scholarly journals Radiomic Phenotypes of High and Low Lesion SUV Components for the Prediction of Refractory Disease in Hodgkin's Lymphoma Patients Treated with ABVD Based Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3996-3996
Author(s):  
Serageldin Kamel ◽  
Li-Wei Chen ◽  
Gregory Ravizzini ◽  
Ho-Feng Chen ◽  
Joo Schmidt ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Research Funding ◽  
Cancer Center ◽  
Refractory Disease ◽  
Advanced Stage ◽  
Pet Ct ◽  
Frontline Therapy ◽  
The Difference ◽  
Pre Treatment ◽  
Single Lesion

Abstract Background: Hodgkin's lymphoma (HL) is a curable malignancy. However, some patients are refractory to frontline therapy. Early prediction of response to frontline therapy could identify patients who may benefit from more intensive therapy. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has an established role in the management of HL. Radiomic features provide a way of quantifying imaging phenotypes and have shown promising results as predictors of outcomes in different lymphomas. Furthermore, great interest has been focused on the heterogeneity of standardized uptake value (SUV) within a single lesion. Since high SUV component (HSc) and low-SUV component (LSc) regions within a single lesion may be associated with different phenotypical characteristics, the radiomic analysis for each regional SUV component may provide a more complete description of lesions. Therefore, we proposed and evaluated new descriptors to quantify the image phenotypes based on HSc and LSc of lesions in HL. Methods: A total of 61 patients with HL of all stages who were seen at MD Anderson Cancer Center between 2016 and 2020 and had analyzable pre-treatment PET/CT were selected. All patients received standard of care ABVD or AVD regimens with or without radiation (Table 1A). Pre-treatment PET/CT scans were analyzed, and HL lesions were semi-automatically segmented using MIM 7 (Cleveland, OH) based on a SUV max threshold of 2.5. Manual edits were made and reviewed by a nuclear medicine physician and a lymphoma specialist. A total of 110 radiomic features were extracted from the segmented lesions in CT and PET using the open-source package of 'PyRadiomics' (Table 1B). Detailed description and algorithms of the extracted radiomics features are available at https://pyradiomics.readthedocs.io/en/latest/features.html. Additionally, each lesion was partitioned into HSc and LSc based on a cutoff value of 3 times the liver SUV mean (Figure A). The ratio of features between SUV components (HSc, LSc) and the lesion area was calculated. Furthermore, the feature difference between HSc and LSc was obtained. The maximum, minimum, average, and standard deviation of the radiomic features within multiple lesions were computed to reveal the distribution of features. A sequential forward feature selection was applied to select the significant features for building a logistic regression model, to predict refractory disease according to Lugano criteria. Two logistic regression models were constructed for early and advanced stage patients. Quantitative measures, namely metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUV max were measured for comparison. The leave-one-out-cross-validation (LOOCV) was applied to yield the receiver-operator-characteristics curve; the area under the curve (AUC) was then computed to evaluate the performance of the proposed model compared to quantitative measurements using DeLong's test. Results: The average of small dependence high gray level emphasis (GLDM) from PET, the difference of major axis length between high- and low- SUV component from PET, and the difference of 10th Percentile (histogram) between high- and low- SUV component from PET were selected for identifying the refractory disease in early stage lesions; the maximum of correlation (GLCM) from PET, SD of small dependence emphasis (GLDM) from PET, and SD of the inverse difference moment normalized (GLCM) from PET were selected for identifying refractory disease in advanced stage lesions. Based on LOOCV, the proposed radiomics model achieved an AUC of 0.93 for refractory disease prediction, which was significantly superior to MTV (AUC, 0.66; P = 0.01), TLG (AUC, 0.64; P = 0.01), and SUV max (AUC, 0.61; P = 0.01) (Figure B) Conclusion: High and low SUV components-based radiomic model of PET/CT was potentially useful for upfront prediction of refractory HL. Validation in a larger cohort using different segmentation methods, inclusion of additional treatment subgroups, comparison to other predictors, and correlation with survival outcomes are underway. Figure 1 Figure 1. Disclosures Ahmed: Seagen: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Research Funding. Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Pinnix: Merck Inc: Research Funding. Wang: Molecular Templates: Research Funding; The First Afflicted Hospital of Zhejiang University: Honoraria; Hebei Cancer Prevention Federation: Honoraria; Bayer Healthcare: Consultancy; Mumbai Hematology Group: Honoraria; Pharmacyclics: Consultancy, Research Funding; BioInvent: Research Funding; Celgene: Research Funding; Physicians Education Resources (PER): Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Scripps: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Dava Oncology: Honoraria; Epizyme: Consultancy, Honoraria; Clinical Care Options: Honoraria; BGICS: Honoraria; CAHON: Honoraria; VelosBio: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; InnoCare: Consultancy, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; Genentech: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; CStone: Consultancy; Newbridge Pharmaceuticals: Honoraria; Juno: Consultancy, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Chinese Medical Association: Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Oncternal: Consultancy, Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; OMI: Honoraria; Moffit Cancer Center: Honoraria; Lilly: Research Funding.

scholarly journals Frontline Therapy with Bendamustine and Rituximab (BR) in Follicular Lymphoma: Prognosis Among Patients with Progression of Disease By 24 Months (POD24) Is Poor with Majority Having Transformed Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2873-2873 ◽  
Author(s):  
Ciara Louise Freeman ◽  
Kerry J Savage ◽  
Diego Villa ◽  
David W. Scott ◽  
Alina S. Gerrie ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Research Funding ◽  
Population Based ◽  
Advanced Stage ◽  
Historical Cohort ◽  
Treatment Toxicity ◽  
Early Progression ◽  
Transformed Lymphoma ◽  
Frontline Therapy

