tbuckley/cabot-search huggingface dataset:
Survival outcomes in primary orbital diffuse large B-cell lymphoma.
Authors: Firas Baidoun, Bradford S. Hoppe, Han W. Tun, Muhamad Alhaj Moustafa
Journal: Journal of Clinical Oncology (2024)

e19075 Background: Orbital diffuse large B-cell lymphoma is a rare entity accounts for less than 1% of all non-Hodgkin lymphoma cases. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with primary orbital DLBCL between 2004 and 2020. All patients aged ≥ 18 years diagnosed with primary orbital DLBLC were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 404 patients with primary orbital DLBCL. Out of whom 233 (58%) were females, 326 (81%) were White non-Hispanic, 29 (7%) were White Hispanic and 16 (4%) were African Americans. 113 (28%) received chemotherapy only, 76 (19%) received radiation only, 113 (28%) received chemoradiation, 79 (20%) did not receive any treatment and 23 (6%) had unknown treatment status. The median age at diagnosis was 71 years (range 28-90). The median follow-up time was 132 months (95%CI 117-147), the median overall survival (mOS) for the whole cohort was 110 months (95%CI 82-138). Among patients with known treatment status and vital status of last contact (N=381), patient who received chemoradiation had significantly better mOS compared to patients who received radiation only (169 vs 67 months, P=0.002), but there was no statistically significant difference in mOS between chemoradiation and chemotherapy only (169 vs 124 months, P=0.068) or between chemotherapy only and radiation only (124 vs 67 months, P=0.213). On multivariate analysis, older age and Charlson-Deyo score of 2 were associated with worse OS (HR 1.072 95%CI 1.055-1.089; P&lt;0.001, HR 2.292 95%CI 1.099-4.778; P=0.027, respectively). Compared to no treatment, only chemoradiation was associated with better OS (HR 0.509 95%CI 0.332-0.778; P=0.002), whereas chemotherapy only and radiation only did not add a survival benefit (HR 0.909 95%CI 0.598-1.381; P=656 and HR 0.766 95%CI 0.496-1.185; P=0.231). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in primary orbital DLBCL compared to single treatment modality.
Concordance between physician response assessment and a novel method per Lugano criteria in patients with lymphoma using real-world data.
Authors: Richard Scott Swain, Andrew J. Klink, Kristin M. Zimmerman Savill, Parisa Asgarisabet, Bindu Kalesan, Alexandrina Balanean, Harlen Hays, Jill Kaufman, Lindsay McAllister, Hsing-Ting Yu, Jalyna R. Laney, Nicholas C. Richardson, Catherine C. Lerro, Fatima Rizvi, Jonathon Vallejo, Kun Wang, Marc R. Theoret, Donna Rivera, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2024)

e19082 Background: Clinical response assessment criteria, such as RECIST v1.1 and Lugano 2014, provide a standardized approach to assess treatment effectiveness in oncology clinical trials. Corresponding methodologies are needed for real-world data (RWD) to improve interpretability alongside clinical trial data and facilitate replication of results across RWD studies. We developed a RWD novel methodology, real-world Lugano (rwLugano), derived from Lugano 2014 criteria to classify lymphoma treatment response among patients with diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective multisite RWD study identified adult patients with DLBCL treated with first line chemoimmunotherapy in US clinical practice (01JAN2015-31DEC2022). Participating sites abstracted clinical data via medical chart review and positron emission tomography-computed tomography (PET-CT) reports. Deidentified digital PET-CTs taken at treatment initiation and first response assessment were uploaded for BICR. Three distinct methods were used to assess treatment response: 1) physician-reported obtained from unstructured clinical notes in medical records, 2) rwLugano calculated using data (i.e., components of Lugano 2014) from PET-CT reports, and 3) BICR adjudication by two lymphoma radiologists using Lugano 2014 criteria. We compared the proportion of patients by response category: complete (CR), partial (PR), stable (SD) and progressive (PD) for each method. Analyses included agreement (%), concordance (Cohen’s kappa [κ]), and odds ratios with 95% confidence interval (OR; 95%CI) estimated using multivariable generalized linear mixed models (GLMM) adjusted for baseline characteristics. Results: The study identified 174 patients with DLBCL (female n=71 [41%]; white n=135 [78%]; Hispanic n=13 [7%]; mean age 66 years). Fewer patients were classified as CR at initial response via physician-reported response (n=111, 64%) compared to rwLugano (n=145, 83%), and BICR (n=142, 82%). Overall and CR agreement with BICR (see Table) was higher for rwLugano (overall: 83%, κ=0.49; CR: 86%, κ=0.50) than physician-charted response (overall: 72%, κ=0.45; CR: 76%, κ=0.43). In GLMM models, physician-charted response underestimated CR compared to BICR (OR=0.22, 95%CI:0.12-0.43), whereas rwLugano was statistically similar to BICR (OR=1.2, 95%CI:0.6-2.4). Conclusions: This study found that physician-reported response may underestimate CR at initial response, and rwLugano may be more consistent with BICR for treatment response assessment. Use of rwLugano warrants further evaluation as a methodology to assess treatment response in RWD lymphoma research. [Table: see text]
Second line immune targeted therapies in relapsed or refractory diffuse large B-cell lymphoma: A network meta-analysis.
