tbuckley/cabot-search huggingface dataset:
First relapse in patients with multiple myeloma: Outcomes and predictors.
Authors: Sukriti Seth, Prashant Kapoor, Francis Buadi, Moritz Binder, Joselle Cook, Angela Dispenzieri, David Dingli, Amie L. Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Lisa Hwa, Miriam A. Hobbs, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Rahma M. Warsame, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2024)

7558 Background: Survival in patients with multiple myeloma (MM) continues to improve with the newer therapies, but there is no clear evidence of a cure and patients continue to relapse. However, most patients have the most extended period without progression with their first-line therapy, and subsequent therapies often provide a shorter duration of response due to the use of drugs with overlapping mechanisms of action and, more importantly, a shorter first remission, pointing toward more aggressive disease biology. With newer immunotherapies being used at 1 st relapse, this may change. We designed this study to explore the natural history of MM after the 1 st relapse and define the predictors of outcome after the initial relapse. Methods: We identified all patients in the Mayo Clinic database diagnosed between Jan 2004-June 2019 who had had initial disease progression. The study cohort included 2005 patients. We explored the overall survival (OS) from the time of documented disease progression or the start of second-line treatment in patients who had not met IMWG criteria before second-line therapy. Front-line therapy was grouped into those with either an IMiD or PI, both IMiD and PI, daratumumab with IMiD and PI, and none of these agents. The IMiD and PI were always used with dexamethasone with or without an alkylator. Results: The median age was 63 (range 24-95) years and 60% were male. The median estimated follow-up from diagnosis for all patients was 86 mos. (95% CI; 82, 88) and the median time to progression from the start of therapy was 25 mos. (95% CI; 24, 26). The median OS from the first progression was 45 mos. (95% CI; 42, 50), 36 mos. for those diagnosed before 2009, and 52-53 mos. for those diagnosed later. On univariate analysis, age &lt;70 at 1 st relapse, RISS I, novel agents in initial therapy, CR in the first line, diagnosis after 2009, initial remission &gt;18 mos, and initiation of therapy before IMWG progression were all associated with improved OS after 1st relapse (Table). On multivariate analysis, age &lt;70, RISS I, initial remission &gt;18 mos, and initiation of therapy before IMWG progression were all associated with improved OS after 1st relapse. Conclusions: The study provides an estimate of the outcomes and significant predictors of outcomes after 1st relapse in patients with MM. These factors should be taken into consideration when designing clinical trials in this patient population. In particular, these factors identify a high-risk group of patients not always identified by baseline characteristics and should be the focus of future trials. [Table: see text]
Clinical outcomes and resource utilization in patients with multiple myeloma admitted with gastrointestinal bleeding.
Authors: Fayaz Khan, Kenan Rahima
Journal: Journal of Clinical Oncology (2024)

e19522 Background: In multiple myeloma (MM) patients, GIB can be due to factors such as abnormal proteins affecting the GI tract, coagulation issues, or secondary conditions like amyloidosis. There's limited scientific evidence examining outcomes among patients presenting with both GIB and MM. Thus, our objective was to assess clinical outcomes in this specific population. Methods: We accessed the National Inpatient Sample from 2017-2020 to identify adult patients with MM hospitalized due to GIB. The primary endpoint was inpatient mortality, with secondary endpoints including length of stay and total hospital charges. We utilized multivariable logistic regression analysis to estimate clinical outcomes, considering a significance threshold of P &lt; 0.05. Results: We identified 4,067,364 hospitalizations with GIB, among which 22,000 (5.9%) presented with MM. Comparing MM and Non-MM cohorts, the mean age was 71.9 vs 67.8 years, males constituted 58% vs 52.2%, and White ethnicity accounted for 55.6% vs 