bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the impact of demographic disparities on clinical outcomes in cutaneous T-cell lymphoma (CTCL): A multicenter retrospective cohort analysis.
Authors: Niyogusaba Tim , Switchenko Jeffrey M. , Rozati Sima , Iyer Swaminathan Padmanabhan , Talluru Sai , Huen Auris , Greenwell Irl Brian , Scribner Jane , Rangarajan Sunil , Mehta Amitkumar , Beaven Anne , Bhatti Safiyah , Krishanasamy Shalini , Porcu Pierluigi , Sethi Tarsheen , Foss Francine M. , Paulino Darina , Case Katherine , Lechowicz Mary Jo , Allen Pamela Blair 
Published: June 2023

7573 Background: Black patients have been shown to have a higher incidence of cutaneous T-cell lymphomas (CTCL) and display unique clinicopathologic features at diagnosis, however, drivers of these disparities and the role of social determinants of health (SDoH) remain poorly understood. Methods: To further characterize the prognostic relevance of racial and demographic disparities in CTCL, we performed a retrospective review of 1,198 patients seen at 8 different academic treatment centers in the United States between 2000-2020. Clinical variables included demographics, disease characteristics, and survival. Race and ethnicity were stratified into 2 groups for this analysis: non-Hispanic Black (B) and Non-Black (NB). Distance to center was stratified into short, intermediate, or long commute ( < 10, 10-50, > 50 miles, respectively) based on home zip code. The primary endpoint was overall survival (OS). Univariate association and multivariable analyses were assessed using Cox proportional hazards models. Results: Among 1,198 total patients, 42.4% identified as B and 58.6% as NB. B patients presented younger, had a shorter commute, lower income, but no difference in insurance compared to NB patients. There was no difference in survival by race (Median OS 74 months (95% CI 65-84) compared to 65 (95% CI 58-75) for NB patients). Distance to center was strongly associated with survival and remained significant on multivariate analyses after controlling for age, race, and other SDoH. Longer commute was associated with worse OS compared to short commute for both B and NB counterparts (median 55 months [95% CI 49-66] vs. 79 [95% CI 69-90] and 75 [95% CI 63-86], respectively, p = 0.006). Conclusions: We characterized the impact of race and SDoH on overall survival (OS) in a diverse, multicenter cohort of patients with CTCL. We found that distance to cancer center was the most important factor contributing to disparities in OS in this study. This highlights the importance of improving access to care, particularly in rare and clinically heterogeneous diseases such as CTCL.
CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma.
Authors: Lin Yi , Martin Thomas G. , Usmani Saad Zafar , Berdeja Jesus G. , Jakubowiak Andrzej J. , Agha Mounzer E. , Cohen Adam D. , Deol Abhinav , Htut Myo , Lesokhin Alexander M. , Munshi Nikhil C. , O'Donnell Elizabeth , Jackson Carolyn Chang , Yeh Tzu-min , Banerjee Arnob , Zudaire Enrique , Madduri Deepu , delCorral Christopher , Bubuteishvili-Pacaud Lida , Jagannath Sundar 
Published: June 2023

8009 Background: Heavily pretreated patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with standard of care therapy have median overall survival (OS) of ~12 months (mo). In the single-arm, phase 1b/2 CARTITUDE-1 study (NCT03548207), pts received a single infusion of ciltacabtagene autoleucel (cilta-cel), a CAR-T cell therapy targeting BCMA. At the final protocol-specified analysis (27.7-mo median follow-up [MFU]), overall response rate (ORR) was 98%, with 83% stringent complete response (CR); 27-mo rates of progression-free survival (PFS) and OS were 55% and 70%, respectively. Here, we report study closeout results. Methods: Eligible pts received ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD); and had received prior PI, IMiD, and anti-CD38 antibody therapy. Primary endpoint was ORR and safety; secondary endpoints included PFS, OS, and minimal residual disease (MRD) negativity at 10-5. Results: 97 pts received cilta-cel (median age 61 years [y]; median 6 prior LOT; 42% penta-drug refractory; 88% triple-class refractory; 99% refractory to last LOT). As of October 14, 2022, MFU was 33.4 mo (range, 1.5-45.2). Median (m) duration of response was 33.9 mo (95% CI, 25.5–not estimable [NE]). mPFS was 34.9 mo (95% CI, 25.2–NE), with an estimated 47.5% progression free and alive at 36 mo. mOS was not reached (NR), with an estimated 62.9% survival at 36 mo. Of 49 MRD-evaluable pts, 26 had MRD negativity sustained for ≥12 mo, of which 20 had sustained MRD-negative ≥CR. mPFS was NR in these subgroups (Table). 