Efficacy and Safety of Metformin Use in Rheumatoid Arthritis: A Randomized Controlled Study

Objective: To evaluate the efficacy and safety of metformin use in rheumatoid arthritis (RA) patients receiving conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs).Methods: A prospective, randomized, controlled, single blinded, study was carried on 66 RA patients with moderate and high disease activity state, receiving csDMARDs. Patients were simply randomized to receive either metformin 850 mg twice daily (Metformin group, n = 33), or placebo twice daily (Control group, n = 33) in addition to their stable anti-rheumatic regimen and followed up for 6 months. Serum C-reactive protein (CRP), disease activity of 28 joints based on CRP (DAS-28-CRP), and quality of life (QOL) were evaluated at baseline and then every 3 months. Moreover, serum adiponectin was assessed at baseline and after 6 months.Results: Sixty patients completed the study. Drop out was due to intolerance to metformin side effects (n = 3) and non-compliance (n = 3). Metformin significantly decreased CRP levels and DAS-28-CRP after 6 months compared to the control group (p-value <0.001). A significant improvement in QOL of metformin group was observed as early as after 3 months (p-value = 0.006) with a continued improvement observed at 6 months (p-value <0.001) compared to the control group. Despite the significantly higher serum adiponectin in the metformin group at baseline, it was significantly reduced after 6 months in the metformin group with median percent change of −63.49% compared to the significant increase in the control group with median percent change of 92.40%.Conclusion: Metformin significantly improved inflammation, disease severity, and QOL in RA patients with high safety profile.Clinical Trial Registration: Clinical-Trials.gov, identifier [NCT08363405].

EFFECT OF OZANIMOD ON FECAL CALPROTECTIN AND FECAL LACTOFERRIN, BIOMARKERS OF INTESTINAL INFLAMMATION, IN THE PHASE 2 TOUCHSTONE STUDY OF PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS

Introduction Efficacy and safety of ozanimod, an oral sphingosine-1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, was previously demonstrated in the double-blind phase 2 TOUCHSTONE study (NCT01647516) in patients with moderate-to-severe ulcerative colitis. Here we report the effect of ozanimod on levels of fecal calprotectin (FCP) and fecal lactoferrin (FLF), two markers of intestinal inflammation. Methods Patients in TOUCHSTONE were randomized 1:1:1 to once daily oral ozanimod HCl 0.5 mg (equivalent to ozanimod 0.46 mg), ozanimod HCl 1.0 mg (equivalent to ozanimod 0.92 mg), or placebo for 8 weeks; responders at week 8 (based upon Mayo score) entered a maintenance phase through week 32. Stool collection occurred at baseline and weeks 8 and 32 to measure levels of FCP and FLF. Results A total of 197 patients were randomized and received treatment (n=65, placebo; n=65, ozanimod 0.5 mg; n=67, ozanimod 1 mg). Median baseline levels of FCP were 1272, 1477, and 1238 μg/g, respectively; baseline FCP levels were not associated with baseline Mayo score. Median baseline levels of FLF were 29.0, 30.6, and 29.9 μg/g, respectively; baseline FLF was related to week 8 Mayo score even after adjusting for baseline Mayo score. At week 8, FCP levels declined across treatment groups (median percent change from baseline, -53.4, -68.7, and -70.0 in placebo, ozanimod 0.5 mg and 1 mg groups, respectively); declines in FCP were maintained at week 32 (median percent change from baseline, -42.3, -72.6, and -80.6, respectively). At week 8, declines in FCP were greater in patients achieving clinical response (based on Mayo score) than in non-responders on ozanimod 1 mg. Declines in FCP at week 8 were also greater in patients achieving clinical remission than in those who did not, with greater declines with ozanimod 1 mg relative to 0.5 mg. FLF levels declined at weeks 8 and 32 across treatment groups, with greater changes in the ozanimod 1 mg group vs placebo (median percent change from baseline, week 8: -35.7, -61.0, and -84.7, respectively; week 32: -60.2, -62.5, -85.3, respectively, for placebo, ozanimod 0.5 mg, and ozanimod 1 mg). Reductions in FLF at week 8 were greater for treatment responders vs non-responders and for those achieving vs not achieving clinical remission in the ozanimod 1 mg group. Conclusion In TOUCHSTONE, treatment with ozanimod was associated with declines in FCP levels in treatment responders (for the 1 mg dose group) or those who achieved clinical remission (both doses). Ozanimod 1 mg was also associated with declines in FLF for treatment responders and those achieving remission.