66.1%. The prevalence of obesity was 10.6% vs 14.5%, diabetes mellitus was 32.1% vs 33.8%, chronic obstructive pulmonary disease was 16.9% vs 20.4%, dyslipidemia was 38.5% vs 40.7%, atrial fibrillation was 27.7% vs 25.6%, hypertension was 22.9% vs 34.7%, heart failure (HF) was 30.7% vs 26.4%, peripheral vascular disease (PVD) was 2.9% vs 4.1%, acute kidney injury was 45.6% vs 29.4%, anemia was 26.3% vs 27.7% and chronic kidney disease (CKD) was 51.9% vs 28.6%. Clinical outcomes revealed stark differences between MM and Non-MM cohorts: in-hospital mortality rates were 10.9% vs 6.3% with an odds ratio (OR) of 1.5 (CI 1.4-1.7); LOS was 9.6 days vs 6.7 days (IRR 1.26, CI 1.21-1.32); and hospital charges were $30,006 vs $20,172 (IRR 1.34, CI 1.26-1.42). All data demonstrated a p-value &lt; 0.001 and were adjusted for various factors including age, sex, race, comorbidity indices, obesity, atrial fibrillation, diabetes mellitus, hypertension, peripheral vascular disease, acute kidney injury, chronic kidney disease, nicotine and alcohol use, stroke, acute respiratory failure, and inflation during 2017-2020. Conclusions: Patients hospitalized for GIB and MM were comparatively older, with a larger male population and fewer Caucasians. They exhibited higher Afib, HF, AKI, and CKD rates with lower occurrences of obesity, DM, COPD, dyslipidemia, HTN, anemia and PVD. This group showed a significantly worse mortality rate with prolonged hospital stays and resource utilization. This entails to have prompt medical attention, appropriate management of bleeding, and addressing the underlying causes are crucial in improving outcomes and reducing mortality rates. Treatment strategies often involve a multidisciplinary approach involving oncologists, hematologists, gastroenterologists, and other specialists to provide comprehensive care tailored to the individual's condition.
Survival outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.
Authors: Firas Baidoun, Bradford S. Hoppe, Han W. Tun, Muhamad Alhaj Moustafa
Journal: Journal of Clinical Oncology (2024)

e19074 Background: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL-LT) is an uncommon type of lymphoma predominantly affects elderly patients and is associated with poor outcome. 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 PCDLBCL-LT between 2004 and 2020. All patients aged ≥18 years diagnosed with PCDLBL-LT 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 967 patients with PCDLBCL-LT. Out of whom 516 (53%) were females, 841 (87%) were White non-Hispanic, 41 (4%) were White Hispanic and 37 (4%) were African Americans. 276 (29%) received chemotherapy, 203 (21%) received radiation only, 293 (30%) received chemoradiation, 147 (15%) did not receive any treatment and 48 (5%) had unknown treatment status. The median age at diagnosis was 78 years (range 23-90). The median follow-up time was 87 months (95% CI 74-99), the median overall survival (mOS) for the whole cohort was 42 months (95%CI 37-47). Among patients with known treatment status and vital status of last contact (N=841), patient who received chemoradiation had significantly better mOS compared to patients who received chemotherapy only, radiation only and no treatment (64 vs 41, 39 and 9 months, respectively P&lt;0.001). Patient who received chemotherapy only and radiation only as first line therapy had significantly better mOS compared to patients who received no treatment (41 and 39 vs 9 months, respectively P&lt;0.001), but there was no statistically significant difference in the mOS between chemotherapy only and radiation only (41 vs 39 months, P=0.359). On multivariate analysis, older age, male gender, and Charlson-Deyo score 2 and ≥3 were associated with worse OS (HR 1.061 95%CI 1.050-1.072; P&lt;0.001, HR 1.241 95%CI 1.093-1.482; P=0.017, HR 1.396 95%CI 1.004-1.941; P=0.047 and HR 2.454 95%CI 1.619-3.719; P&lt;0.001 respectively), all type of treatments including chemotherapy only, chemoradiation, and radiation only were associated with better OS (HR 0.576 95% CI 0.443-0.749; P&lt;0.001, HR 0.379 95%CI 0.290-0.495; P&lt;0.001 and HR 0.443 95%CI 0.339-0.578; P&lt;0.001, respectively). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in this uncommon type of lymphoma compared to single treatment modality.
Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel.
Authors: Saurabh Zanwar, Surbhi Sidana, Leyla Shune, Omar Alexis Castaneda Puglianini, Oren Pasvolsky, Rebecca Gonzalez, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, James A. Davis, Megan Herr, Hamza Hashmi, Peter A. Forsberg, Douglas W. Sborov, Shambavi Richard, Jack Khouri, Yi Lin, Krina K. Patel, Shaji Kumar, Doris K. Hansen
Journal: Journal of Clinical Oncology (2024)

7508 Background: Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy in patients with relapsed/refractory multiple myeloma (RRMM). However, outcomes in patients with extramedullary disease (EMD) remain to be better characterized. Methods: We included patients from 11 US academic centers, who were evaluated for EMD and were infused with ide-cel between May 2021 and April 2023. Patients with soft tissue or visceral lesions non-contiguous from bony lesions were classified as having true EMD, with paraskeletal disease classified as non-EMD. Disease responses were evaluated using the IMWG criteria. Time-to-event analyses were performed from the date of ide-cel infusion. Results: Among 351 patients with RRMM treated with ide-cel, 84 (24%) had EMD prior to infusion. Median follow-up for the entire cohort was 18.2 months (95% CI: 17-19.3). Baseline characteristics at ide-cel infusion for EMD and non-EMD cohorts are depicted in the table. For the EMD and non-EMD cohorts, the Day 30 objective response rates (ORR) were 58% vs. 69% (p=0.1), Day 30 ≥complete response rates were 16% vs 24% (p=0.11), the Day 90 ORR were 52% vs 82% (p&lt;0.001), and best ORR were 58% vs 82%, respectively. The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p&lt;0.0001) for the non-EMD cohort. The median duration of response for EMD among day 30 responders was 6.4 months (95% CI: 5.1-8.4). In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.8 (95% CI: 1.2-2.5), p&lt;0.001] after adjusting for ECOG status, revised ISS stage, penta-drug refractoriness, elevated ferritin, prior BCMA-directed therapy and use of bridging therapy. Pattern of progression in the EMD cohort (n=68/84) included EMD site only (21%), hematologic only (22%), or both (57%), with comparable PFS for type of progression (p=0.19). The median overall survival (OS) was 14.8 months [95% CI: 9-Not reached (NR)] for EMD and 26.9 months [95% CI: 26.3 vs NR, p=0.006)] for the non-EMD group. Rates of Grade ≥2 cytokine release syndrome or neurotoxicity syndrome were comparable between the two cohorts. Conclusions: Patients with EMD demonstrate significantly inferior Day 90 ORR and presence of EMD is an independent risk factor for inferior PFS. [Table: see text]
Incidence of any infections and SARS-CoV-2 infections in patients receiving treatment for follicular lymphoma and diffuse large B-cell lymphoma: Real-world evidence from a large US national claims database.