18 pts were MRD negative with ≥CR at 24 mo post infusion. No new safety signals and no new neurotoxicity events were reported since the 27.7-mo MFU. 6 new cases of second primary malignancy were reported, including 2 cases of basal cell carcinoma and 1 case each of myelodysplastic syndrome, B-cell lymphoma, melanoma, and prostate cancer. 5 additional deaths occurred (progressive disease [PD], n=3; pneumonia and sepsis, n=1 each [both unrelated to cilta-cel]), for a total of 35 (PD, n=17; unrelated to cilta-cel, n=12; related, n=6). Conclusions: Longer mPFS was observed after a single infusion of cilta-cel than any previously reported therapy in heavily pretreated pts with RRMM. Achieving CR and/or sustained MRD negativity was associated with prolonged PFS. Pts continue to be followed for safety and survival in the 15-y CARTINUE long-term study (NCT05201781; MMY4002). Clinical trial information: NCT03548207 . [Table: see text]
Safety and efficacy of standard of care (SOC) ciltacabtagene autoleucel (Cilta-cel) for relapsed/refractory multiple myeloma (RRMM).
Authors: Hansen Doris K. , Patel Krina K. , Peres Lauren C. , Kocoglu Mehmet H. , Shune Leyla , Simmons Gary , Ferreri Christopher J. , Atrash Shebli , Parrondo Ricardo Daniel , Chhabra Saurabh , Costello Patrick , Midha Shonali , Alsina Melissa , Voorhees Peter M. , Htut Myo , Sborov Douglas W. , Khouri Jack , Janakiram Murali , Lin Yi , Sidana Surbhi 
Published: June 2023

8012 Background: Cilta-cel was FDA approved in 2022 for the treatment of RRMM. We evaluated the outcomes of patients treated with intended SOC cilta-cel. Methods: 12 US academic medical centers contributed data to this retrospective study. As of 12/31/2022, 177 patients were leukapheresed and 139 received cilta-cel. Results: The table describes the study population compared to the CARTITUDE-1 trial. More patients in our study had extramedullary disease (EMD, 35%) and high-risk cytogenetics (41%). 55% of the patients would not have met eligibility criteria for CARTITUDE-1. Common reasons for ineligibility were cytopenias (19%), prior BCMA therapy (14%), organ dysfunction (12%), oligosecretory disease (13%), and plasma cell leukemia (8%). 83% of the patients received bridging chemotherapy (overall response rate, ORR: 28%). Lymphodepletion included fludarabine (Flu) + cyclophosphamide (Cy): 81%, bendamustine: 11%, Cy: 4%, and cladribine + Cy: 4%. Median CAR-T cells infused were 0.6 million/kg (range: 0.1-0.9), and 19% of patients were treated on an expanded access protocol (EAP). Median follow-up was 2.3 months (range: 0-8). Cytokine release syndrome (CRS) was seen in 81% (≥ grade 3: 7%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (≥ grade 3: 8%) of patients. Tocilizumab, steroids, and anakinra were used in 61%, 44%, and 10% of patients, respectively. Delayed neurotoxicity (NT) was seen in 9% (cranial nerve palsy: 8, Parkinsonism: 2, others: 3). Grade ≥ 3 cytopenias at day ≥ 30 were seen in 75% of patients. Infections were seen in 32% of patients. Day 30 (N=115) and best response rates (N=118) were: ≥ partial response (PR), 75/80%; ≥ very good PR, 44/62%; and ≥ complete response (CR), 26/40%, respectively. In the non-EAP FluCy population (N=88), best ORR/≥CR were 89/49%. 17 patients died by data cut-off, 4 due to disease progression and 13 (9%) due to non-relapse mortality (NRM) (grade 5 CRS: 3, infection: 6, CRS/infection: 1, grade 5 ICANS: 1, delayed NT: 2). Conclusions: Patients treated with intended SOC cilta-cel had a favorable ORR (80%) despite a larger proportion of patients having high-risk features relative to trial patients and limited follow-up. Response rates were higher in patients receiving conforming products with FluCy conditioning (89%). Delayed NT and NRM were seen in 9% of patients. Results will be updated with continued follow-up. D.K.H., K.K.P, M.J., Y.L. & S.S. contributed equally. [Table: see text]
Plasma cell leukemia: A multicenter retrospective study of 150 patients.
