bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and ethnic disparities in risk of second primary malignancies among diffuse large B-cell lymphoma survivors.
Authors: Advani Pragati Gole , Attwood Kristopher , Herr Megan , Ba Aqeel Sheeba Habeeb , Torka Pallawi 
Published: June 2023

7567 Background: Previous studies have shown an increased risk of second primary malignancies (SPMs) among diffuse large B-cell lymphoma (DLBCL) survivors; however, this has not been comprehensively examined by race/ethnicity. We utilized a large population-based database to examine disparities in SPM risk by race/ethnicity. Methods: From 17 United States population-based Surveillance, Epidemiology and End Results (SEER) program cancer registry areas, we identified 57,262 ≥12-month first-primary DLBCL survivors diagnosed between 2000-2019. Standardized incidence ratios (SIRs) and accompanying 95% confidence intervals (CIs) quantified SPM risk by race/ethnicity (non-Hispanic White, Black, Asian/Pacific Islander [API] and Hispanic), compared with the general population. Results: Overall, we observed 4,719 SPMs after DLBCL representing a 1.2-fold significantly increased risk (95% Confidence Interval [CI] = 1.16-1.23) compared to the general population and an excess of 23 cases per 10,000 person-years. SIRs for all second cancers combined varied significantly by race/ethnicity with APIs and Hispanics presenting higher overall SPM risk [SIRAPI: 1.42 (CI = 1.27-1.59), and SIRHispanic: 1.31 (CI = 1.19-1.43)] compared to the White or Black patients [SIRwhite: 1.17 (CI = 1.13-1.21), SIRBlack: 1.16 (CI = 1.03-1.30)] (p-heterogeneity < 0.001). Heterogeneity by race/ethnicity in SIRs was even more pronounced in DLBCL survivors diagnosed at a younger age, those who were ≥5 years into their survivorship, those who had received chemotherapy, or those who had received no radiation as their initial treatment. Although SIRs for SPM was significantly higher for advanced stage DLBCL survivors (compared to those with a localized/regional disease), heterogeneity by race/ethnicity in SPM risk was significant regardless of the stage. Results from site specific analyses reported significantly higher overall SIRs for second hematological malignancies compared to solid cancers [SIRhemat: 3.52 (CI = 3.22-3.85), and SIRsolid: 1.08 (CI = 1.04-1.11)]. Patterns by race/ethnicity also varied significantly by second cancer type, particularly for second primary anal cancer, Hodgkin’s lymphoma (HL), and Acute Non-Lymphocytic Leukemia (ANLL) (p < 0.001 for each). Strikingly elevated SPM risks (SIRs > 10) were observed for second primary anal cancer, HL and ANLL among the Black patients, and HL among the APIs and Hispanic DLBCL survivors, compared to the white patients. Conclusions: Using a large-scale population-based data, we observed substantial disparities in SPM risk by race/ethnicity, with patients belonging to minority groups experiencing higher risks. SPMs have emerged as an important challenge for DLBCL survivors, therefore, further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.
Uncertainty and coping in patients with newly diagnosed indolent non-Hodgkin’s lymphoma (iNHL).