Abstract Background: Bendamustine and rituximab (BR) has been a preferred regimen for frontline therapy of patients (pts) with advanced stage follicular lymphoma (FL) since randomized trials demonstrated both favorable efficacy and toxicity profiles (Rummel et al 2013, Flinn et al 2014). However, the incidence of transformation and outcomes of pts with early progression within 24 months (POD24) after BR remain poorly documented. Since 2013, BR has been the recommended frontline therapy for all pts with advanced stage, symptomatic FL in British Columbia (BC). We report this population-based analysis evaluating outcomes following the introduction of BR, including the incidence of transformation and POD24, compared to a historical cohort of pts treated with frontline RCVP. Methods: The BC Lymphoid Cancer Database was used to identify all FL pts treated with frontline BR prior to April 1st 2018. A period of observation prior to systemic therapy was permitted, but pts were excluded if they received prior radiation or single-agent rituximab. All pts had pathologically confirmed FL grades 1-3A and symptomatic advanced stage disease (Ann-Arbor I/II if too bulky/not amenable to radiation or stage III-IV). Pts were excluded if they were HIV positive or had documented discordant/composite lymphoma. Event-free survival (EFS), overall survival (OS), and time-to-transformation (TTTF) were calculated from the date of initiation of systemic therapy. Early progression (POD24) was defined as relapse or progression, death from lymphoma or treatment toxicity within 24 months of initiation of systemic therapy. Outcomes were compared with a historical cohort of pts treated with frontline RCVP, which was the recommended induction prior to BR. All pts were eligible to receive rituximab maintenance, which is standard of care for responding pts post-induction therapy in BC. Results: A total of 296 BR-treated pts were identified with a median age of 61 years (range 24-86) and baseline characteristics as outlined in Table 1. Only 34 (11%) had been previously observed and 239 (81%) received rituximab maintenance. A historical cohort of 347 RCVP-treated pts was identified, with comparable clinical characteristics but longer duration of follow-up (median 8.4y, range 0.6-12.6). With a median follow-up for living pts of 2.8y (range 0.2-7.6), estimates for 2-y EFS and OS were 85% (95% CI 80-89%) and 92% (95% CI 88-95%), respectively, for BR-treated pts. As expected, use of BR was associated with an improvement in EFS compared with RCVP (2-y EFS 76% [95% CI 71-80%], p=0.001), but no difference in OS with current follow-up. A total of 28 (9%) transformations have occurred in BR-treated pts, 68% of which were documented histologically. Only elevated LDH was associated with increased risk of transformation (p<0.001). Compared with RCVP-treated pts, the incidence of transformation over time appears similar with current follow-up (Figure 1). Post-transformation outcome in BR-treated pts was poor, with 2-y OS 39% (95% CI 18-59). Early progression (POD24) has occurred in 35/296 (12%) of BR-treated pts. The majority of these, 27 (77%), had transformed lymphoma. Five POD24 pts (14%) died of lymphoma or treatment toxicity without documented transformation and 3 (9%) had relapse with FL and are still alive at last follow up. By comparison, POD24 occurred in 77/347 (22%) of RCVP-treated pts: comprising 31 (40%) transformed lymphoma, 27 (35%) died of lymphoma or treatment toxicity without documented transformation and 19 (25%) relapsed with FL and are still alive at last follow up. Outcome in BR-treated pts with POD24 was poor, with post-progression 2y OS 38% (95% CI 20-55%) compared to non-POD24 BR-treated patients (Figure 2). Conclusion: This population-based analysis demonstrates that in the absence of transformation or POD24, pts with advanced stage FL have excellent outcomes after frontline BR. The use of BR has not changed the rate of transformation compared with that seen after frontline RCVP, with limited follow-up. The occurrence of early progression (POD24) may be decreasing following the introduction of BR, but the majority of POD24 pts now have transformed lymphoma. As a consequence, only a small proportion of POD24 pts following BR have FL-only relapse that may be considered for novel approaches specific for FL. A greater impact on outcome for POD24 pts after BR will require early prediction and improved treatment of transformed lymphoma. Disclosures Freeman: Seattle Genetics: Honoraria; Abbvie: Honoraria. Scott:NanoString: Patents & Royalties: Named Inventor on a patent licensed to NanoString Technologies, Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria; Roche: Research Funding. Connors:Merck: Research Funding; Janssen: Research Funding; Bristol Myers-Squibb: Research Funding; Cephalon: Research Funding; NanoString Technologies: Patents & Royalties: Named Inventor on a patent licensed to NanoString Technologies, Research Funding; Bayer Healthcare: Research Funding; Genentech: Research Funding; Lilly: Research Funding; Seattle Genetics: Honoraria, Research Funding; F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding; Takeda: Research Funding; Amgen: Research Funding. Sehn:Karyopharm: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

scholarly journals Use of Metabolic Tumor Volume (MTV) in Patients with Mantle Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5321-5321
Author(s):  
Daniel M Guidot ◽  
Ila Sethi ◽  
Jeffrey Switchenko ◽  
Daniel Lee ◽  
Loretta J. Nastoupil ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Advisory Committees ◽  
Post Transplant ◽  
Deauville Score ◽  
Pet Ct ◽  
Pre Treatment ◽  
Active Disease