Authors: Chineke Iloabueke Gabriel , Wertheim Betsy C. , Roe Denise , Larsen Ashley , Sborov Douglas W. , Vardell Victoria , Green Damian Jonathan , Degraff Dominique , Liedtke Michaela , Okoniewski Maire , Wazir Mohammed , Nadeem Omar , Paquin Shubert Ashley , Silbermann Rebecca Wang , Schachter Levanto Gershon , Coffey David , Schmidt Timothy Martin , Brunner Matthew , Wong Sandy Wai Kuan , Gowin Krisstina L. 
Published: June 2023

8014 Background: Despite the use of novel induction regimens, stem cell transplantation (SCT), and maintenance therapy, plasma cell leukemia (PCL) remains a challenging disease with a dismal prognosis. Currently, there is no agreed standard of care management for PCL. We conducted a multicenter retrospective analysis of the clinical presentation, treatment, and outcomes of 150 patients with PCL. Methods: Data of patients diagnosed with pPCL or sPCL between 01/2010 and 01/2021 were entered into a study-specific REDCap database from 7 different U.S. academic sites. PCL was defined as ≥ 5% circulating plasma cells. Clinical data included baseline patient characteristics, clinical presentation, treatment, therapeutic response, and survival outcomes. Overall survival (OS) curves were plotted using the Kaplan-Meier method. Cox proportional hazards regression tested associations between patient characteristics and OS, generating hazard ratios (HR) and 95% confidence intervals (CI), adjusted for PCL type (primary or secondary) and SCT. Results: The analytical cohort included 93 pPCL and 57 sPCL patients. Median age at diagnosis was 60 years. High-risk cytogenetics were found in 56.7% of the patients where it was documented. Of the 79 patients with a documented induction regimen, 58.2% received a proteasome inhibitor triplet, 22.8% received a VTD-Pace like conventional chemotherapy, and 3% received a daratumumab quadruplet regimen. SCT (autologous or allogeneic) was done in 56.1% of the patients. The median OS for all patients, those with pPCL, and those with sPCL was 20.3, 36.6, and 3.2 months, respectively. Secondary PCL was associated with worse survival outcomes compared with pPCL (HR, 2.46; 95% CI, 1.51-3.98; p<0.001) (Table). Median OS was better in patients treated with a proteasome inhibitor triplet regimen vs VTD PACE-like combination (28.2 versus 12.6 months). OS was prolonged among patients who underwent any type of SCT compared with those who did not undergo SCT (44.0 versus 5.7 months, p<0.001). Conclusions: This multicenter retrospective study is one of the largest PCL analyses performed to date and reveals the clinical practice patterns of treatment and survival of PCL patients across the U.S. in the novel treatment era. The survival analysis reinforces the poor prognosis in sPCL patients and the continued need for novel treatment approaches in this patient population. While limited by retrospective design, this analysis suggests prolonged survival with transplantation in both pPCL and sPCL. [Table: see text]
Disparities in multiple myeloma: A global perspective on drug toxicity trends.