Abstract 220: Public Defibrillator Accessibility and Mobility Trends During the Covid-19 Pandemic in Canada

Introduction: The COVID-19 pandemic has led to widespread closures of non-essential businesses and buildings. The impact of such closures on public automated external defibrillator (AED) accessibility compared to mobility trends is unknown. Methods: We identified all publicly available online AED registries in Canada last updated May 1, 2019 or later. AEDs were classified by location type using addresses and registry notes, and deemed completely inaccessible, partially inaccessible, or unaffected using government-issued closure orders as of May 1, 2020. We mapped AED location types to categories used by Google’s COVID-19 Community Mobility Reports and calculated the median percent change in daily traffic between Feb. 15 - May 1, 2020 (excluding Apr. 10-12). We compared the percent of completely inaccessible AEDs to the median percent change in traffic for each category. Results: We identified three provincial (British Columbia, Alberta, Nova Scotia) and two municipal (Mississauga and Toronto in Ontario) online AED registries, collectively covering 13.1 million people. Of the 5,845 AEDs identified, 69.9% were completely inaccessible, 18.8% were partially inaccessible, and 11.3% were unaffected. AEDs in parks (n=141), almost all retail and recreational locations (n=1,539), and two-thirds of workplaces (n=3,633) were completely inaccessible, grocery and pharmacy-based (n=173) AEDs were partially inaccessible, and transit station (n=277) and residential (n=85) AEDs were unaffected. The largest discrepancies between AED accessibility and mobility occurred in parks (100% completely inaccessible vs. 10.5% traffic decrease), retail and recreation (99.0% completely inaccessible vs. 48.0% traffic decrease), and transit stations (100% unaffected vs. 63.0% traffic decrease). Conclusion: Government-mandated closures due to the COVID-19 pandemic have led to a greater reduction in AED accessibility than mobility in many locations across Canada.

Interpreting Anion Gap Values in Adult and Pediatric Patients: Examining the Reference Interval

Background The anion gap is primarily used in the diagnosis of acid-base disorders. We conducted a study to determine the anion gap reference interval in our patient population, investigated the workup of abnormal vs normal anion gaps, and examined the anion gap variation upon repeated testing. Methods A retrospective review was performed on 17137 adult and pediatric patients who presented to Yale-New Haven Hospital outpatient clinics, emergency department, or intensive care units between 2012 and 2017. Results We derived a new reference interval of 7 to 18 mmol/L with a median of 13 mmol/L in healthy adults with no significant differences owing to partitioning by sex or age. Based on the new reference interval, 5%, 23%, and 18% of healthy, emergency department, and intensive care unit adult patients, respectively, were misclassified as having high values with the previous interval of 6 to 16 mmol/L. However, there were no significant differences in the number of tests ordered in patients with anion gaps above and below the upper limit of the previous reference interval. The majority of increased anion gaps that were repeated normalized by 12 h. In a subgroup of healthy adult patients with annual testing, the median percent change in each patient's anion gap from 2015 to 2016 was approximately 13%. Conclusions The anion gap should be used with an appropriate reference interval to avoid misclassification. There may be a moderate degree of individuality that argues for comparing the anion gap with its baseline value in the same patient pending further studies that formally derive its biological variation.