Abstract Introduction Positron emission tomography/Computed tomography (PET/CT) imaging is utilized for initial staging and response assessment in aggressive non-Hodgkin lymphoma (NHL) but has been less useful for prognostic assessment. Metabolic tumor volume (MTV) is an objective measure calculated from PET/CT imaging that calculates the volume of active disease burden with demonstrated value in some forms of NHL. In particular, interim MTV has been shown to predict progression-free survival (PFS) in diffuse large B cell lymphoma (Yang et al. Annals of Hematology 2013) and in peripheral T-cell lymphoma (Jung et al. BMC Cancer 2015). We evaluated the prognostic impact of MTV in mantle cell lymphoma (MCL). Methods Patients with MCL who underwent autologous stem cell transplant (ASCT) in first remission at Emory who had available pre-treatment, post-induction/pre-transplant, or post-transplant PET/CT's were included. Basic demographic information and key clinical data were collected for each patient. MIM software was used to calculate MTV for all areas of active disease with a cut-off of SUV 4. Two additional predictors collected were Deauville score and total lesion glycolysis (TLG). Deauville score is a categorical scale from 1-5 assigned by a radiologist to estimate severity of disease frequently used in aggressive NHL and was calculated in all post-treatment studies. Zero was assigned for cases where incidental findings prevented application of the Deauville criteria but final impression was no active disease. TLG is a calculation of the total quantity of FDG consumed by the area of active disease. All images were reviewed by a nuclear medicine physician to assist with MTV/TLG assessment and to determine the Deauville score. Pre-treatment, pre-transplant, and post-transplant MTV were tested as independent predictors of overall survival (OS) and progression-free survival (PFS) using Cox proportional hazards models. Demographic and clinical variables were tested as well as Deauville score and TLG by the same means Results Forty patients with a combined total of 19 pre-treatment, 30 pre-transplant, and 30 post-transplant PET/CT scans were identified. Mean age at diagnosis was 58.9 (range 32-81), and 94.3% had stage III/IV disease. Mean MTV pre-treatment was 268 (range 0-3454). Following induction/pre-transplantation, 26 patients (87%) had MTV of 0 and 22 patients (73%) had Deauville score 0/1. Post-transplantation, 28 patients (93%) had MTV of 0 and 25 patients (83%) had Deauville score 0/1. Among demographic and clinical factors (Table 1 and 2), PFS was significantly associated with splenomegaly (HR = 3.87, p = 0.033), any lymph node >5cm (HR = 5.25, p = 0.003), and any lymph node >10cm (HR = 4.52, p = 0.041). OS was associated with age at diagnosis (HR = 0.88, p = 0.005). No particular cutoff value for pre-treatment MTV was found to define a statistically significant predictor of OS or PFS. Similarly, baseline TLG was not associated with PFS or OS. OS was significantly associated with post-transplant MTV (p = 0.043), post-transplant TLG (p = 0.043), and post-transplant Deauville score (p = 0.006). PFS was significantly associated with post-transplant Deauville score only (p < 0.001). Conclusions Study results give limited evidence that PET/CT images have predictive value for MCL patients post-transplant. MTV and TLG were 0 in 93% of post-transplant images, and Deauville was 0/1 in 83%. Still, post-transplant MTV, TLG, and Deauville score were associated with OS, and Deauville score was associated with PFS. While this study shows potential value in PET/CT images for MCL patients in the post-transplant period, it does not support the use of MTV or TLG over Deauville score. Disclosures Flowers: Millenium/Takeda: Research Funding; Roche: Consultancy, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; TG Therapeutics: Research Funding; Mayo Clinic: Research Funding; ECOG: Research Funding; AbbVie: Research Funding; Genentech: Consultancy, Research Funding; Infinity: Research Funding; Acerta: Research Funding; NIH: Research Funding; Gilead: Consultancy, Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 798-798 ◽  
Author(s):  
Stephen M. Ansell ◽  
Joseph M. Connors ◽  
Steven I. Park ◽  
Megan M. O'Meara ◽  
Anas Younes
Keyword(s):  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Research Funding ◽  
Response Rate ◽  
Objective Response ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Multi Agent ◽  
Frontline Therapy

Abstract Abstract 798 Hodgkin lymphoma (HL) is a lymphoid neoplasm associated with the presence of CD30-positive Hodgkin Reed-Sternberg cells in a background of inflammatory cells. The regimen containing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has become a common standard of care for the frontline treatment of HL. However, although ABVD is curative for the majority of patients with advanced stage HL, up to 30% of patients will require a salvage therapy. Brentuximab vedotin (ADCETRIS®) comprises an anti-CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). This phase 1, open-label, multicenter study was conducted to evaluate the safety of brentuximab vedotin when administered in combination with standard therapy (ABVD) or a modified standard (AVD) (ClinicalTrials.gov NCT01060904). Patients received doses of 0.6, 0.9, or 1.2 mg/kg brentuximab vedotin with standard doses of ABVD or 1.2 mg/kg brentuximab vedotin with AVD, depending upon cohort assignment. The combination regimens were administered on Days 1 and 15 of each 28-day cycle for up to 6 cycles of therapy. Each regimen evaluated a dose limiting toxicity (DLT) period, defined as any Cycle 1 toxicity requiring a delay of ≥ 7 days in standard ABVD or AVD therapy. Determination of antitumor activity was based on investigator assessment of objective response according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). FDG-PET interpretation for Cycle 2 was performed by a central review per Deauville criteria with uptake above liver background considered positive. Data are presented for the 51 patients treated. Six patients received 0.6 mg/kg, 13 received 0.9 mg/kg, and 6 received 1.2 mg/kg with ABVD; 26 patients received 1.2 mg/kg with AVD. Overall, 37 patients were male (73%) and the median age of all patients was 33 years (range, 18–59). At baseline, 45% of all patients had Stage IV HL, 25% had an IPS score ≥4, and all patients with available ECOG status had a score of 0 or 1. No DLT was observed up to 1.2 mg/kg in either regimen. Common AEs (≥20 patients overall) noted in the ABVD and AVD cohorts, respectively, were nausea (76%, 77%), neutropenia (80%, 69%), peripheral sensory neuropathy (72%, 65%), vomiting (60%, 38%), fatigue (44%, 46%), and constipation (48%, 31%). Common ≥Grade 3 AEs (>10% of patients overall) observed in the ABVD and AVD cohorts, respectively, were neutropenia (80%, 65%), anemia (20%, 12%), febrile neutropenia (20%, 8%), and pulmonary toxicity (24%, 0%). In the ABVD cohorts, 11/25 (44%) patients had AEs of pulmonary toxicity, interstitial lung disease, or pneumonitis that led to discontinuation of bleomycin; 2 of these events led to death. Of these 11 patients, 7 completed treatment with AVD and brentuximab vedotin. In general, these events occurred between Cycles 3 and 6. No pulmonary toxicity was observed in the AVD cohort. The incidence of neuropathy was similar between the ABVD (72%) and AVD (73%) regimens; none of these events were ≥Grade 4 in severity. Overall, 7 patients discontinued brentuximab vedotin due to an AE (5 ABVD patients and 2 AVD patients). At Cycle 2, 48 patients were evaluated by FDG-PET by central review; of these, all 22 ABVD and 24/26 AVD patients were PET negative. Of the 51 patients treated, 4 withdrew consent or were lost to follow-up prior to end of treatment (EOT) assessments. The remaining 47 patients had a 96% objective response rate: 21/22 ABVD patients (95%) and 23/25 AVD patients (92%) achieved CR at the end of frontline therapy, 1 AVD patient had PR (with further workup ongoing), 1 ABVD patient died of AEs (hyponatremia and pulmonary toxicity) prior to EOT, and 1 AVD patient had PD. In patients with newly diagnosed HL, the maximum tolerated dose of brentuximab vedotin combined with ABVD or AVD was not reached; no DLT was observed up to 1.2 mg/kg every 2 weeks, the maximum planned dose. The safety profile observed confirmed that brentuximab vedotin can be safely combined with AVD; however, combination with a bleomycin-containing regimen is not recommended due to the incidence of pulmonary toxicity. The very high CR rate seen in this cohort of advanced-stage HL patients compares favorably with historical controls and warrants comparison with standard therapy. A phase 3 study comparing brentuximab vedotin combined with AVD versus ABVD alone is planned. Disclosures: Ansell: Seattle Genetics, Inc.: Research Funding; Celgene Corporation: Consultancy. Off Label Use: Brentuximab vedotin is indicated for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. These indications are based on response rate. There are no data available demonstrating improvement in patient reported outcomes or survival with brentuximab vedotin. Connors:Seattle Genetics, Inc.: Research Funding. Park:Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Research Funding. O'Meara:Seattle Genetics, Inc.: Employment, Equity Ownership. Younes:Seattle Genetics, Inc.: Consultancy, Research Funding; Celgene: Honoraria; Novartis: Honoraria, Research Funding; Affimed: Research Funding; Gilead: Research Funding.