Authors: Jaberi-Douraki Majid , Xu Xuan , Faiman Beth , Wyckoff Gerald , Riviere Jim , Khouri Jack , Mazzoni Sandra Ann , Ramachandran Remya Ampadi , Gadara Nuwan Millagaha , Golmohammadi Mobina , Williams Louis , Samaras Christy Joy , Valent Jason Neil , Anwer Faiz , Raza Shahzad 
Published: June 2023

8015 Background: The FDA Adverse Event Reporting System (FAERS) is one of the largest pharmacovigilance databases containing information on adverse events (AEs) received from manufacturers, consumers and healthcare professionals. The purpose of this study is to evaluate the global disparities in multiple myeloma (MM) through data mining of FAERS. Methods: We examined AEs associated with FDA-approved MM drugs from 2003-2022 from FAERS and the Medical Dictionary for Regulatory Activities. Patient data were then stratified based on age, sex (F/M) and 6 geographical regions. We evaluated the reporting odds ratio (ROR) combined with a 95% confidence interval for the elevated incidence of AEs. Results: The data curation provided 381,378 patients with information from North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC) and Latin America & the Caribbean (LA), merged from 129 countries and 27 phenotypic systems and organs categories when the number of AEs happened more than 0.1% of the total. Cardiotoxicities (n=23160) and vascular toxicities (n=26716) were seen more in NA (M) (ROR=1.16±0.02 and EU (M) (ROR=1.11± 0.03) compared to the rest of the World. Nephrotoxicity (n=17486) was reported more in AF (M) (ROR=2.92±0.41) compared to AS (M) (ROR≥1.17± 0.12), EU (M) (ROR≥1.34± 0.13) and NA (M) (ROR=1.09± 0.03). Peripheral neuropathies (n=14786) were frequent among EU (F) (ROR=1.09±0.07) and OC (M) (ROR=1.08± 0.04). Mortality was higher among AS and EU (ROR≥2.15± 0.93) compared to NA and OC. There were 18,222 secondary neoplasms in FAERS. Skin neoplasms (n=4650) more frequently occurred in OC and EU (ROR≥1.70 ±0.16). Breast neoplasms (n=694) were the highest in EU (F) (ROR=4.01+0.63) and lowest in OC (F) (ROR<1). Gastrointestinal neoplasms (n=1564) were more common among AS, EU and OC (M) with (ROR≥2.23±0.47). Lymphomas (n=542) were predominant in AS(M) (ROR=2.21±0.98) and OC (M) (ROR=3.35±2.23). Leukemias (n=3896) cases were significantly higher in EU (M) (ROR=4.08 ± 0.40) and EU (F) (3.11 ± 0.26). Respiratory tract and mediastinal neoplasms (n=796) were more common in AS, EU and OC(M) where ROR≥1.36±0.33. More phenotypic characterization are tabulated below. Conclusions: FAERS can be used to assess cancer disparity from a global perspective. Our results indicates that certain AEs are influenced by gender and geographical location. These disparities in MM AEs may be the result of factors such as genetics, dosing/regimen, comorbidities, age and sex. These variables must be investigated for improved patient care, strategies for AE reduction, mortality reduction and optimal allocation of healthcare resources. [Table: see text]
Analysis of infections and parameters of humoral immunity in patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with talquetamab (tal) monotherapy in MonumenTAL-1.
Authors: Rodríguez-Otero Paula , Schinke Carolina D. , Chari Ajai , Lipe Brea , Lavi Noa , Rasche Leo , Vishwamitra Deeksha , Skerget Sheri , Verona Raluca , Ma Xuewen , Khedkar Sheetal , Hilder Brandi , Masterson Tara J. , Campagna Michela , Renaud Thomas , Tolbert Jaszianne A. , Heuck Christoph , Smit Marie-Anne Damiette , van de Donk Niels W.C.J. 