P5326Effect of evolocumab on lipoprotein(a) levels: results across 15 studies

Background/Introduction Elevated levels of lipoprotein(a) (Lp[a]) have been associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Elevated Lp(a) is relatively refractory to lifestyle change and pharmacologic intervention. Purpose To examine the effect of evolocumab on Lp(a) in a range of clinical trial populations, including hypercholesterolaemia/mixed dyslipidaemia, statin-intolerance, diabetes mellitus, and heterozygous familial hypercholesterolaemia (HeFH) at different timepoints up to 5 years. Methods Fifteen phase 2 and phase 3 double-blind and open-label extension studies, with a minimum 12 weeks duration that used approved doses of evolocumab (140 mg every 2 weeks [Q2W] or 420 mg once monthly [QM]) were included in this analysis. Studies were pooled on the basis of patient population, duration, and comparator groups (of which the MENDEL-1, -2, GAUSS-1, -2, and LAPLACE-2 atorvastatin cohort studies employed ezetimibe comparators). The effect of evolocumab on percent change from baseline in Lp(a) was examined. Results In short-term studies, evolocumab led to a median percent change in Lp(a) from baseline to week 12 of −21.2% to −33.3% overall (Table). Results were similar for both evolocumab doses with median percent change ranging from −22.0% to −38.2% for 140 mg Q2W and −20.0% to −33.3% for 420 mg QM. In long-term studies (1 to 5 years), percent change in Lp(a) ranged from −23.8% to −33.3%. Patient populations Percent change from baseline in Lp(a), median (Q1, Q3), % Ezetimibe comparator trials Placebo comparator trials Evolocumab Ezetimibe Evolocumab Placebo 12-week studies Hypercholesterolaemia/mixed dyslipidaemia (YUKAWA-1, -2, LAPLACE-TIMI-57, LAPLACE-2, MENDEL-1, -2) −22.0 (−39.4, 0.0), n=760 0.0 (−11.8, 14.6), n=387 −26.3 (−44.7, −5.0), n=1838 0.0 (−10.4, 15.4), n=1179 Statin intolerance (GAUSS-1, -2) −23.1 (−42.0, −3.3), n=223 0.0 (−16.7, 3.6), n=126 – – HeFH (RUTHERFORD-1, -2) – – −21.2 (−38.1, −7.0), n=263 0.0 (−4.2, 15.3), n=150 Type 2 diabetes (BANTING, BERSON) – – −33.3 (−55.6, −16.7), n=833 0.0 (−16.2, 16.7), n=425 Long-term studies 1-Year (DESCARTES) – – −28.4 (−49.2, −6.0), n=535 −5.5 (−20.5, 0.9), n=272 2-Year (OSLER-2)†‡ −23.8 (−44.4, 0.0), n=3077 – – – 5-Year (OSLER-1)† −33.3 (−51.3, −11.1), n=941 – – – †All patients received evolocumab in the OSLER studies. ‡OSLER-2 was a 3-year study; however, only 2-year data were available for Lp(a). Conclusion Evolocumab reduces Lp(a) in a variety of patient populations at 12 weeks with sustained lowering over 5 years. Acknowledgement/Funding Amgen Inc.

1288. Bone Safety Outcomes with F/TAF vs. F/TDF for PrEP in the DISCOVER Trial

Background In the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here we report the bone safety outcomes of F/TAF and F/TDF. Methods Men who have sex with men (MSM) and transgender women (TGW) at risk of HIV were randomized 1:1 to receive blinded F/TDF or F/TAF, taken once daily. Those on PrEP with F/TDF were eligible to enroll. Bone densitometry (DXA) of the hip and spine were performed in a subset of participants (BMD subset). Fracture events were compared in all study participants. Week 48 data are presented. Results 5387 participants were enrolled in the main study, with 383 included in the BMD subset. In the BMD subset, the median age was 37 (IQR 29, 46); 0.8% were TGW, 9.4% were black, and 20.6% were Hispanic or Latinx. Fifty-three BMD subset participants were on baseline F/TDF PrEP at enrollment, 26 of whom were randomized to F/TAF. F/TAF was associated with more favorable changes in hip and spine BMD compared with F/TDF (Table 1); these differences were similar when participants on baseline PrEP were excluded. Participants age <35 on F/TAF gained BMD, whereas those on F/TDF lost BMD (Table 1). BMD decreases of ≥3% were less frequent in the F/TAF group than the F/TDF group at the hip (3.8% vs. 18.4%, P < 0.001) and spine (10.1% vs. 26.9%, P < 0.001). Osteopenia was more frequently diagnosed in the spine in participants on F/TDF compared with F/TAF (Figure 1, P = 0.007); but not in the hip. Fracture event frequency was the same (53 [2.0%] per group, P = 1.00). One pathological fracture was reported in the F/TAF group compared with two in the F/TDF group (P = 0.57). In participants on baseline F/TDF PrEP, those randomized to F/TAF had significantly improved hip BMD compared with baseline (median percent change 1.13 [IQR −0.86, 3.47], P = 0.027), while spine BMD was unchanged. Conclusion Through 48 weeks, DXA subset participants taking F/TAF for PrEP had significantly less change in BMD than those taking F/TDF, and were less likely to develop spine osteopenia. The incidence of fracture was similar, and pathological fractures were rare. F/TAF for PrEP is effective and has a superior bone safety profile compared with F/TDF. Disclosures All authors: No reported disclosures.