R-Bendamustine Vs R-CHOP As Initial Treatment for Advanced Stage Low Grade Follicular Lymphoma: A Matched-Pair Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3048-3048 ◽  
Author(s):  
Karishma Phansalkar ◽  
Mohamed Amin Ahmed ◽  
Nathan Fowler ◽  
Long Ma ◽  
Mansoor Noorani ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Matched Pair ◽  
Cancer Center ◽  
Low Grade ◽  
Advanced Stage ◽  
First Line ◽  
Matched Pair Analysis ◽  
Pair Analysis

Abstract Introduction: In the randomized phase 3 clinical trial performed by the Study group indolent Lymphoma (STiL) in patients with indolent and mantle cell lymphoma, the complete response (CR) rates and progression-free survival (PFS) were superior with first-line bendamustine plus rituximab (BR) therapy compared with CHOP plus rituximab (R-CHOP) therapy. However, in a second randomized phase 3 clinical trial (the BRIGHT study) also performed in patients with indolent and mantle cell lymphoma, the CR rates were similar between BR and R-CHOP groups and PFS data has not been reported. In both trials, the toxicity profile was better for BR compared with R-CHOP. Here, we report the results of a matched-pair analysis of advanced stage low-grade follicular lymphoma patients treated with first-line BR or R-CHOP at MD Anderson Cancer Center, Houston, Texas. Methods: We reviewed the medical records of all patients (n=74) with stage III or IV grade 1 or 2 follicular lymphoma treated at MD Anderson Cancer Center with first-line BR between January 2009 and December 2013. Each BR patient was paired with a grade 1 or 2 follicular lymphoma patient treated with first-line R-CHOP matched by age, gender, and stage. Patients with histological diagnosis of concurrent diffuse large B-cell lymphoma were excluded. Results: There were no significant differences in most baseline patient characteristics including age, gender, stage, FLIPI 1 and FLIPI 2 risk groups, Ki-67 score, absolute monocyte count, and absolute lymphocyte count (p>0.05). However, more patients in R-CHOP group met GELF criteria compared with BR group (69% vs 47%, p=0.012). Also, more patients in R-CHOP group had SUVmax >10 on baseline FDG PET scan compared with BR group (74% vs 49%, p=0.011). Median number of chemotherapy cycles was 6 for both groups (range, 2-6 for BR and 4-8 for R-CHOP). The CR rates were comparable between the two groups (93% for BR and 91% for R-CHOP, p=0.142). The median follow-up was 24.4 months (range, 2.8-63.2 months) for BR patients and 68.1 months (range, 4.4-149.4 months) for R-CHOP patients. At 24 months, the PFS and overall survival (OS) were comparable between the two groups (PFS and OS of 85% and 94% for BR and 82% and 99% for R-CHOP; log rank p=0.654 for PFS and 0.158 for OS). Conclusions: In this 1:1 matched pair analysis of advanced stage low-grade follicular lymphoma patients treated with first-line BR or R-CHOP, the CR rates, PFS and OS were comparable between the two therapies. However, longer follow-up is required for better comparison of PFS, OS, and long-term toxicities between the two regimens. Disclosures Fanale: Seattle Genetics, Inc.: Consultancy, Honoraria, Other, Research Funding. Wang:Pharmacyclics, Janssen: Honoraria, Research Funding. Westin:Novartis: Research Funding.

