Factors Influencing Incidence of Supraventricular Arrhythmias during and after Autologous Stem Cell Transplant in Multiple Myeloma
Authors: Sturdy Megan , Ye Rebecca , Jenkins Trevor L , Driscoll James , Caimi Paolo , Metheny Leland , Zebrowski Rachel , Ferrari Nicole , Kolk Merle , de Lima Marcos , Malek Ehsan 
Published: October 2019

Abstract
Multiple Myeloma (MM) are often treated with high-dose melphalan and autologous stem cell transplant (ASCT), followed by maintenance therapy (McCarthy et al. JCO, 2017). Cardiac toxicity is a potentially serious complication and is a dose limiting toxicity of high-dose melphalan. Furthermore, the overall risk of cardiac event is higher in MM patients compared to age- and gender-matched individuals without MM (Kistler et al. Clin Lymph, Myel & Leuk, 2016). Pre-transplant cardiac screening may help prevent major cardiac complications such as severe heart failure, cardiac tamponade, or life-threatening cardiac arrhythmias. Supraventricular tachy arrhythmias (SVT) are a common complication which may be related to Melphalan, the transplanted stem cells or effects of para-proteinemia on the conduction system. Here, we sought to determine the incidence of SVT and its predisposing factors in this setting.
Methods: We reviewed the 100-day post-ASCT clinical course of all MM patients treated from 2007 to 2017 that had undergone ASCT at University Hospitals Cleveland Medical Center. Patients also diagnosed with cardiac Light Chain Amyloidosis (AL) were excluded. Clinical data on the following characteristics were collected: patients' demographics, disease characteristics, pre-ASCT comorbidities and cardiovascular-related medication use, electrocardiography (ECG) and echocardiography (ECHO). ECG and ECHO studies was limited to one year prior to ASCT. Presence of left ventricle hypertrophy (LVH), ejection fraction (EF), impaired relaxation or abnormally low QRS voltage on pre-ASCT were recorded. QRS amplitude was measured in the V2 precordial lead as the distance from the R peak to S peak. Both atrial fibrillation and atrial flutter were classified as SVT. Continuous variables were compared using the unpaired t-test, and categorical variables were compared using the two-tailed Fisher's exact test. A multiple logistic regression model was fit to a model containing all the collected potential risk factors. Odds ratios (ORs) and confidence intervals (CIs) were estimated from the estimated betas in the model. A two-tailed p value < 0.05 was considered to be statistically significant.
Results: A total of 222 patients were included in the study population. Amifostine was used before all ASCT to reduced oral mucositis. Patient median age was 60.6 (range: 36-79), 110 patients (49%) were male and the 112 female (51%). Median pre-ASCT QRS amplitude was 1.7 millivolt (mV) (range: 0.3-4.4). Median QRS duration was 90 millisecond (mS, range: 60-208). Only 166 patients received a pre-ASCT ECHO. Median time of pre-ASCT and post-ASCT ECHO were 38 days (range: 1-333 days) and 55 days (range: 4-118), respectively. Seventeen patients (8%) developed SVT during or after ASCT with a median time of 12 days post-ASCT (range: 1-97 days). Median time of the length of hospital stay between patients without SVT and with SVT was different, 15 vs. 19 days (p-value < 0.001). There was no statistically significant between average melphalan dose utilized as the conditioning regimen, infused CD34 dosage, transplant-associated weight loss, time from diagnosis or length of pre-ASCT exposure to proteasome inhibitors between two cohorts (Table-1 and 2). Also, there was no association between pre-ASCT use of anti-lipid lowering agents, beta-blockers, angiotensin-converting enzyme inhibitor or angiotensin receptor inhibitors. Out of all pre-ASCT comorbidities renal insufficiency (9% vs. 41%, p-value: 0.017) and HTN (49% vs. 76%, p-value: 0.045) were predictor, of SVT occurrence in the univariate analysis. Multivariate analysis indicated that renal insufficiency at baseline (OR: 3.6, 95% CI: 2.1-4.8, p-value < 0.001), left ventricular systolic dysfunction (LVSD, OR: 3.0, CI: 1.1-5.1, p-value: 0.003), and hypertension (OR: 2.5, CI: 1.2-4.6, p-value: 0.028), were significantly associated with the development of SVT after ASCT (Fig. 1).
Conclusion: Taken together, our results suggest that SVT represents an important cause of morbidity and is associated with longer hospital stay for MM patients undergoing ASCT. The presence of abnormal renal function, LVSD, or hypertension at baseline identifies patients at greater risk of developing SVT following ASCT. Further studies are warranted to establish robust risk models that may predict SVT in MM patients prior to and during ASCT.

Disclosures
Caimi: ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Malek:Takeda: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.