A Phase 2 Study of the Safety and Efficacy of INCB050465, a Selective PI3Kδ Inhibitor, in Combination with Ruxolitinib in Patients with Myelofibrosis

Introduction: Despite the demonstrated efficacy of ruxolitinib (Rux) in patients (pts) with myelofibrosis (MF), suboptimal or declining responses to Rux occur, possibly due to persistent PI3K/AKT activation with chronic JAK inhibitor therapy. We evaluated the combination of INCB050465, a potent and highly selective PI3Kδ inhibitor (≥19,000-fold selectivity for PI3Kδ vs other isoforms) and Rux in pts with MF with suboptimal response to chronic Rux monotherapy. Methods: Pts with primary, post-polycythemia vera or post-essential thrombocythemia MF with suboptimal response or loss of response (palpable spleen >10 cm below left subcostal margin [LSM], or splenomegaly 5-10 cm below LSM and presence of 1 symptom score ≥5 or 2 symptom scores ≥3 using the Screening Symptom Form) after ≥6 months of Rux monotherapy (5-25 mg twice daily, stable dose for ≥8 weeks [wks]), and ECOG performance status ≤2 were eligible for this phase 2 study (NCT02718300). All pts in Part 1 (safety run-in) and Part 2 (expansion) received oral INCB050465 once-daily (QD) for 8 wks followed by once-weekly (QW) at the same dose plus Rux (existing stable dose for ≥8 wks). Part 1 assessed up to 3 dose levels of INCB050465 (5, 10, and 20 mg). In Part 2, pts were randomized to treatment groups (TGs) in a 1:1 ratio between two doses of INCB050465 determined in Part 1. Primary endpoints were to identify tolerated INCB050465 dose in combination with Rux (Part 1) and percent change in spleen volume from baseline through wk 12 (Part 2). Results: At data cutoff (May 01, 2018), 10 and 18 pts were enrolled in Parts 1 and 2, respectively. INCB050465 doses of 10 mg (TG10, n=3) followed by 20 mg (TG20, n=7) were explored in Part 1. No DLTs were observed, thus the 5 mg dose was not assessed, and the 10 mg (TG10, n=11) and 20 mg (TG20, n=7) doses were expanded in Part 2. In Part 1 (n=10) (median age, 69 years [60-79]; males, 60%), median spleen volume (cm3) was 3058 (996-5324) at baseline. Five pts (50%) discontinued treatment due to progressive disease (n=1, TG10), physician decision (n=1; TG20), adverse event (AE; n=1; TG20, blood bilirubin increased), consent withdrawal (n=1; TG10), and decision to proceed to transplant (n=1; TG10). Median percent change in spleen volume was +4.3% and -2.0% at wks 12 and 24, respectively (Figure). By wk 16, 40% of pts reported that their MF-related symptoms were much improved on the Patient Global Impression of Change (PGIC) form. In Part 2 (n=18) (median age, 63.5 years [41-89]; males, 38.9%), median spleen volume (cm3) was 2201 (327-3569) and median total symptom score (TSS; by the Myeloproliferative Neoplasms Symptom Assessment Form [MPN-SAF]) was 30 (3-61) at baseline. One pt in TG20 discontinued treatment due to physician decision. Median percent change in spleen volume was -0.3% and -5.2% at wks 12 and 24, respectively (Figure). By wk 16, 33.3% of pts reported that their MF-related symptoms were much or very much improved on the PGIC. Median percent change in TSS by the MPN-SAF was -21.9% and -27.8% at wks 12 and 24, respectively. MPN-SAF TSS was a planned longitudinal endpoint only for Part 2 and updated data for Part 2 pts will be presented. In both Parts 1 and 2, nonhematologic treatment-emergent AEs (TEAEs) occurring in ≥3 pts were primarily grade (Gr) 1/2 (Table). Most common new or worsening Gr 3/4 hematologic AEs were thrombocytopenia (Gr 3: 4 pts [14.3%]; Gr 4: 4 pts [14.3%]) and neutropenia (Gr 3: 2 pts [7.1%]; both pts had Gr 2 neutropenia at baseline). No serious TEAEs of interest were reported. TEAEs led to INCB050465 dose interruption in 11 pts (thrombocytopenia [n=8 events], pyrexia [n=2 events], and abdominal pain, diarrhea, alanine aminotransferase increased, and aspartate aminotransferase increased [n=1 event each]), and to Rux dose interruption in 3 pts (pyrexia [n=2 events] and thrombocytopenia [n=1 event]). Conclusion: The add-on strategy of INCB050465 plus Rux demonstrated preliminary efficacy in MF pts with suboptimal spleen and/or symptom response to chronic Rux monotherapy. The dosing regimen (QD for 8 wks followed by QW) of INCB050465 in this study seemed to mitigate AEs observed with other PI3K inhibitors (limited Gr 3/4 TEAEs and no TEAEs of colitis or rash reported). Long term dosing strategies will be explored in Part 3 of the study, and additional trials are underway to identify optimal dosing of INCB050465 for enhanced safety and efficacy in combination with other agents. Disclosures Daver: Karyopharm: Research Funding; Novartis: Consultancy; Alexion: Consultancy; Karyopharm: Consultancy; Otsuka: Consultancy; ImmunoGen: Consultancy; ARIAD: Research Funding; Sunesis: Consultancy; BMS: Research Funding; Incyte: Consultancy; Pfizer: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Sunesis: Research Funding; Daiichi-Sankyo: Research Funding; Kiromic: Research Funding; Pfizer: Consultancy. Kremyanskaya:Incyte: Research Funding. O'Connell:Incyte: Research Funding. Dao:Incyte: Consultancy. Oh:Takeda: Research Funding; Janssen: Research Funding; CTI Biopharma: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Verstovsek:Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Erickson-Viitanen:Incyte: Employment, Equity Ownership. Zhou:Incyte: Employment, Equity Ownership. Assad:Incyte Corporation: Employment, Equity Ownership. Yacoub:Seattle Genetics: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Novartis: Speakers Bureau.