scholarly journals Analyzing Patient Characteristics Who Received (DA) EPOCH-R for High Risk Diffuse Large B-Cell Lymphoma: MD Anderson Cancer Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4208-4208 ◽  
Author(s):  
Kristin A. Simar ◽  
Vishwanath Sathyanarayanan ◽  
Amir K Issa ◽  
Mohamed Amin Ahmed ◽  
Mansoor Noorani ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Neutropenic Fever ◽  
Rank Test ◽  
Cancer Center ◽  
P Value ◽  
Outpatient Therapy ◽  
Advisory Committees ◽  
Log Rank Test ◽  
The Difference

Abstract Background: Due to ~50% risk of relapse with standard therapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP), an increasing number of patients with high risk diffuse large B-cell lymphomas (DLBCL) are being treated with dose-adjusted (DA) EPOCH-R (rituximab, etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide). DA-EPOCH-R contains a 96-hour continuous infusion can be delivered either in the inpatient or outpatient setting, via use of ambulatory infusion pumps. Potential advantages of outpatient therapy include reduced inpatient burden for routine chemotherapy, less exposure to resistant bacterial infections, increased patient satisfaction, and reduced cost. The ability to administer outpatient DA-EPOCH-R is dependent on the ability of the healthcare facility to administer the regimen safely while maintaining dose adjustments and schedule. We hypothesize that patients who receive DA-EPOCH-R as an outpatient have similar outcomes and toxicity rates as patients who receive the regimen as an inpatient. We further hypothesize that there is a significant cost benefit for patients to receive DA-EPOCH-R as an outpatient. Methods: This was a retrospective database analysis of newly diagnosed consecutive DLBCL patients ≥ 18 years of age who received DA-EPOCH-R chemotherapy at MD Anderson Cancer Center between 2010 and 2014. Patients with double hit lymphoma defined as having a MYC and BCL2 or BCL6 translocation were excluded due to their aggressive nature. We descriptively analyzed demographic variables in this population including, age, gender, international prognostic index (IPI)) and outcome (overall response rates (ORR), complete response (CR), progression free survival (PFS), overall survival (OS), and hospital admission for neutropenic fever events). Additionally, we evaluated the number of outpatient cycles received in relation to survival outcomes and neutropenic fever events. Statistical analysis was done using Fisher's exact test or Chi-square test to evaluate the association between two categorical variables and Wilcoxon rank sum test was used to evaluate the difference in a continuous variable between patient groups. Kaplan-Meier method was used for time-to-event analysis including overall survival and progression free survival. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Results: A total of 196 patients had data available for analysis, with 138 patients (70.4%) receiving all cycles as an inpatient, while 58 patients (29.6%) received at least 1 outpatient cycle of DA-EPOCH-R (Table 1). Compared with patients who received no outpatient cycle, the patients who received any outpatient therapy were younger, had a lower proportion of high IPI, and experienced fewer episodes of febrile neutropenia. The median OS and PFS for the entire population has not been reached, with a median follow-up time for the censored observations of 2.78 years (range: 0.24 - 8.64 years). The difference in OS between the patients who had any outpatient therapy and no outpatient therapy was not significant by the log-rank test (p-value=0.11). The difference in PFS between the patients who had any outpatient therapy and no outpatient therapy was marginally significant for OS by the log-rank test (p-value=0.07). Our cost analysis for 6 cycles of inpatient DA-EPOCH-R is estimated to be ~$88K, or $14.6K/cycle. The cost savings incurred for chemotherapy only expenses for each outpatient cycle is at least $3.3K/cycle or $19.8K for a total of 6 cycles. Conclusion: DA-EPOCH-R is a highly effective regimen for treating aggressive DLBCL which can be administered in an outpatient setting safely, efficaciously, and in a cost-effective manner without any apparent effect on outcome or rate of admission for neutropenic fever. There can be savings of about of nearly $20K per patient for a 6-cycle course of therapy. In our series, patients who received outpatient therapy were younger and may have had greater social support, which could potentially confound results. This retrospective analysis supports the use of outpatient DA-EPOCH-R, but additional studies are warranted to evaluate which patients may benefit most. Disclosures Oki: Novartis: Research Funding. Nastoupil:Janssen: Other: Travel, Accommodations, Expenses, Research Funding; TG Therapeutics: Research Funding; Celgene: Honoraria; AbbVie: Research Funding. Fowler:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Wang:Asana BioSciences: Research Funding; Acerta: Consultancy, Research Funding; Dava Oncology: Honoraria; BeiGene: Research Funding; Kite Pharma: Research Funding; Juno Therapeutics: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asana biosciences, Beigene, Celgene, Juno, Kite, Onyx, Pharmacyclics: Research Funding. Fayad:Seattle Genetics: Consultancy, Research Funding. Westin:Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; ProNAi: Membership on an entity's Board of Directors or advisory committees.

Early Assessment of Treatment Response in Acute Myeloid Leukemia Using FLT PET/CT Imaging: A Trial of the ECOG-ACRIN Cancer Research Group (EAI141)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-31
Author(s):  
Robert Jeraj ◽  
Fenghai Duan ◽  
Ryan J. Mattison ◽  
Lale Kostakoglu ◽  
Daniel A. Arber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Post Treatment ◽  
Leukemia Cells ◽  
Flt Pet ◽  
Pet Ct ◽  
Pre Treatment ◽  
Acute Myeloid