Published: June 2023

8020 Background: Infection, a key complication of MM, may be due to patient, disease, or treatment-related factors. Immunotherapies that impact normal immune cells may increase risk of infection. Tal, a bispecific antibody with clinical benefit in pts with RRMM, targets G protein–coupled receptor family C group 5 member D (GPRC5D), a protein of unknown function with significantly higher expression on malignant versus normal plasma cells. We report the infection profile and immune function with tal in the phase (ph) 1/2 MonumenTAL-1 study (NCT03399799/NCT04634552). Methods: Pts had RRMM, were intolerant to/progressed on established therapies (ph 1), or had ≥3 prior lines of therapy (ph 2; ≥1 proteasome inhibitor/immunomodulatory drug/anti-CD38 antibody). Subcutaneous tal was given at 0.4 mg/kg QW or 0.8 mg/kg Q2W. Infections (graded by CTCAE v4.03) were treated per local guidelines. B-cell subpopulations and IgG levels were assessed from whole blood and serum samples, respectively. Results: We evaluated 339 pts on tal QW or Q2W, of whom 51 had prior T-cell redirection therapy (pTCRT); infection rates are shown in the table (median follow-up, 15.9, 10.1, and 13.1 mo, respectively). New-onset infections were most prevalent during cycles 1–2. Grade (gr) 3/4 infections observed in >2 pts were pneumonia (3.5%) and UTI (2.1%) on tal QW; pneumonia (2.1%) and COVID-19 (2.1%) on tal Q2W; and pneumonia (5.9%) with pTCRT. Opportunistic infections were observed in 3.5%, 4.1%, and 5.9% of pts, respectively. Less than 1.5% of pts died from infections: COVID-19 pneumonia (n=2) and one each due to septic shock, fungal sepsis, and unknown etiology. Hypogammaglobulinemia rates by IgG values were 64.3% (tal QW), 65.5% (tal Q2W), and 70.6% (pTCRT); IVIg use was 14.7%, 12.4%, and 15.7%, respectively. CD19+ B-cell levels were stable, and there was a trend toward increased non-clonal IgG over time. Conclusions: Roughly 20% of pts had gr 3/4 infections on tal (most frequently cycles 1–2), with low rates of opportunistic infections, discontinuation, and death. Infection rates, particularly rates of fatal infections, appear lower with tal than with BCMA-targeted T-cell–based therapies. A trend toward increased non-clonal IgG suggests potential recovery of humoral immunity accompanies rapid, deep, and durable responses to tal. These results distinguish tal as an important emerging therapy for RRMM. Clinical trial information: NCT03399799 , NCT04634552 . [Table: see text]
Prognostic value of month 1 bone marrow and PET MRD status in CAR-T therapy for myeloma.
Authors: Bansal Radhika , Babcock Jeffrey , Brunaldi Larissa , Chhabra Saurabh , Parrondo Ricardo Daniel , Gertz Morie A. , Hathcock Matthew , Dingli David , Kapoor Prashant , Kourelis Taxiarchis , Cook Joselle , Hayman Suzanne R. , Warsame Rahma M. , Binder Moritz , Fonseca Rafael , Bergsagel Peter Leif , Ailawadhi Sikander , Kumar Shaji , Broski Stephen M , Lin Yi 
Published: June 2023

8024 Background: Minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). MRD is usually assessed in the bone marrow (BM) by flow cytometry or NGS. MRD by FDG PET/CT provides a global representation of the tumor burden, including response assessment of extramedullary disease. We examined MRD status in MM pts using both BM and PET/CT at Mayo Clinic. Methods: Medical records were reviewed retrospectively for MM pts who received CAR-T between 4/2018 and 12/2022. All PET/CT scans were assessed by radiologists. BM MRD was assessed by flow cytometry with a sensitivity of 10-5. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Results: Among the 157 CAR-T pts, including 89 pts who received FDA-approved CAR-T, median age was 63 years, 59% (92/157) were males, 42% (66/157) had high risk cytogenetics with median of 5 prior lines of therapy, 36% (57/157) had plasmacytoma. Incidence of CRS was 83%, 5% grade ≥ 3 CRS. Incidence of ICANS was 19%, 4% grade ≥ 3 ICANS. CR/sCR rate was 37%. One hundred and thirty-seven pts (87%) had evaluable BM at month (mo) 1, 85% (117/137) were BM MRDneg at mo 1. Baseline demographics were comparable between the two groups except age, % BM plasma cells and use of bridging therapy. Among the MRDneg pts, CR/sCR