Citations

Abstract Activated B cell (ABC) type diffuse large B cell lymphoma (DLBCL), double hit lymphoma (DHL) and double expressor lymphoma (DEL) have poor outcomes to frontline R‐CHOP but impact of these molecular features on outcomes of relapsed/refractory (R/R) disease is not well‐characterized. We evaluated the association of diagnostic cell of origin (COO), double hit and double expressor status with overall survival after first relapse in DLBCL patients who were enrolled into the Molecular Epidemiology Resource (MER) cohort. COO was available from immunohistochemistry (IHC) using Hans criteria or gene expression profiling (GEP) (Nanostring) on the diagnostic FFPE biopsy. Of 373 pts with R/R DLBCL, 278 had COO by IHC: 152 were GCB, 107 were non‐GCB. One hundred and fourty had COO by GEP: 44 were ABC, 65 were GCB and 13 were unclassifiable. Nineteen out of 163 (12%) were DHL; 30 out of 135 (22%) had DEL. COO, either by IHC (2 years OS GCB: 45% [CI 95 : 38–54] vs. non‐GCB: 44% [CI 95 :36–55], p > 0.05) or GEP (2 years OS ABC: 42% [CI 95 : 29–59] vs. GCB: 40% [CI 95 : 30–54], p > 0.05), was not associated with difference in OS. DHL (2 years OS 16 [CI 95 :6–45] vs. 45% [CI 95 : 34–59], p < 0.01) and DEL (2 years OS 33% [CI 95 : 20–56], vs. 50% [CI 95 : 41–60], p < 0.05) had lower OS than non‐DHL and non‐DEL/non‐DHL counterparts, respectively. COO by IHC or GEP was not associated with OS in R/R DLBCL while DHL and DEL were adverse prognostic markers in DLBCL at first relapse.

AbstractDirect comparisons of the effectiveness of the numerous novel therapies in the diffuse large B‐cell lymphoma (DLBCL) treatment landscape in a range of head‐to‐head randomized phase 3 trials would be time‐consuming and costly. Comparative effectiveness studies using real‐world data (RWD) represent a complementary approach. Recently, several studies of relapsed/refractory (R/R) DLBCL have used RWD to create observational cohorts to compare patient outcomes with cohorts derived from single‐arm phase 2 trials. Using propensity score methods to balance clinically and prognostically relevant baseline covariates, closely matched patient‐level cohorts can be generated. By incorporating appropriate measures to assess covariate balance and address potential bias in comparative effectiveness study designs, robust comparative analyses can be performed. Results from such studies have been used to supplement regulatory approval of therapies assessed in single‐arm trials. While RWD studies have a greater susceptibility to bias compared to randomized controlled trials, well‐designed and appropriately analyzed studies can provide complementary real‐world evidence on treatment effectiveness.

Abstract Background Speckle tracking echocardiography (STE) has shown to be a good tool to foresee early myocardial dysfunction in lymphoma patients who receive anthracycline based chemotherapy. Conventional STE such as global longitudinal strain (GLS) is a good predictor of cardiotoxicity in these patients, however, a more in-depth characterization of conventional and comprehensive STE parameters to predict a hard end-point as chemotherapeutic related heart failure (HF) has not been evaluated. Purpose The aim of this prospective study was to evaluate predictability of cancer therapeutic-related clinical HF by conventional and comprehensive STE. Methods We enrolled 269 Hodgkin & non-Hodgkin lymphoma patients who underwent chemotherapy at Mayo Clinic from 2013 through 2021. All patients had an echocardiogram performed at baseline (T0), during chemotherapy (T1) and after (T2). HF was diagnosed by a cardiologist and defined as the first occurrence after the initiation of chemotherapy. Conventional (GLS) and comprehensive strain analyses that included: global circumferential strain (GCS), global radial strain (GRS), global longitudinal early diastolic strain rate (GLSRe), global longitudinal systolic strain rate (GLSRs), global circumferential early diastolic strain rate (GCSRe), global circumferential systolic strain rate (GCSRs), global radial early diastolic strain rate (GRSRe), and global radial systolic strain rate (GRSRs), were performed offline. Logistic regression analyses were used to evaluate the association of 2D and 3D STE measurements with the development of clinical HF. Results Overall, 215 (79.9%) patients had non-Hodgkin lymphoma while 54 (20.1%) had Hodgkin lymphoma. Mean age was 58.4±16.1 years and 64.7% of the patients were males. The most prevalent comorbidities were hypertension (101/37.5%), dyslipidemia (87/32.3%) and diabetes (28/10.4%). HF occurred in 21 (7.8%) patients, including 9 (3.3%) during chemotherapy and 12 (4.5%) after chemotherapy. The best predictors of HF were: i) GLSRe and GCSRs performed at baseline (T0) to predict HF at T1 with an AUC of 0.85 each and p values of 0.0006 and 0.0005 respectively (Table 1); ii) GCSRs and GCS at baseline (T0) to predict HF at T1 or T2 with AUCs of 0.82 (p, &lt;0.0001) and 0.81 (p, 0.0004), respectively. Basic strain (GLS) was able to predict HF when measured at T0 but not when measured at T1. All the AUCs for GLS were below 0.75 (Figure 1). Conclusions To our knowledge this is the first study to evaluate the use of conventional and comprehensive STE to predict a hard end-point as heart failure in patients with lymphoma who received anthracyclines. Comprehensive STE measurements as GLSRs, GLSRe, GCS, GCSRs and GCSRe are better than GLS to predict HF in patients with lymphoma who received anthracycline based chemotherapy. These findings can be crucial for the management of these patients by guiding when to start cardioprotection and/or avoid interruptions of cancer treatment. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Department of cardiovascular diseases, Mayo Clinic, Rochester, MN