Introduction: Patients with acute myeloid leukemia (AML) are often treated with intensive induction chemotherapy to achieve complete remission (CR). Early response to standard anthracycline plus cytarabine induction (7+3) is assessed by a day 14 nadir bone marrow biopsy. The nadir marrow has limitations, though, including sampling issues and ambiguity as to whether blasts are leukemia cells vs. regenerating marrow. In prior studies, the predictive value for remission of the nadir marrow is only 67-84%. A more accurate predictor of residual disease (RD) would give clinicians an opportunity to modify therapy earlier. Positron emission tomography (PET/CT) with 3'-deoxy-3'-[18F]fluorothymidine (FLT) is a molecular imaging modality that can assess cellular proliferation in the bone marrow compartment. A prior single-institution pilot study showed a significant difference in the marrow FLT uptake between patients with AML who achieved CR and those who had RD after count recovery. Methods: EAI141 was an ECOG-ACRIN-led, prospective, multi-center study designed to assess FLT PET/CT as a predictor of CR after AML induction. The primary objective was to evaluate the predictive value of post-treatment FLT PET/CT imaging for detecting RD, with the secondary objectives of evaluating the predictive value for detecting CR and estimating the sensitivity and specificity. Maximum standardized uptake value (SUVmax) of &gt; 7 g/mL in total bone marrow compartment was chosen prospectively based on data from a pilot study as a marker for presence of leukemia cells at nadir. The predictive values, sensitivity, and specificity of the FLT PET/CT and the nadir bone marrow biopsy were calculated. Eligible subjects were 18 years or older with previously untreated AML who were to receive induction with 7+3. Subjects underwent a nadir marrow biopsy and an FLT PET/CT scan 10-17 days after starting induction, and prior to any re-induction if disease was noted on the nadir marrow. A recovery marrow was performed 28-35 days after initial treatment or re-induction to assess CR or RD. Subjects could undergo an optional pre-treatment scan. Relapse-free survival (RFS) and overall survival (OS) were additional clinical outcomes. Results: 87 subjects from 9 centers were enrolled between 2016-2018, and 61 were considered evaluable. Reasons for being not evaluable included study ineligibility (n=3), no post-treatment scan (n=13), and no remission marrow (n=10). Median age was 58 years (range 21-73); 56% were men and 44% were women. CR was achieved in 56% (34/61). Treatment was a single induction course in 79% (48/61) and re-induction in 21% (13/61). Predictive value based on FLT PET/CT was 60% (9/15, 95% CI 32%-84%) for RD and 61% (28/46, 95% CI 45%-75%) for CR. Of patients who achieved CR, 28/34 had SUVmax ≤ 7 g/mL (sensitivity of 82%) and 9/27 of those who did not had high SUVmax &gt; 7 g/mL (specificity 33%). Predictive value of an aplastic marrow was 59% (26/44) for CR and 56% (9/16) for RD. Of patients who achieved CR, 26/33 had marrow hypoplasia (sensitivity 79%) and 9/27 with RD had disease in the nadir marrow (specificity 33%). Significant heterogeneity of bone marrow compartment post treatment (SUVhetero ranging from 0.24 to 1.07) was observed in FLT-PET/CT scans. Heterogeneity of bone marrow compartment decreased about 50% from pre-treatment to post-treatment FLT PET/CT. OS for all participants, stratified by post-treatment FLT PET/CT response and nadir marrow results, are summarized in the Figure. Conclusions: Although this study did not show significant advantage of FLT PET/CT compared to nadir marrow to predict RD or CR on the average, it did show signal heterogeneity in the study population that may be relevant to disease biology not appreciated by a single sampling site for the nadir or remission marrow. For example, in patients with false negative nadir biopsy, in approximately 20% of patients assessment with FLT PET/CT was correct, likely reflecting bone marrow heterogeneity and limitation of a single point sampling. Similarly, in almost 60% of patients with false positive nadir biopsy, FLT PET/CT assessment was correct. Figure 1 Disclosures Jeraj: AIQ Solutions: Current equity holder in private company. Kostakoglu:F. Hoffmann-La Roche: Consultancy. Strickland:KiTE: Consultancy; Kura: Consultancy; Astellas: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Sunesis: Research Funding; ArcherDx: Consultancy; AbbVie: Consultancy. Uy:Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Astellas Pharma: Honoraria. Perlman:GE Healthcare: Research Funding; AIQ: Research Funding.

Examining the Outcomes of Watchful Waiting (WW) Among US Patients with Advanced Stage Follicular Lymphoma (FL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 775-775 ◽  
Author(s):  
Rajni Sinha ◽  
Michelle Byrtek ◽  
Nutan J. DeJoubner ◽  
Ajay K. Nooka ◽  
Michael Taylor ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Research Funding ◽  
Cox Regression ◽  
Single Agent ◽  
Advanced Stage ◽  
Free Survival ◽  
Multivariable Logistic Regression ◽  
Starting Point ◽  
Significant Difference