ADJUNCTIVE PERAMPANEL RCT FOR PGTC SEIZURES

We assessed efficacy and safety of perampanel (selective noncompetitive AMPA receptor antagonist) for primary generalised tonic-clonic (PGTC) seizures. Patients ≥12years with confirmed IGE; ≥3 PGTC seizures/8 weeks prior to randomization; receiving 1–3 concomitant AEDs were recruited. Trial consisted of 4–week screening; 4–8 week Baseline, 1:1 Randomization (perampanel titrated over 4 weeks to 8mg or highest tolerated dose versus placebo), 13–week Maintenance, 4–week Follow-up and Extension Phases. 164 patients were randomized; full analysis set included 81 patients each on perampanel and placebo. Median percent change in PGTC seizure frequency/28 days during Titration/Maintenance versus Baseline was –76.5% with perampanel versus –38.4% placebo; P<0.0001. 50% PGTC seizure responder rate was 64.2% with perampanel versus 39.5% placebo; P=0.0019. During Maintenance, 30.9% of perampanel patients were free of PGTC seizures versus 12.3% placebo. Treatment-emergent AEs (TEAEs) occurred in 82.7% of perampanel and 72.0% placebo patients; most common dizziness, fatigue, headache, somnolence, irritability. Serious TEAEs occurred in 6 (7.4%) perampanel and 7 (8.5%) placebo patients (one death in the perampanel group [accidental drowning; not treatment-related],one with placebo). In conclusion, adjunctive perampanel treatment up to 8mg improved seizure control in PGTC seizure patients, with almost 1/3 free of PGTC seizures during Maintenance. Perampanel was well tolerated. Study sponsor: Eisai Inc.