Authors: Omonefe O. Omofuma, Alexander Breskin, Ping Shao, Julius Asubonteng, Alexi N. Archambault, Christian Hampp, Saleem Shariff, Claire Hearnden, Srikanth R. Ambati, Hesham Mohamed
Journal: Journal of Clinical Oncology (2024)

e19061 Background: Non-Hodgkin’s lymphoma is a heterogeneous group of conditions, including the indolent subtype follicular lymphoma (FL) and the aggressive subtype diffuse large B-cell lymphoma (DLBCL). Infections associated with NHL are a major concern due to effects of the underlying disease and its treatment and have been reported to increase with increasing lines of therapy (LoT). However, the risk of infections overall and SARS-COV-2 infections specifically is not well characterized in patients who have received multiple LoTs. The goal of the study was to estimate the exposure-adjusted incidence rates (EAIR) of infections during the COVID-19 pandemic by type, severity and LoT received in patients treated for FL or DLBCL in the real-world setting. Methods: We identified patients in the Optum Clinformatics claims data from October 1, 2015, to June 30, 2023. Patients were aged ≥18 years, enrolled continuously for 365 days before index (start of LoT), and had ≥2 ICD-10 diagnosis codes for FL or DLBCL in the 365 days before index. The EAIR (per 100 person-years, PY) was estimated for infections by type (any infections and SARS-COV-2 [after 1/1/2020]), severity (hospitalized or fatal hospitalizations), and number of LoTs received. Results: A total of 4,799, 1,025 and 510 FL patients were included in the 1L (1 LoT), 2L, and 3L+ cohorts, respectively. The EAIR of infections resulting in hospitalization in 1L, 2L, and 3L+ cohorts were 20.6 (95% confidence interval (CI): 19.0-22.3), 30.2 (25.5-35.9), and 44.2 (35.4-55.3) per 100-PY for any infection; and 4.6 (4.0-5.4), 4.4 (3.0-6.5) and 8.3 (5.3-13.2) per 100-PY for SARS-COV-2 infections, respectively. The EAIR of fatal hospitalizations were 4.0 (3.4-4.8), 8.6 (6.4-11.5), and 13.9 (9.7-20.0) per 100-PY for any infection; and 1.3 (1.0-1.7), 1.6 (0.8-3.0), and 4.1 (2.2-7.9) per 100-PY for SARS-COV-2 infections. A total of 8,058, 2,114 and 977 DLBCL patients were included in 1L, 2L, and 3L+ cohorts, respectively. The EAIR of infections resulting in hospitalization in 1L, 2L, and 3L+ cohorts were 64.2 (60.7-67.8), 85.2 (76.9-94.3), and 113.4 (98.4-130.7) per 100-PY for any infection; and 6.3 (5.5-7.2), 7.3 (5.6-9.6), and 15.1 (11.3-20.2) per 100-PY for SARS-COV-2 infections respectively. The EAIR of fatal hospitalizations were 12.0 (10.8-13.3), 23.0 (19.5-27.1), and 27.8 (22.1-34.9) per 100-PY for any infection; and 1.6 (1.2-2.1), 2.7 (1.7-4.2), and 4.8 (2.9-8.0) per 100-PY for SARS-COV-2 infections in 1L, 2L and 3L+ cohorts, respectively. Conclusions: This real-world analysis demonstrated substantial morbidity and mortality associated with overall and SARS-COV-2 infections among NHL patients, with a higher incidence in DLBCL compared to FL, and with increasing LoTs.
Impact of military deployment on non-Hodgkin lymphoma subtype.