Authors: Newcomb Richard , Johnson Patrick Connor , Yang Daniel , Amonoo Hermioni L. , Dhawale Tejaswini More , Chen Yi-Bin Albert , El-Jawahri Areej 
Published: June 2023

7568 Background: iNHLs are a heterogenous group of incurable diseases with prolonged illness courses requiring intermittent periods of surveillance and treatment. Due to illness uncertainty, patients with iNHL struggle with immense psychological distress. Yet, studies exploring coping, prognostic uncertainty and distress in this population are limited. Methods: We conducted a cross sectional study of adults (age ≥ 18) newly diagnosed with iNHL at a single academic center. We enrolled consecutive patients who were diagnosed ≤ 3 months prior to study enrollment. At baseline, we collected patient reported outcomes to assess QOL (Functional Assessment of Cancer Therapy), psychological symptoms (Hospital Anxiety and Depression Scale), prognostic understanding (Prognostic Awareness Impact Scale), and coping (Brief COPE). We categorized coping as approach-oriented (active coping, use of emotional support, positive reframing, acceptance) and avoidant (behavioral disengagement, denial, and self-blame). We used median split to differentiate between low and high utilizers of approach or avoidant coping. Results: We enrolled 70.6% (48/68) of eligible patients newly diagnosed with iNHL (mean age 66.8 yrs; 39.6% chronic lymphocytic leukemia/ lymphoma; 33.3% follicular lymphoma). At baseline, nearly one-third (31.2%) experience clinically significant symptoms of anxiety and depression. 45.8% of patients identified prognostic uncertainty as the “the most stressful part of being a patient,” and 31.2% reported having “difficulty letting go of thoughts about their prognosis.” Notably, patients had significant misperceptions about their prognosis with incurable iNHL, as 47.9% reporting that a cure was at least ‘somewhat’ likely. Patients with iNHL most often used acceptance (56.3%), denial (47.9%), and emotional support (47.9%) as coping strategies. Patients who were high utilizers of multiple approach-oriented coping strategies experienced fewer anxiety (B = -2.66, p = 0.01) and depression (B = -1.73, p = 0.02) symptoms and improved QOL (B = 9.43, p = 0.001). Patients who highly utilized any avoidant-oriented coping strategies experienced increased anxiety symptoms (B = 2.16, p = 0.05), but no difference in depression symptoms or QOL. Conclusions: Patients with iNHL report immense prognostic uncertainty and psychological distress. Use of multiple approach oriented coping strategies was associated with decreased psychological distress and improved QOL. Interventions to address prognostic uncertainty and to promote approach oriented coping in patients with iNHL are sorely needed and have the potential to ameliorate psychological distress and improve QOL in this vulnerable population.
Preliminary data of a phase 1b/2 study of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).
Authors: Ailawadhi Sikander , Lasica Masa , Fu Chengcheng , Thomas Sheeba K. , Wu Depei , Yi Shuhua , Siddiqi Tanya , Yin Qingsong , Allan John N. , Chen Wenming , Matous Jeffrey V , Feng Ru , Chen Zi , Yu Min , Li Mingyu , He Zicong , Ahmad Mohammad , Wang Hengbang , Chanan-Khan Asher Alban Akmal , Zhai Yifan 
Published: June 2023

7569 Background: B-cell lymphoma 2 inhibitors (BCL-2i) are well tolerated and effective in treating B-cell lymphoproliferative disorders such as CLL. Investigational agent lisaftoclax is a novel, oral, highly selective and potent BCL-2i. Preclinical data show a strong synergistic effect of lisaftoclax plus ibrutinib in an ibrutinib-insensitive PDXWM1 model. Methods: This global, open-label, multicenter study evaluates the safety and efficacy of lisaftoclax alone and combined with ibrutinib or rituximab in pts with WM. Pts were enrolled in 3 arms: Arm A (lisaftoclax), BTKi-resistant/intolerant pts; Arm B (lisaftoclax plus ibrutinib), treatment-naïve pts; and Arm C (lisaftoclax plus rituximab), BTKi-naïve relapsed/refractory pts. Lisaftoclax was escalated from 400 to 1,200 mg using a modified toxicity probability interval design. A 3-day ramp-up was used for pts at high TLS risk. Primary objectives were pharmacokinetics (PK), safety, and efficacy assessments; responses were assessed per IWWM criteria. Results: As of January 25, 2023, 46 pts were enrolled (Arm A [n = 14]; up to 1,000 mg; Arm B [n = 24]; up to 1,200 mg; Arm C [n = 8]; up to 800 mg). Baseline characteristics are shown in the table. Median (range) treatment duration was 6 (1-18; Arm A), 14 (1-27; B), and 8 (2-26; C) months. Overall response rates (ORRs) were: Arm A, 25% (median time to response [MTTR], 4.3 months); Arm B, 90.9% (MTTR, 1.9); Arm C, 37.5% (MTTR, 4.4). No significant difference was observed between pts with and without CXCR4-mut. At 1,200 mg, 1 DLT (grade 3 clinical TLS), due to pre-existing renal impairment, was reported. At 1,000 mg, 1 grade 3 laboratory TLS occurred in Arm B because of dehydration and active symptomatic therapies; abnormal electrolytes resolved after 1 day of drug interruption, without recurrence. Grade ≥ 3 lisaftoclax-related AEs included neutropenia (13%), leukocytopenia (4.3%), anemia (2.2%), weight loss (2.2%), and septic shock (2.2%). Ventricular arrhythmias were not observed. Only 1 pt required dose reduction (due to neutropenia). MTD has not been reached. A total of 14 pts discontinued study treatment because of disease progression (n = 5) and AE (n = 1). Lisaftoclax plus ibrutinib showed a PK exposure comparable to ibrutinib alone, indicating no potential DDI. Conclusions: Lisaftoclax alone or combined with ibrutinib/rituximab demonstrated measurable effects in pts with naïve or BTKi-treatment-failed WM. Internal study identifier: APG2575WU101. *SA and ML are co-first authors. Clinical trial information: NCT04260217 . [Table: see text]
Epidemiologic characteristics, treatment patterns, and survival analysis of plasmablastic lymphoma in the US.