Authors: Aneesha Fathima Syed Mohamed, Renuka Kandikatla, Vinod Kumar Yakkala, Loriel Solodokin, Joanne Doucette, Ismaeel Yunusa, Tewodros Eguale
Journal: Journal of Clinical Oncology (2024)

e19071 Background: Relapsed or refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) patients undergo multiple lines of burdensome therapies. We conducted a network meta-analysis (NMA) of phase 3 randomized control trials (RCTs) to evaluate the effectiveness of second-line (2L) immune targeted treatments (ITTs), including chimeric antigen receptor (CAR)-T cell therapies in R/R DLBCL patients, focusing on overall survival (OS), event-free survival (EFS), progression-free survival (PFS), overall response rate (ORR) and complete response (CR). Methods: In a systematic review, we searched RCTs from PubMed, Embase and Cochrane Library spanning January 2016 to September 2023.We included studies reporting on adults (≥18 years) DLBCL patients experiencing R/R to first-line anti-CD20 antibody and anthracycline-containing regimen. RCTs comparing ITTs with SOC (2L salvage chemoimmunotherapy regimens followed by stem cell transplantation) were included. Frequentist fixed-effect model was utilized to estimate hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for binary outcomes (ORR and CR) with corresponding 95% confidence intervals (CIs). We ranked treatment effectiveness based on the surface under the cumulative ranking curves (SUCRA). Results: Our search identified 539 records; four RCTs contributed to the NMA: three comparing CAR-Ts, axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel) with SOC, and one comparing ofatumumab + cisplatin, cytarabine, dexamethasone (O-DHAP) with SOC. Axi-cel significantly improved OS compared to both tisa-cel (HR, 0.59; 95% CI, 0.36-0.96) and SOC (HR, 0.73; 95% CI, 0.55-0.98). For EFS, axi-cel (HR, 0.38; 95% CI, 0.27-0.53) and liso-cel (HR, 0.32; 95% CI, 0.21-0.51) showed significant improvement compared to ODHAP. Axi-cel and liso-cel improved EFS significantly when individually compared to tisa-cel, and SOC.Axi-cel (HR, 0.51; 95% CI, 0.39-0.67) and liso-cel (HR, 0.4; 95% CI, 0.26-0.61) improved PFS significantly when compared to SOC. Axi-cel and liso-cel also significantly improved PFS when individually compared to ODHAP. In terms of ORR, Axi-cel (OR, 5.93; 95% CI, 3.63- 9.68) and Liso-cel (OR, 6.96; 95% CI, 3.37- 14.37) produced significantly higher ORR compared to SOC. Axi-cel and liso-cel had higher CR significantly when individually compared to ODHAP, tisa-cel, and SOC.In the SUCRA rankings, axi-cel was the most effective for OS, liso-cel ranked the most effective for EFS and PFS. Conclusions: Axi-cel was consistently associated with improved OS and EFS when compared to tisa-cel and SOC while liso-cel improved EFS and PFS over ODHAP and SOC. ORR and CR were higher for axi-cel and liso-cel over tisa-cel, ODHAP and SOC. Results are constrained by lack of multiple studies for each treatment comparison.
Exploring the role of the combination of FDG PET plus whole body MRI for staging newly diagnosed and relapsed/refractory multiple myeloma: A prospective trial.
Authors: Claudio Cerchione, Davide Nappi, Matteo Marchesini, Delia Cangini, Sonia Ronconi, Michela Ceccolini, Andrea Prochowski Iamurri, Federica Matteucci, Giorgia Simonetti, Gerardo Musuraca, Giovanni Martinelli, Alice Rossi
Journal: Journal of Clinical Oncology (2024)

7512 Background: The integration of FDG-PET/TC and WB-MRI in the diagnosis of MM may results in higher accuracy to detect bone lesion compared to them alone. This could be translated into better outcomes if early detection of myeloma defining events leads to earlier induction or re-induction treatments. Methods: In our Institution, from January 2021 to January 2023, we performed a prospective trial enrolling 73 consecutive newly diagnosed and relapsed/refractory MM (median age 63 years - range 85-35), according to IMWG, in which WB-MRI was performed according to MY-RADS criteria in combination with FDG PET/CT. 31/73 (42%) had a newly diagnosed MM, 25/73 (34%) were in follow-up after autologous stem cell transplantation and 17/73 (23%) patients were affected by relapsed/refractory MM. Subsequently, in 2 cases WB-MRI were aborted and not diagnostic so patients were excluded from the final analysis. Results: In these 71 patients: 52/71 (73%) cases of concordance of WB-MRI and 18F PET-CT, 18/71 (25%) cases of discordance. In this group 15/18 (83%) cases FDG-PET/CT was negative and WB-MRI showed positive findings according to MYRADS criteria (5 micronodular pattern, 9 diffuse pattern e 1 focal pattern) (Figure 1 Newly diagnosed MM – diffuse pattern in WB-MRI, PET negativity), in 3/18 (17%) FDG-PET/CT was positive for focal lesions and WB-MRI was negative. IMWG criteria showed concordance with WB-MRI data in 16/18 (89 %), in 2/18 (11%) case of follow-up after autologous stem cell transplantation PET-CT showed a relapsed focal lesion while WB-MRI was negative. Accuracy of WB-MRI was 69/71 (97%), whilst PET-CT was 55/71 (77%). These results are in agreement with the literature data about the ability of WB-MRI to depict diffuse and micronodular pattern of bone marrow infiltration. Conclusions: Our preliminary results support a potential complementary role of WB-MRI and FDG PET/CT findings, on the management of patients with MM at both diagnosis and relapse. To date, there is no wide availability of WB-MRI because in concerning about costs and technical issues, but data are consistent with its possible future leading role in MM diagnostic work-up.
Characteristics and outcomes of plasmablastic lymphoma in a predominantly Hispanic population.
Authors: Adam Alexander Kolawa, Julian Hardy McLain, Shirley Ye, Imran Siddiqi, Ann Mohrbacher
Journal: Journal of Clinical Oncology (2024)

e19079 Background: Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B-cell lymphoma and is frequently associated with immunosuppression. PBL displays immunoblastic morphology and a plasma cell immunophenotype. Data regarding patient characteristics, outcomes, and optimal treatment for this disease is limited. The reported prognosis of patients with PBL has been historically poor, with median overall survival ranging from 6 to 18 months. A recent publication of the SEER/NCDB database found a significantly improved OS in the Hispanic population (HR 0.7, p=0.014). This study investigates demographic, treatment, and survival outcomes for a primarily Hispanic PBL population. Methods: We identified 42 cases of pathologically confirmed PBL at two high volume tertiary care centers in Southern California between March 2010 and June 2023. Chart review was used to collect data on clinical presentation, treatment, and outcomes. Results: Median age of patients at diagnosis was 46 years (range 17-91 years) and 90% were male. Hispanic patients represented 81% of the total cohort. Predisposing immunosuppression was identified in 60%, and 50% of the total cohort were HIV-positive. Pathologic analysis showed EBV positivity by EBER in situ hybridization in 67%. 76% of patients presented with advanced disease (Stage III/IV). The most common regimens were EPOCH (27%) and V-EPOCH (49%). Response rates and CR rates were 63% and 50% respectively. Median follow-up was 10.5 months. OS was 72% at 1-year and 60% at 2-years. Conclusions: Our cohort demonstrated a 1-year OS of 72% compared to the 56% 1-year OS for PBLs in the SEER/NCDB database. There was no statistically significant difference in survival between the Hispanic and Non-Hispanic cohorts in our study. However, this is likely due to the small sample size in the latter. Notably, our patient population had more advanced disease at presentation (76% Stage III/IV) than the SEER/NCDB cohort (60% Stage III/IV). This improved survival is likely multifactorial, but could represent ethnic differences in PBL biology, high EBV positivity, and the frequent utilization of higher intensity regimens (EPOCH/V-EPOCH = 76%). Further studies are needed to better characterize this disease in the Hispanic population. [Table: see text]
Epidemiological insights and survival patterns of HHV8-positive diffuse large B-cell lymphoma (HDN) associated with multicentric Castleman disease (CD): A comprehensive analysis using SEER database.