Abstract Abstract 775 Introduction: WW has been an initial strategy for advanced stage FL because randomized trials showed no clear benefit for immediate initiation of therapy with single agent alkylators when compared to deferring therapy (Brice, JCO 1997; Ardeshna, Lancet 2003), although a recent trial raises questions about WW in the era of rituximab (R) based frontline therapies (Ardeshna, ASH Meeting 2010). Methods: The NLCS is a prospective, multicenter, observational study collecting data on 2,738 newly diagnosed pts with FL diagnosed from 2004–2007 at 265 US sites (80% non-academic). Initial management decisions were made by the treating physician and were categorized as WW (for pts who did not receive therapy in the 90 period following diagnoses and were coded by physicians as WW) or active therapy (AT) including: R alone, R-chemotherapy (RChemo), or other. Baseline clinical factors and treatment setting were compared for WW and AT pts using multivariable logistic regression. Kaplan-Meier (KM) estimation and Cox models were used to evaluate progression-free survival (PFS), time to 2nd and 3rd line management strategy (TT2, TT3), transformation-free survival (TFS), PFS following 1st AT, and overall survival (OS). Due to differences between WW and AT groups, adjusted Cox regression models are presented for the primary analysis of study endpoints controlling for sex, community vs. academic practice site, FL grade, and FLIPI. All time to event analyses were calculated from the 90 day period following diagnosis to allow enrollment in WW, and PFS was calculated from the starting point to the clinician's recording of progressive disease (PD) or death. Results: Among 1,737 pts presenting with stage III/IV FL in the analysis population, 237 underwent WW and 1,500 received AT immediately following diagnosis including: 241 pts treated with R, 1046 with RChemo, 26 with radiation, and 187 other therapies. Multivariable logistic regression demonstrated that the following pt characteristics were predictive of selection of WW rather than initial AT: age > 60 years, no B-symptoms, FL grade 1 or 2, ECOG PS = 0, ≤1 extranodal sites involved, and LDH ≤ULN (all p < 0.05). Median PFS and TT2 were 27 and 35 months for WW, and 64 months and not reached for AT. With a median follow-up of 55 months, 17% of WW pts and 19% of AT pts have died, with no significant difference in OS between WW and AT (p = 0.31). Compared with WW, RChemo improved PFS: adjusted Hazard Ratio (HR) = 0.36, TFS: HR=0.65, TT2: HR=0.48, and TT3: HR=0.53, all p<0.01. For most of the 145 WW pts that later initiated an AT, PD was recorded as the reason for treatment (83%). ATs following WW were: R (51, 35%), RCVP (21, 14%), RCHOP (16, 11%), R + other chemo (23, 16%), investigational (15, 10%), chemo alone (9, 6%), radiation (8, 6%), BMT (1, 1%), or other therapy (1, 1%). The median PFS for R was 42 months when given at diagnosis and 55 months when given following WW. The median PFS for RChemo was 71 months when given at diagnosis and 37 months when given following WW. After adjustment for FLIPI, FL grade, sex, practice setting, and type of treatment, WW adversely affected PFS following 1st AT, H=2.02, p <0.0001. Conclusions: FL pts in the US who undergo initial WW are treated at a median of nearly 3 years. Median PFS following RChemo, but not R is shorter when utilized after period of WW than at diagnosis – albeit in different clinical circumstances. Additional follow-up is needed to assess the tradeoff of this time without therapy with as yet no observable differences in OS. Disclosures: Sinha: CELGENE: Research Funding. Friedberg:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees. Link:Genentech: Consultancy. Flowers:Spectrum: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech/Roche (unpaid): Consultancy; Novartis: Research Funding; Seattle Genetics: Consultancy.

Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 955-955 ◽  
Author(s):  
Anas Younes ◽  
Joseph M. Connors ◽  
Steven I. Park ◽  
Naomi N.H. Hunder ◽  
Stephen M. Ansell
Keyword(s):  
Hodgkin Lymphoma ◽  
Combination Treatment ◽  
Research Funding ◽  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Frontline Therapy

Abstract Abstract 955 Background: Hodgkin lymphoma (HL) is a lymphoid neoplasm defined by the presence of CD30-positive Hodgkin Reed-Sternberg (HRS) cells in a background of inflammatory cells. Frontline treatment is generally ABVD alone or in combination with other chemotherapy regimens or radiation. Although a standard ABVD regimen is curative for the majority of patients with advanced stage HL, up to 30% of patients will require a second-line therapy. Brentuximab vedotin (SGN-35) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). In a phase 2 study, an objective response rate of 75% and multiple durable complete remissions (CRs) (34%) were obtained with single-agent brentuximab vedotin in highly treatment-refractory patients with HL. Methods: A phase 1, open-label, multicenter study is being conducted to evaluate the safety of brentuximab vedotin when administered in combination with standard therapy (ABVD) or a modified standard (AVD) (ClinicalTrials.gov #NCT01060904). Patients received doses of 0.6, 0.9, or 1.2 mg/kg brentuximab vedotin with standard doses of ABVD or 1.2 mg/kg brentuximab vedotin with AVD, depending upon cohort assignment. The combination regimens were administered on Days 1 and 15 of each 28-day cycle for up to 6 cycles of therapy. Each regimen evaluated a dose limiting toxicity (DLT) period, defined as any Cycle 1 toxicity requiring a delay of ≥7 days in standard ABVD or AVD therapy. Determination of antitumor activity is based on investigator assessment of objective response according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Results: Interim data are presented for the first 31 patients treated. Six patients received 0.6 mg/kg, 13 received 0.9 mg/kg, and 6 received 1.2 mg/kg with ABVD; 6 patients received 1.2 mg/kg with AVD. Baseline characteristics included: Stage IV, 55%; IPI score ≥4, 29%; male, 77%; median age, 35 years (range, 19–59). Combination treatment was generally well tolerated, with no DLT observed up to 1.2 mg/kg in either regimen. Overall, AEs reported in ≥45% of patients, regardless of severity, were nausea and neutropenia (77% each); peripheral sensory neuropathy (48%); and fatigue (45%). Infusion-related reactions occurred in 23% of patients. Grade 3/4 AEs observed in >10% of patients were neutropenia (74%), febrile neutropenia (16%), and anemia (13%). No Grade 5 events were observed. Overall, 6 patients discontinued combination treatment due to an AE. In the ABVD cohorts (n=25), AEs of pulmonary toxicity, dyspnea, and interstitial lung disease that could not be distinguished from bleomycin toxicity led to discontinuation of bleomycin in 7 patients. Five of these 7 patients continued treatment with AVD and brentuximab vedotin. All 10 patients who had a response assessment available after completion of frontline therapy achieved CR. Currently, an expansion cohort of approximately 20 patients is enrolling to explore 1.2 mg/kg brentuximab vedotin combined with AVD therapy. Conclusions: In this interim analysis of 31 patients with newly diagnosed HL, the maximum tolerated dose in combination with ABVD or AVD was not reached; no DLT was observed up to 1.2 mg/kg, the maximum planned dose. Brentuximab vedotin treatment was associated with manageable AEs; the most frequent AEs in the study were nausea and neutropenia. The safety profile observed thus far in this study suggests that brentuximab vedotin has potential for combination therapy with ABVD or AVD. Updated safety and response data will be presented at the meeting. Disclosures: Younes: Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau, Travel Expenses; Novartis: Honoraria, Research Funding, Speakers Bureau; Sanofi-Aventis: Honoraria, Research Funding, Speakers Bureau; Genentech: Research Funding; SBIO: Research Funding; Syndax: Research Funding; Celgene: Speakers Bureau; Gilead: Honoraria; Pharmacyclic: Honoraria. Off Label Use: Brentuximab vedotin (SGN-35) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). It is an investigational agent that is being studied in CD30+ malignancies. Connors:Seattle Genetics, Inc.: Research Funding. Park:Seattle Genetics, Inc.: Research Funding. Hunder:Seattle Genetics, Inc.: Employment, Equity Ownership. Ansell:Seattle Genetics, Inc.: Research Funding.