Authors: Robert Sgrignoli, Matthew Rendo, Joshua L. Fenderson, Michael Morris, Chung-ting Jimmy Kou, James Aden, Christin DeStefano
Journal: Journal of Clinical Oncology (2024)

e19070 Background: Approximately 3.5 million activity duty service members (ADSM) have deployed to Afghanistan or Iraq from 2001-2022. During deployments, ADSMs are potentially exposed to deployment-related toxins and carcinogens, which could theoretically alter cancer biology. In terms of non-Hodgkin lymphoma (NHL), it is unclear whether deployment affects NHL subtype or cancer-specific survival. Methods: Deployment and occupation data from the Defense Manpower Data Center was merged with data from the Department of Defense Tumor Registry. Documented cases of NHL diagnosed from 2001-2022 were identified. ADSMs and retirees were included; dependents and those under the age of 18 were excluded. Differences in NHL subtype (aggressive B-cell, indolent B-cell, T-cell) and cancer-specific survival were assessed by deployment status (previously deployed vs. never deployed). Occupation was assessed among those who deployed. Propensity score matching (2:1) for age at diagnosis, year of diagnosis, and gender was performed to minimize confounding. All data were carried out using SAS and Jump statistical software. This study was approved by the IRB. Results: There were 2,599 ADSMs and retirees diagnosed with NHL between 2001-2022. Approximately 15% had previously deployed (n=398). Compared with never deployed, military personnel who had previously deployed were more likely to have aggressive B-cell NHL (45% vs. 34%) and less likely to have indolent B-cell NHL (50% vs. 54%) or T-cell NHL (6% vs. 12%), p&lt;0.001. Deployment to Iraq or Afghanistan did not impact NHL subtype. During deployment, occupations of Infantry, Engineering and Healthcare did not impact NHL subtype, whereas occupations of Pilot/Aircrew and Intelligence did, with less T-cell lymphoma diagnosed (0 vs. 7%, and 3% vs. 8%, respectively). When evaluating NHL subtype by race, it was noted that in comparison to White, Asian, Pacific Islander and Other Race, Black Race was associated with more T-cell NHL (21%), largely comprised of cutaneous T-cell lymphoma. Conclusions: After propensity score matching, prior deployment was associated with more aggressive B-cell lymphoma than military personnel who had never deployed. Deployment occupation affected NHL subtype diagnosed, with Pilots/Aircrew and Intelligence personnel being less likely to have T-cell lymphoma, whereas Black Race was associated with a higher likelihood of having T-cell lymphoma. This study sheds insights into the impact of deployment on cancer subtype. Ongoing investigations are assessing mortality differences by deployment as well as causes of death.
Phase 3 trial evaluating the efficacy and safety of odronextamab versus investigator’s choice in previously untreated follicular lymphoma (OLYMPIA-1).
Authors: Ruemu Ejedafeta Birhiray, Stefano Luminari, Tae Min Kim, Münci Yağcı, Timothy Robert Wassenaar, Ashish Risal, Manjusha Namuduri, Jingxian Cai, Bertha Fearon-Chalet, Min Zhu, Sushmita Mukherjee, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth R Ambati, Umberto Vitolo
Journal: Journal of Clinical Oncology (2024)

TPS7096 Background: Follicular lymphoma (FL) is an incurable disease in which patients will relapse despite the effectiveness of first-line (1L) rituximab-based chemoimmunotherapy (CIT), indicating the need for alternative 1L treatments that can deepen and prolong response. Odronextamab, an off-the-shelf, CD20×CD3 bispecific antibody, showed compelling efficacy and generally manageable safety as a monotherapy at 3L+ for patients with relapsed/refractory (R/R) FL in the Phase 2 ELM-2 study (Villasboas, et al. ASH 2023). Objective and complete response (CR) rates were 80% and 73%, respectively, median duration of response was 22.6 months, median progression-free survival (PFS) was 20.7 months, and median overall survival was not reached. The rate of treatment-related adverse events leading to treatment discontinuation was 7.8%. The activity of odronextamab monotherapy in this heavily pretreated R/R FL population, including among patients with rituximab-refractory disease, provides a strong rationale for developing odronextamab as a chemotherapy-free option that can improve long-term outcomes in 1L. Methods: OLYMPIA-1 (NCT06091254) is a Phase 3, randomized, open-label, multicenter study of odronextamab versus investigator’s choice of CIT (R-CHOP, R-CVP, or R-bendamustine) in patients with previously untreated FL. The study consists of Part 1 (safety run-in), followed by Part 2 (randomization). In Part 1, patients will receive six 21-day cycles (induction) of intravenous odronextamab, administered in a step-up regimen during Cycle (C) 1 to mitigate the risk of cytokine release syndrome, followed by full dose starting from C2. Patients with CR or partial response at the end of induction will receive 12 doses of odronextamab maintenance given Q8W. In Part 2, patients will be randomized 1:1 to receive induction of six cycles of odronextamab followed by odronextamab maintenance, or CIT followed by rituximab maintenance. Key inclusion criteria: aged ≥18 years; CD20+ FL Grade 1–3a, stage II bulky or stage III/IV; measurable disease; and ECOG performance status 0–2. Patients with central nervous system lymphoma or histological Grade 3b are excluded. The Part 2 primary endpoint is CR at 30 months (CR30) as assessed by independent central review. Key secondary endpoints include PFS, event-free survival, investigator-assessed CR30, and patient-reported outcomes. Biomarkers (including minimal residual disease by ctDNA) will be evaluated as exploratory endpoints. This trial is currently recruiting and is expected to enroll ~12–32 patients in Part 1 and ~446 patients in Part 2 at ~200 global sites. Clinical trial information: NCT06091254 .