Authors: Vanthana Bharathi, Aamer Farooq
Journal: Journal of Clinical Oncology (2024)

e19080 Background: Castleman Disease (CD) encompasses a diverse range of lymphoproliferative disorders, featuring subtypes like unicentric CD (UCD), multicentric CD (MCD), HHV-8 associated multicentric CD, and HHV-8 negative/idiopathic MCD (iMCD). HDN is a rare and aggressive lymphoma often linked with HHV8-positive multicentric Castleman disease (CD). It often manifests without any other obvious symptoms and may be confused with other causes of lymph nodal enlargement. The epidemiology, treatment patterns, and survival outcomes of HDN are poorly understood, prompting this study to explore CD's epidemiology using the National Cancer Institute's SEER database. Methods: Using SEER 2000-2020, we identified 77 CD cases through ICD Code 9738 for Large B Cell Lymph HHV8 Multicentric Castleman Disease. Demographic, socio-economic, clinicopathologic characteristics, and survival outcomes were assessed. Secondary-primary malignancy risk (SIR) and mortality risk (SMR) were both calculated with observed to expected (O:E) ratios from the general population, with significance set at P &lt; 0.05 and 95% CIs. Results: The median age at diagnosis was 51.7 years. The primary site distribution was mainly nodal (77.9%), while the extra nodal sites were rarely involved (22.1%). Only 3.8% of patients received radiotherapy, while 50.6% received chemotherapy. The patients were predominantly male (80.5%) and White (63.6%). Patients with a household income above $65,000 accounted for 75.3%. At diagnosis, 33.7% of the patients were married. Survivors had increased risk of malignancies at all sites (O:E 7.75, 95% CI: 0.94-28.01) and significantly increased risk of all solid tumors (O:E 8.95, 95% CI: 1.08-32.32), malignancy of kidney and renal pelvis (O:E 88.37, 95% CI: 2.24-492.36) and Kaposi Sarcoma (O:E 2,329.89, 95% CI: 58.99-12,981.34) within one year. The two most common causes of death in the CD cohort were infectious and parasitic diseases, including HIV, and malignant cancers. The 1-year, 3-year and 5-year Overall survival was 63.6%, 59.7%, and 54.4% respectively, and the corresponding Cancer-specific survival was 68.8%, 68.8%, and 65.7%, respectively. Conclusions: This study sheds light on the epidemiology of HDN. Despite the rarity of HDN, our analysis of data reveals key demographic and clinical characteristics of HDN patients. The survival outcomes indicate a challenging landscape, with notable risks of secondary malignancies, particularly within the first-year post-diagnosis. The identification of specific risks, treatment patterns, and survival rates contributes valuable insights for future research and clinical management strategies in addressing this aggressive lymphoma.
Effect of dose-adjusted melphalan on MRD-negativity to full dose melphalan in patients with multiple myeloma post-autologous stem cell transplant.