T-Cell p16INK4A Expression Increases Post-Transplant in Patients with Multiple Myeloma

Multiple myeloma (MM) is an incurable hematologic malignancy primarily of older adults. MM treatment decisions are based partially upon chronologic age, a measure that may not reflect the patients’ physiologic age or ability to tolerate therapy. Recently, investigators have established methodology to better quantify biologic age using the molecular marker, p16INK4a (p16). p16 expression is a marker of cellular senescence and is strongly associated with gerontogenic models. p16 rises exponentially with chronologic aging and is influenced by external factors such as physical activity, tobacco use, and solid tumor chemotherapy. Additionally, single nucleotide polymorphisms located near the p16-encoding INK4/ARF locus are linked to age-related diseases (e.g. cardiovascular disease, diabetes, glaucoma) and decreased physical function. p16 mRNA can be measured in peripheral blood T-cells thus providing a practical means of quantifying this molecular marker of age. To determine the effects of MM therapy and autologous hematopoietic stem cell transplant (AHSCT) on biologic aging, we serially measured T-cell p16 expression in MM cohorts and aged matched controls. Methods: 23 MM patients were divided into cohorts of newly diagnosed (ND; n=11) and prior treatment (T; n=12). T-cell isolation was performed using techniques described by Liu and colleagues (Liu et al. Aging Cell 2009); p16 expression was measured using quantitative RT-PCR. 16 MM patients underwent sequential testing, with a median 42 days between each measurement. During this time, 8 patients had no intervention and 8 received immune modulatory (IMiD) therapy. Healthy age matched control T-cells were analyzed for comparison (n=17). Results: MM patients with a median age of 62 were evaluated; 12 with early stage ISS disease, 21 with an ECOG performance status of 0-1, and 6 with high risk FISH abnormalities. 12 MM patients had prior treatment, most included AHSCT (n=11). MM treated patients had several lines of therapy; half with 1-2 lines and half with 3+ lines. Median time from AHSCT to p16 analysis was 1003 days (range 49-3630) and transplant date was unrelated to p16 expression (p=0.9577). The healthy control median age was 60 (SD 11.77) with a range of 35-82 years. T-cell yield among MM patients and healthy controls was not significantly different. Using univariate linear regression, age correlates significantly with p16 expression in healthy controls (p=0.0039) wherein p16 is estimated to increase by 1.035 fold each year [0.05 Cts per year]. Using multivariable regression analysis, age and MM status (ND and T), were both independently associated with p16 expression. When controlling for age, patients previously treated for MM had p16 expression that was ~3.68-fold higher than healthy controls (p=0.0003). There was no significant difference in p16 expression between ND MM patients and healthy controls (fold-change=1.15, p=0.70). MM p16 levels were significantly higher in patients with prior therapy (p=0.0439) and for those who had underwent AHSCT (p=0.0129). However, p16 was unrelated to other clinical factors such as cardiovascular disease, tobacco use, radiation, stage, absolute lymphocyte count, or renal function. 8 MM patients where p16 expression was measured pre and post-IMiD treatment, a significant change in expression was not observed (median percent change: 1.16%, p=0.11); in another 8 MM patients who were untreated, p16 levels were also unchanged over time (median percent change: -0.91%, p=0.38). Conclusions: AHSCT significantly impacts p16 expression in T-cells from MM patients. Specifically, MM patients post-AHSCT show a 3.68 fold increase in p16 expression compared to age-matched controls. Time from transplant to assessment does not impact p16 measurements, suggesting that cellular senescence of the T-cell compartment following AHSCT is persistent. MM patients exhibit known T-cell defects including variable T-cell frequency, abnormal signal transduction, and impaired cytokine secretion. Moreover, MM AHSCT patients also show impaired immune reconstitution with changes in T-cell frequency and function. To our knowledge, this is the first report describing cellular senescence post-transplant. Health status and function are affected by AHSCT; our work is important in understanding how biologic markers of age change with intensive therapy, such as AHSCT, to better predict outcomes in future studies. Disclosures Hofmeister: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Honoraria, Research Funding; ARNO Therapeutics: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees.