% 52% $18M FV – None 55% 16% $9M FV – Suboptimal 24% 42% $13M FV - Optimal 20% 43% $12M Disclosures No relevant conflicts of interest to declare.

Description: Background Multiple myeloma (MM) is a cancer of the immune system. Infection is a major cause of morbidity and mortality in MM. Vaccinations (vax) are recommended in MM, but clinical efficacy endpoints have not been demonstrated and surrogate markers of efficacy have limited data. This pilot study evaluated sequential immunologic markers after standard vax for pneumococcal pneumonia (PV) and influenza (FV). Methods MM patients and non-MM control (Ctrl) participants signed informed consent to this IRB approved study. The MM patients were not selected for treatment or disease status. Vax was standard PV (PCV13 or PPV23) and/or FV (IIV4) with research laboratory testing at baseline and at 2, 4, 12, 24 weeks after vax. If PV, then PCV13 preferred followed by PPV23 suggested at 〉= 26 weeks. IgG antibodies (Ab) to influenza and pneumococcal antigens were detected by ELISA. Measurement of Ab to influenza was performed as previously described (Oaks et al. 2013OncoImmunology) and used Flulaval Quadrivalent 2015/2016 form (GlaxoSmithKline) as the coating antigen. Anti-pneumococcal IgG levels were determined with The Binding Site VaccZymeAnti-PCP IgG EIA Kit (#MK012-U) according to the manufacturer's instructions. Results Ten MM (5 M, 5 F) and 9 Ctrl (4 M, 5 F) were enrolled. MM median age was 69.8y (range: 59-78) and Ctrl was 63.5y (range: 56-73). Over the total time course 5/10 MM and 4/9 Ctrl had no missing samples. Vax included: 5 (2 MM, 3 Ctrl) FV only; 10 (6 MM, 4 Ctrl) PV (8 PCV13, 2 PPV23) only; and 4 (2 MM, 2 Ctrl) both FV and PV (3 PCV13, 1 PPV23). Tetanus Ab response was unchanged, which served as a negative control. FV results included 2/4 MM showed at least a doubling of anti-flu titer, although the other 2 showed no measurable response. All 5/5 Ctrl had at least a 2-fold increase in anti-flu titers at some point. PV humoral response varied considerably for both MM and Ctrl. All 4 Ctrl responded with at least a 2-fold increase in Ab titer, only 2 Ctrl had a sustained increase in titer at the closing visit. Six of 10 MM had at least a 2-fold Ab increase at some point during the course of the study. Only 2 MM patients showed a sustained increase of anti-PV Ab. Response rate differences were not statistically significant and there was no relationship between responsiveness to FV or PV and initial serum IgG concentration at entry into the study (data not shown). Discussion Study limitations include small sample size, sample dropouts, and heterogeneous population. We are unaware of prior MM vax immunology response time courses. This may be because of the difficulties including PV studies with PCV13-〉PPV23 recommendations and the potential long follow up. FV response may be more amenable to short term follow up. In 2013 Hahn and colleagues showed proof of principle with "Boost vax improves influenza humoral immune response in MM" (ow.ly/sEBEO), but without a time course or clinical outcomes data. The 2015Branagan et al. (http://ow.ly/W4tLS) pilot study showed a 2 dose FV strategy had lower flu infections compared to historical controls. Karlsson et al. (http://ow.ly/YUumy) showed that Ab response does not correlate with functional assays. We found no relationship with total IgG level. This is consistent with Beers et al. findings that IgG isotypes may be of more importance than the total IgG level. (http://ow.ly/Z5g2A) Conclusion We found that FV and PV Ab response was low and not sustained in most MM patients. Infection in MM remains an important concern. Future vax studies should address the following: 1) Homogeneous population - eg therapy trial or autologous stem cell transplant with a standardized re-vax and sequential testing, 2) validate relevant immunologic surrogates - eg Ab response twice baseline, 4) fresh assay vs frozen (batched), 5) correlation of metric with functional outcomes such as hospitalization, cost, and death, 6) and epidemiologic data may complement translational approaches. Funding Funding was provided by a Vince Lombardi Cancer Foundation Aurora Cancer Research Award. Responses to FV Table Table. Disclosures Thompson: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: MDS/AML Registry; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AIM Specialty Health: Membership on an entity's Board of Directors or advisory committees; VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Multiple Myeloma International Registry; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.