scholarly journals Pre-treatment maximum standardized uptake value predicts outcome after frontline therapy in patients with advanced stage follicular lymphoma

Haematologica ◽  
2019 ◽  
Vol 105 (7) ◽  
pp. 1907-1913 ◽  
Author(s):  
Paolo Strati ◽  
Mohamed Amin Ahmed ◽  
Nathan H. Fowler ◽  
Loretta J. Nastoupil ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Standardized Uptake Value ◽  
Advanced Stage ◽  
Maximum Standardized Uptake Value ◽  
Frontline Therapy ◽  
Pre Treatment

scholarly journals Terraflow, a New High Parameter Data Analysis Tool, Reveals Systemic T-Cell Exhaustion and Dysfunctional Cytokine Production in Classical Hodgkin Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3516-3516
Author(s):  
Dan Freeman ◽  
Linda Lam ◽  
Tri Li ◽  
Jason Alexandre ◽  
Bruce G. Raphael ◽  
...  
Keyword(s):  
T Cells ◽  
Data Analysis ◽  
T Cell ◽  
Research Funding ◽  
Cell Types ◽  
Post Treatment ◽  
Cancer Center ◽  
T Helper ◽  
Pre Treatment ◽  
Analysis Platform

Abstract Background Classical Hodgkin lymphoma (cHL) is characterized by rare, malignant Hodgkin/Reed Sternberg (HRS) cells that shape their microenvironment (TME) to inhibit anti-tumor immune response. Systemic immune dysregulation may influence treatment response and toxicity, but the systemic influence of the TME is less well described. The wide variety of proteins measured in high-parmater flow cytometry make it a powerful tool for immune monitoring, but presents challenges in immuno-monitoring. Combinatorial expression of these proteins defines cell types that may influence disease. TerraFlow is a fully automated data analysis platform that evaluates millions of phenotypes and selects the populations that best predict clinical variables. The analysis can be performed using classical Boolean gates or a non-gating approach that approximates gates without using manual thresholds, allowing immunophenotypes to be comprehensively surveyed for disease associations. The platform was used to find phenotypes that discriminate healthy versus cHL patients (AUC = 1) and pre versus post treatment patient phenotypes(AUC = 0.79). Methods Human Subjects: Informed consent was obtained from cHL patients (N=44) treated at the Perlmutter Cancer Center (PCC) at NYU Langone Health and New York Presbyterian Weil Cornell (NYP) between 2011 and 2016. Blood samples were drawn at multiple time-points, for this study pre-treatment and 3 month post-treatment samples were used. Age-matched, cryopreserved healthy donor PBMC (n=25) were obtained from STEMCELL Technologies (Cambridge, MA).Patient-derived blood was processed for isolation of PBMC, stained analyzed on a Symphony Flow Cytometer (BD Biosciences, San Jose, CA). Analysis: Data was analyzed using an original platform called terraFlow. Many immune cell subsets are defined by the combinations of proteins they express. TerraFlow systematically evaluates millions of cell types by generating every possible combination of 1 to 5 markers. A network-based algorithm then selects the "best" phenotype from each set of inter-related combinations based on statistical power and ease of interpretation. Each phenotype is defined using a minimal gating strategy that can be replicated in a diagnostic panel or cell sorter. Together, phenotypes describe all the major differences between patient groups. A new platform developed by Epistemic AI was used to mine scientific literature and interpret selected phenotypes. Results We observed clear perturbations in the cHL systemic T-cell compartment pre-treatment as shown in Figure 1. These include higher levels of activated (CD278+), exhausted (CD366+, PD1+, CD152+), and suppressive (GITR+) T-cells compared to healthy donors, and diminished levels of T-cells producing effector cytokines (like IFNγ and IL4). Subsets of cytokine-producing cells that co-express markers of exhaustion (i.e., TNF+ CD366+ cells) are also elevated in cHL patients. Finally, T-cells expressing CD127 a receptor for IL7 involved in homeostatic renewal of cells and observed on naive and central memory T-cells are reduced. Taken together, these findings suggest that in cHL the systemic T-cell compartment is shifted toward a more exhausted profile, and away from less differentiated cells, with the potential for self-renewal. Our data also demonstrates a shift from T-helper 1 and T-helper 2 type toward T-helper 17 cells suggesting that T-cell effector function may be reduced. Conclusion Using a novel data analysis platform, TerraFlow we demonstrate dysregulation in systemic T cell function in cHL patients pre-treatment that persists within 3 months of completing therapy. Associations of phenotypes with clinical variables, and post-treatment phenotypes will be described in detail at the meeting. Our results detail new immunotherapy and biomarker research targets, and suggest novel strategies for combination therapies. Figure 1 Figure 1. Disclosures Li: BD Bioscience: Current Employment. Ruan: Kite Pharma: Consultancy; AstraZeneca: Research Funding; BMS: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Pharmacyclics: Research Funding; Seagen: Consultancy. Diefenbach: Incyte: Research Funding; Trillium: Research Funding; Celgene: Research Funding; IGM Biosciences: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Gilead: Current equity holder in publicly-traded company; AbbVie: Research Funding; Perlmutter Cancer Center at NYU Langone Health: Current Employment; MEI: Consultancy, Research Funding; Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; IMab: Research Funding; Morphosys: Consultancy, Honoraria, Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding.

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