Authors: Hansen Alec , Vardell Victoria , Fitzgerald Lindsey 
Published: June 2023

7570 Background: Plasmablastic Lymphoma (PBL) is a rare aggressive subtype of diffuse large B-cell lymphoma primarily affecting the immunocompromised, including those living with HIV. There is no established standard of care, and current survival estimates range from 8-15 months (mos). With the largest previous study of PBL limited to 590 patients (pts), we aimed to evaluate epidemiologic characteristics, treatment patterns and survival trends on a national scale. Methods: Pts diagnosed with PBL from 2010-2020 were identified in the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program. Age-adjusted incidence rates (IR) were calculated using SEER. Demographic and treatment characteristics and overall survival were evaluated in the NCDB using Kaplan-Meier and multivariate Cox regression analysis. Results: For the 1,153 pts identified in SEER, the incidence of PBL was 0.07 per 100,000 person-years, with higher IR in males (0.12) and pts age > 75 years (0.23). IR increased on average by 4.2% per year from 2010 to 2020 (95% CI 1.51-6.96). Of the 1,822 PBL pts in NCDB, the median age at diagnosis was 57 years. PBL was more common in male (77.2%) and White pts (76.8%). Most pts presented at an advanced (III or IV) Ann Arbor stage (59.9%). Pts were HIV+ in 50.2% of cases and 51.2% had extranodal disease. The median OS (mOS) was 22.4 mos (95% CI 16.2-28.6), with a 1-, 5-, and 10-yr OS of 56%, 40%, 32%, respectively. PBL pts treated with multiagent chemotherapy (N = 862, 66%) had mOS of 58.6 mos (95% CI 43.0-74.3). Pts who received no systemic treatment (N = 456, 25%) had mOS of 1.9 mos (95% CI 1.2-2.5). Pts with Stage I disease had a mOS of 86.2 mos, Stage II of 51.1 mos, Stage III of 35.9 mos, and Stage IV of 8.8 mos. Pts with HIV had a greater mOS (44.0 mos [95% CI 28.7-59.3]) than HIV- pts (21.7 mos [95% CI 12.4-30.9]). On multivariate Cox regression adjusted for age, race, and socioeconomic status, factors associated with worse OS included age (HR 1.03 [95% CI 1.02-1.04], p < 0.001), B symptoms (HR 1.35 [95% CI 1.11-1.65], p = 0.003) and advancing stage. Factors associated with improved OS included Hispanic ethnicity (HR 0.70 [95% CI 0.52-0.93], p = 0.014) and extranodal disease (HR 0.77 [95% CI 0.63-0.93], p = 0.001). HIV+ status had no significant impact on survival (HR 1.09 [95% CI 0.87-1.38], p = 0.443). Conclusions: We present the largest study to date describing the epidemiologic, survival, and treatment patterns of PBL. In contrast to prior studies, we found a longer mOS of 58.6 mos among those treated. This may represent a large real-world population providing more accurate estimates or reflect improved outcomes from a growing number of novel therapeutic options. Notably, HIV+ status did not have a significant impact on OS. While OS remains poor, advances in treatment over the last decade are promising and highlight the need for clinical advances to improve front line therapeutic options for PBL.
Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment of LCAR-B38M CAR-T: At least 5-year follow-up in LEGEND-2.