rate was 44% (51/117) and 95% (111/117) had sFLC below normal. At median follow-up of 13.8 months, median PFS among pts with BM MRDneg at 1 mo was 12 mo (95% CI: 11, 30) vs 3 mo (95%CI: 2, 7) for BM MRDpos (p<0.001). Median OS among pts with BM MRDneg at 1 mo was 34 mo (95% CI: 24, NR) vs 22 mo (95%CI: 7, NA) for BM MRDpos (p<0.01). At month 1, 112 pts had both BM and PET/CT assessments available, 64/112(57%) were both BM MRDneg/PET MRDneg, 38/112 (34%) were MRDneg for either BM or PET and 10/112 (9%) were positive for both BM and PET (MRDpos/PET MRDpos). Baseline demographics except age were comparable between the 2 groups (Table). Rate of conversion from MRDpos to MRDneg was low. Rate of sustained BM and PET MRDneg at mo 12 was 44% (8/18). The median PFS and OS for BM MRDneg/PET MRDneg was significantly longer as compared to others (Table). Conclusions: Achieving FLC below normal, BM MRDneg and PET MRDneg at 1 month, regardless of IMWG response at that time, is prognostic for both PFS and OS in MM pts receiving CAR-T. Failure to achieve any of these confers poor prognosis. [Table: see text]
Population pharmacokinetic-pharmacodynamic model of nirogacestat effects on B-cell maturation antigen in healthy subjects.
Authors: Shearer Todd , Williams Rex L. , Johnson Mark , Cendrowicz Ewa , Leonowens Cathrine , Smith Margaret , Baughman Todd , Breitbach Caroline J. , Smith L. Mary , Cheng Shinta 
Published: June 2023

8027 Background: B-cell maturation antigen (BCMA) is expressed on the membrane of normal plasma cells (PCs) and multiple myeloma (MM) cells and is the target of several investigational agents and approved products for MM treatment. Mechanistically, BCMA is cleaved from the cell surface by the enzyme gamma secretase, resulting in reduced levels of membrane-bound BCMA (mbBCMA) and release of soluble BCMA. Gamma secretase inhibitors (GSIs) have been shown to increase BCMA receptor density and potentiate the activity of several BCMA-targeted therapies in both clinical trials and in vitro studies. Although the effect of GSIs on BCMA receptor density has been well characterized in vitro, their effect on BCMA dynamics is incompletely understood in humans. This study sought to evaluate the pharmacodynamics (PD) of the GSI nirogacestat on mbBCMA in healthy subjects. Methods: A total of 23 healthy subjects were administered single doses of 50, 150, or 300 mg nirogacestat or multiple doses of 100 mg every 12 hours. Density of mbBCMA on PCs isolated from whole blood and bone marrow was measured by flow cytometry at baseline and 1, 2, 4, 8, 24, and 48 hours after single doses and 24 and 48 hours after the first dose in subjects receiving multiple doses. Nirogacestat serum concentrations were also measured at multiple time points to fully characterize the pharmacokinetics (PK). A population PK-PD model of the effect of nirogacestat on BCMA dynamics in humans was developed and used to simulate various administration dose levels and schedules to find an optimal nirogacestat regimen that continually increases mbBCMA over the dosing interval. Results: A 2-compartment model with linear absorption and elimination described serum nirogacestat in healthy subjects. A sequential PK-PD model that included an effect compartment and drug effect on mbBCMA cleavage rate described mbBCMA values. Simulations indicated that a 100-mg dose administered twice daily sufficiently maintained elevated and clinically relevant mbBCMA levels. Exposure and efficacy benchmarks from in vitro experiments and published clinical studies were used to contextualize simulations and hypothesize various dose and schedule scenarios to minimize dose of the BCMA-targeting therapy while maximizing BCMA potentiation. Conclusions: These results suggest that nirogacestat dose and schedule may have direct implications on the potentiation of BCMA-targeting therapies. Simulations suggest that the 100-mg, twice-daily nirogacestat dose results in elevated mbBCMA levels that could even allow for use of lower doses of BCMA-targeted agents while maintaining or improving efficacy. Study results along with this PK-PD model will be used to support nirogacestat dose and schedule in ongoing and planned studies in patients with MM.