Post-ASCT consolidation with EPD or ERD in patients with high-risk multiple myeloma.
Authors: Eli Zolotov, Maciej Kabat, Harsh Parmar, Palka Anand, Josh Zenreich, Adolfo Aleman, Pooja Phull, David H. Vesole, David Samuel DiCapua Siegel, Noa Biran
Journal: Journal of Clinical Oncology (2024)

7534 Background: Patients (pts) with high-risk (HR) Multiple Myeloma (MM), characterized by at least two cytogenetic abnormalities often experience rapid disease progression and early relapse post-autologous stem cell transplant (ASCT) with median Progression-Free Survival (PFS) of 24 or 12 months with or without lenalidomide maintenance (Panopoulou et al, Blood 2023). This study assesses the efficacy and safety of EPD (Elotuzumab, Pomalidomide, Dexamethasone) or ERD (Elotuzumab, lenalidomide , Dexamethasone) as consolidation therapy post-ASCT in HR MM pts. Methods: In this single-center retrospective study, we reviewed records of MM pts treated with consolidative ERD or EPD from September 2016 to March 2023. We collected baseline MM characteristics, treatment history, adverse events (AEs), and survival outcomes. HR MM pts were defined by 2 or more cytogenetic abnormalities (del 17p, 1q21 gain or amplification, t(14;16), t(14;20), complex karyotype) and/or high-risk gene expression profiling scores (GEP, SKY92). All patients, aged ≥21, underwent ≥1 full cycle of EPD or ERD post-ASCT, administered for a total of four 28-day cycles, following the standard dosing regimen with a rapid dexamethasone taper over the last two cycles. Results: A total of 78 HR MM pts, median age 64 years with 51.2% males and 71.7% caucasians were included. Of them, 62 pts received ERD and 16 received EPD. FISH revealed 62.7% of pts had 2 or more high risk cytogenetic abnormalities. Other pts expressed a combination of cytogenetic abnormalities and/or high-risk GEP or SKY92 scores. The table shows improvement in MRD negativity rates from 21.7% to 26.9% pre and post consolidation, and in VGPR or better from 78.2% to 85.8%. Median PFS for all pts, defined from the time of ASCT to disease progression, was 26.9 months. Most common adverse effects were anemia (71.7%), fatigue (55.1%) and thrombocytopenia (51.2%). Five patients experienced grade 3 adverse events, including 3 with infectious etiology (3.8%) and 2 with immune-mediated toxicity (2.5%). No treatment-related serious adverse events were reported. Conclusions: Four cycles of EPD or ERD consolidation therapy post-ASCT, demonstrated promising efficacy in HR MM pts. The observed median PFS of 26.9 months was comparable to that seen with chronic lenalidomide maintenance and superior to patients who do not receive lenalidomide maintenance. The improvement in PFS was achieved with a fixed duration rather than continuous therapy and without lenalidomide-associated toxicities such as secondary malignancies, chronic diarrhea, and financial toxicity. Further prospective confirmatory studies are needed. [Table: see text]