Authors: Jeries Kort, James John Ignatz-Hoover, Nikolas Naleid, Frank Oley, Brenda W. Cooper
Journal: Journal of Clinical Oncology (2024)

7557 Background: Despite significant therapeutic advancements, Multiple Myeloma (MM) remains an incurable disease. Autologous stem cell transplantation (ASCT) is a standard treatment for eligible patients, with high-dose melphalan (MEL200) as the preferred conditioning regimen. Reduced-dose melphalan (MEL140) is used for older or less fit patients. However, this was not prospectively studied and there has been ongoing debate about the efficacy of reduced dosing. This study aimed to investigate the impact of melphalan dose on minimal residual disease (MRD) negativity rates in MM patients undergoing upfront ASCT. Methods: We conducted a retrospective, single-center study involving 74 MM patients who underwent ASCT between 2018 and 2022 at UHCMC, Cleveland, OH and had MRD testing done after transplant. MRD testing was performed using the ClonoSEQ next generation sequencing platform. Results: Median age was higher in the MEL140 group compared to MEL200 (70.3 vs 59.8 years), both groups were similar in terms of sex and race distribution, BMI and KPS scores. Both groups have comparable ISS staging and high-risk cytogenetics. Similar numbers of lines of treatment prior to transplant were seen, with approximately 64% having only one line. First-line induction therapy included triplet therapy (Lenalidomide, Bortezomib, and Dexamethasone) in 73% of patients. Depth of remission at transplant was comparable between groups. MRD negativity rates at 10 -5 and 10 -6 were comparable between MEL140 and MEL200 groups (64% and 39% in MEL140; 61% and 41% in MEL200; p=0.8 and 0.7 respectively). Sustained MRD negativity at 10 -5 over at least 12 months was also comparable (43% in MEL140; 50% in MEL200, p=0.8). After a median follow-up of 37 months, PFS was not reached for either group (p=0.69). Patients achieving MRD negativity at levels of 10 -5 had a not reached median PFS, while those not achieving MRD negativity had a median PFS of 41 months (95%CI 23-NR; p=0.024). There was no significant difference in hospital stay duration, time to neutrophil engraftment, readmission rate, or infections within 100 days post-transplant between the MEL140 and MEL200 groups. Conclusions: Our real-world analysis demonstrates that MEL140 yields similar deep post-transplant remissions as MEL200, translating to improved PFS for patients achieving MRD negativity, regardless of the dose used. This is the first report to our knowledge of MRD negativity rate in patients receiving MEL140. [Table: see text]
Uncontrolled diabetes mellitus and the progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans.
Authors: Lawrence Liu, Byron Sigel, Mei Wang, Nikhil Grandhi, Martin W. Schoen, Kristen Marie Sanfilippo, Murali Janakiram, Theodore Seth Thomas, Su-Hsin Chang
Journal: Journal of Clinical Oncology (2024)

7551 Background: Studies have shown that, independent of obesity, the metabolic effects of diabetes mellitus (DM) promote the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). However, it is unclear whether glycemic control is associated with MGUS progression in DM patients. We aimed to evaluate the association between poor glycemic control, measured by HbA1c &gt;6.5%, and progression. Methods: Patients diagnosed with MGUS from 1999-2021 in the Veterans Health Administration (VHA) were identified using a published natural language processing (NLP)-based algorithm. We focused on patients whose MGUS subtype was IgG, IgA, or light chain. We excluded patients lacking body weight measurements from the time of MGUS diagnosis to the end of follow-up to ensure receiving care in the VHA. We further excluded patients with extended gaps &gt;1 year between HbA1c measurements. Time-varying HbA1c measurements during the follow-up, evaluated at 1-day intervals and categorized into uncontrolled (HbA1c &gt;6.5%) or controlled (≤6.5%) DM was the exposure variable. Progression of MGUS to MM was also confirmed by a published NLP algorithm. The association between the time-varying controlled/uncontrolled DM and progression was estimated by multivariable-adjusted hazard ratio (aHR) with death as a competing event. The covariates included sex, race, MGUS subtype as well as age, body mass index, monoclonal protein level, Charlson Comorbidity Index, DM medication, and DM type (type 1, type 2 with insulin-dependency status, type 2 without insulin-dependency status), all at MGUS diagnosis. Same analysis was conducted in a subgroup of patients with non-insulin dependent DM type 2 (NIDDMT2) without insulin use between MGUS diagnosis and the end of follow-up. Results: After applying inclusion and exclusion criteria, we identified 9,682 patients with both DM and MGUS. The multivariable analysis revealed a positive association between poor glycemic control and MM progression (see Table): (aHR 1.27, 95% CI 1.13-1.42). In NIDDMT2 without insulin use (n=3,498), poor glycemic control was associated with MM progression (aHR 1.81; 95% CI 1.57-2.10). Conclusions: For patients with DM and MGUS, the risk of MGUS progression to MM was 27% higher in uncontrolled DM and 81% higher in patients with NIDDMT2. This finding highlights a modifiable risk factor for MM progression in MGUS patients. Future studies should examine if interventions to enhance glycemic control could potentially reduce MGUS progression.