Abstract Background Assessing cardiac performance of patients receiving chemotherapy is a cornerstone for adequate cardiovascular care. Mitral annular plane systolic excursion (MAPSE) has been considered as a surrogate for Ejection Fraction (EF). However, little is known about its role in predicting Cardiotoxicity or Heart Failure in Lymphoma patients, as its relationship with Global Longitudinal Strain (GLS) and EF. Purpose Our aims were: i) to evaluate if MAPSE and GLS can predict the development of CT and/or HF in lymphoma patients treated with anthracyclines and ii) to evaluate its correlation with GLS and EF. Methods For this prospective observational study, 325 Hodgkin (HL) & non-Hodgkin (NHL) lymphoma patients (n=325) treated with anthracyclines were recruited from 2013 to 2021 and followed for 1 year. MAPSE by M-mode and GLS by Speckle-Tracking (ST) were measured at baseline (T0), during treatment (T1), and up to 1 year after chemotherapy completion (T2). CT was defined as a decrease in EF by &gt;10% to a value &lt;50% and HF by a cardiologist as the first occurrence after the initiation of anthracyclines. Logistic regression analyses with Receiving operator characteristics (ROC) and Area under the curve (AUC) were performed. Pearson's correlation coefficient was also calculated. A p-value &lt;0.05 was considered statistically significant. Results Two hundred sixty-four patients (81.2%) had NHL and 61 (18.8%) HL. Of these, fifteen (4.6%) and 21 individuals (6.4%) developed CT at T1 and T2, respectively. Nine subjects (2.8%) developed HF at T1 and 14 (4.3%) at T2. MAPSE at T0 had the highest AUC to predict both HF at T1 (AUC=0.865, cut-off 14.9, sensitivity 100%, specificity 63%, p=0.008) and at T2 (AUC=0.757, cut-off 10.9, sensitivity 67%, specificity 93%, p=0.045). This same variable at T1 predicted HF at T2 with an AUC of 0.752 (cut-off 11.4, sensitivity 67%, specificity 94%, p=0.004). For CT prediction at T2, MAPSE at T1 had an AUC of 0.738 (cut-off 12.5, sensitivity 56%, specificity 85%, p&lt;0.0001). GLS at T0 predicted CT at T1 (AUC=0.657, cut-off −19, sensitivity 67%, specificity 63%, p=0.012) and when obtained at T1, it predicted CT at T2 (AUC=0.776, cut-off −17, sensitivity 74%, specificity 75%, p-value &lt;0.0001) (Table 1). Pearson's correlation between MAPSE and GLS at T0 (coefficient −0.25, p=0.023) at T1 (coefficient −0.38, p&lt;0.0001) at T2 (coefficient −0.037, p&lt;0.0001) and MAPSE with EF at T0 (coefficient 0.33, p=0.0002) at T1 (coefficient 0.28, p&lt;0.0001) and T2 (coefficient 0.29, p&lt;0.001). Conclusions To our best knowledge, this is the first time that MAPSE and GLS were compared to predict CT and HF in lymphoma patients receiving anthracycline-based chemotherapy; we have demonstrated that MAPSE measured at T0 was a very good predictor of HF at T1. Either MAPSE or GLS assessment at T0 and T1 were able to predict CT or HF. Future studies could explore the combination of these two variables to predict either CT or HF. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Department of Cardiovascular Medicine. Mayo Clinic, Rochester-MN