ALBERT

Description: Background: The discovery that gut microbial dysbiosis correlated with prognosis, immune reconstitution and development of graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplantation (allo-SCT) highlights the clinical relevance of the gut microbiome in shaping anti-tumor immune responses. Treatment of allo-SCT patients with antibiotics has recently been associated with increased GVHD mortality (Routy et al. 2017). Based on these studies and the association of distinct gut bacteria with increased efficacy to PD-1 blockade in patients with solid tumors (Derosa et al. 2018), we performed a retrospective analysis to determine if infection treated with antibiotics affected the outcomes of multiple myeloma (MM) patients after autologous SCT (ASCT). Methods: A list of all MM patients treated at our institution between January 2012 through December 2015 was obtained and 1095 patients were identified. A comprehensive review of the electronic medical record (EMR) of the first 142 who received ASCT was performed. Information was collected from diagnosis to the date of last contact. Baseline characteristics, treatment history, transplant course, antibiotic treatment, and infection severity using common terminology criteria for adverse event (CTCAE) version 4 were reviewed. Prophylactic antibiotics were excluded. Response was measured and defined using the International Myeloma Working Group Criteria. Progression free survival (PFS) and overall survival (OS) were estimated using log rank tests. Cox hazard stepwise regression model examined for multiple factors affecting PFS and OS using the Akaike information criterion. Results: Of the 142 patients, 93 (65%) were Durie Salmon (DS) III, 20 (14%) were Revised International Staging System (R-ISS) III, 44 (31%) had high-risk cytogenetics, and 76 (54%) were male. The median age at diagnosis was 60. Although there was a similar frequency of DS III (67% vs 61%) and high-risk cytogenetics (35% vs 25%) among patients in the antibiotic and non-antibiotic treated groups, there was an over-representation of R-ISS 3 (19% v 4%) patients in the antibiotic-treated group. Treatment with antibiotics was associated with decreased median PFS (2.38 vs 6.58 years (yrs), p =0.00003) (Figure 1a) and decreased median OS (7.43 vs 17.39 yrs, p =

Description: Introduction: In the ASPIRE and ENDEAVOR trials, multiple myeloma (MM) patients treated with carfilzomib (K) had significantly improved progression‐free survival and overall survival compared with standard of care. The incidence of all-grade adverse cardiovascular events (ACVE) was 26.6% and 24.5% in the K treated groups in ASPIRE and ENDEAVOR respectively. The atherosclerotic cardiovascular disease (ASCVD) score is a risk stratification tool used by cardiologists to classify patients with a score ≥7.5% as high risk for the incidence of ASCVD events. To date, there are no clinically relevant models that predict the likelihood of ACVE in MM patients treated with K nor are we aware of any protective factors against ACVE. Our study aims to identify factors which can predict and mitigate the incidence of ACVE. Methods: A retrospective chart review of 372 MM patients who were treated with K between 2011 and 2018 at our institution was performed.Data were summarized using descriptive statistics; Chi-square tests of association and Kruskal-Wallis tests were employed to test for differences across groups, where appropriate. Logistic regression was performed to examine the risk factors associated with ACVE. Results: Of the 372 patients, 243 (65%) were Durie-Salmon Stage (DSS) III, 70 (19%) were International Staging System (ISS) III; 186 (50%) were men. There were a total of 102 (27%) ACVE and 33 (9%) ≥grade 3 events. The most common ACVE were congestive heart failure (29%), asymptomatic elevations in pulmonary arterial systolic pressure (PASP) (27%), and hypertension (HTN) (16%). Sixty-eight (66%) Caucasians, 14 (14%) African Americans and 17 (17%) Hispanics developed ACVE. Aspirin (ASA) (64%), beta blockers (BB) (51%), calcium channel blockers (CCB) (43%) and statins (37%) were the most common cardiac medications patients were taking at the time of K initiation. Regardless of cardiac history, patients who were taking a CCB had higher odds of experiencing an ACVE compared to patients who were not taking a CCB (CCB + Cardiac history: OR=1.9; CI=1.0-3.7; CCB, no Cardiac history: OR=6.3; CI= 2.1-18.4) (Table 1). Patients with an ASCVD score ≥7.5% did not have an increased incidence of ACVE but did have an increased incidence of ≥grade 3 vs. grade 1-2 ACVE (100% vs. 78%, p=0.092). Prior cardiac history, including history of HTN, was common (59%) but not associated with incidence or severity of ACVE. Those with type 2 diabetes had a higher rate of ≥grade 3 vs. grade 1-2 ACVE (33% vs. 10%, p=0.004). Patients on certain CV medications while receiving K-based treatment had a higher incidence of ACVE compared to those not on these medications, including BB (51% vs. 34%, p=0.002), CCB (43% vs. 26%, p=0.002), aldosterone antagonists (AA) (8% vs. 3%, p=0.024) and statins (37% vs. 25%, p=0.022). Patients on ASA were more likely to experience ≥grade 3 compared to grade 1-2 ACVE (78% vs. 53%, p=0.016). ACE inhibitors or angiotensin receptor blockers (ACE/ARB) were not associated with increased incidence or severity of ACVE. The use of K in relapsed, as opposed to induction setting, was associated with a higher incidence of ACVE (31% vs. 20%, p=0.035). Maximum dose and number of K doses were not associated with ACVE. There was no relationship between PASP elevation and age 〉75, use of BB, CCB, AA, ACE/ARB, number of K treatments or maximum dose of K. Factors that were associated with increased odds of ACVE in multivariate analysis included patients who received K in the relapsed setting (OR= 1.7; CI=0.94-3.0) and use of an AA (OR= 4.5; CI=1.4-14.1) (Table 1). Conclusion: In line with prior studies, 28% of MM patients treated with K at our institution developed an ACVE, with 9% grade 3 or above. Use of CCB and AA were particularly associated with increased risk of ACVE, while use of ACE/ARB were not. ASCVD score ≥7.5% was associated with an increased incidence of ≥grade 3 ACVE in K-treated patients and should perhaps be evaluated as a predictive tool in prospective studies. Disclosures Siegel: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Speakers Bureau. Biran:Merck: Research Funding; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; BMS: Research Funding.