Authors: Mi Jian-Qing , Zhao Wan-Hong , Chen Li-Juan , Fu Wei-Jun , Wang Bai-Yan , Xu Jie , Liu Jie , Jin Shi-Wei , Zhu Han , Du Juan , Jiang Hua , Sun Huabin , Jia Yehui , Fan Xiao-Hu , Li Jian-Yong , Hou Jian , Chen Zhu , Zhang Wang-Gang , He Ai-Li , Chen Sai-Juan 
Published: June 2023

8010 Background: LCAR-B38M CAR-T cells express a structurally differentiated CAR construct containing a 4-1BB costimulatory domain and 2 BCMA-targeting single-domain antibodies designed to confer avidity. LEGEND-2 was a first-in-human phase 1 study of LCAR-B38M conducted in China, which showed encouraging efficacy and manageable safety in 74 patients (pts) with RRMM. The US phase 1b/2 CARTITUDE-1 and Chinese phase 2 CARTIFAN-1 trials of ciltacabtagene autoleucel, which expresses the same CAR as LCAR-B38M, confirmed the efficacy observed in LEGEND-2. Here, we present ≥5-y FU data from LEGEND-2, the longest FU for any BCMA-targeted CAR-T cell therapy study. Methods: Study design was previously published. Pts underwent lymphodepletion with cyclophosphamide (cy) 300 mg/m2 (n=66) or cy 250 mg/m2 plus fludarabine 25 mg/m2 (n=8) prior to receiving LCAR-B38M at a median dose of 0.51 × 106 (range, 0.07-2.10 × 106) CAR-positive T cells/kg in a single (n=9) or 3 split (n=65) infusions. Results: Pts were enrolled from 30 Mar 2016 to 26 Nov 2017. As of 30 Nov 2022, median FU was 65.4 mo (range, 0.4-78.8). 74 pts had received LCAR-B38M (median age, 54.5 y; 60.8% male; median [range] 3 [1-9] prior lines of therapy [LOT]; 44.6% ISS stage I; 28.4% ISS stage III; 29.7% with extramedullary disease [EMD]; 35.7% cytogenetic high risk). No new CAR-T cell-related toxicities were reported in the analysis. ORR (87.8%), CR rate (73.0%), MRD-negative CR rate (67.6%), median DOR (23 mo), and median PFS (18 mo) were mature and the same as previously reported; median OS was previously not reached. At 65.4-mo median FU, median OS was 55.8 mo, with 33 (44.6%) pts alive and 13 (17.6%) still disease-free. Compared with pts with progressive disease (PD) or who died, pts without PD were more likely to have baseline ECOG performance status (PS) 0, IgG type MM, ISS stage I MM, numerically shorter time from diagnosis, fewer prior LOT, no light chain MM, and no EMD (Table). Conclusions: At ≥5-y FU in LEGEND-2, median OS was 55.8 mo and 18% of pts with RRMM were disease-free, raising the possibility of a cure in this heavily pretreated pt population. Our data suggest that pts who are less heavily pretreated or have good functional status may experience greater benefit, potentially being cured, from LCAR-B38M CAR-T cell therapy. Clinical trial information: NCT03090659 . [Table: see text]
Impact of bridging therapy (BT) on outcome of relapsed refractory multiple myeloma (RRMM) with Ide-cel CAR T-cell therapy: Real-world experience from the US myeloma CAR T consortium.
Authors: Afrough Aimaz , Hashmi Hamza , Hansen Doris K. , Sidana Surbhi , Ahn Chul , Dima Danai , Freeman Ciara L. , Castaneda Puglianini Omar Alexis , Kocoglu Mehmet H. , Atrash Shebli , Voorhees Peter M. , Shune Leyla , Simmons Gary , Sborov Douglas W. , Ferreri Christopher J. , Wagner Charlotte Burton , Patel Krina K. , Khouri Jack , Anderson, Jr Larry D. , Lin Yi 
Published: June 2023

8013 Background: Ide-cel is an FDA-approved treatment for RRMM patients (pts). However, there is limited data on how BT for disease control during its manufacturing process affects clinical outcomes. Methods: Eleven US academic centers contributed data to this analysis without involvement from the manufacturer. By 5/1/2022, 235 pts had undergone leukapheresis, with 214 infused with a median follow up of 9 months (mos). BT was given between leukapheresis and CAR-T infusion. Results: In this analysis, 79% of pts (n = 170) received BT, which included alkylator-based in 35.5%, steroid and/or IMiD/Ab combos (IMiD combos) in 14%, PI combinations (PI combos) in 12%, and selinexor in 10%. BT recipients had higher ECOG PS 2-4, R-ISS 2-3, ferritin, and CRP before lymphodepleting (LD) chemo, however, no difference among BT subgroups. No difference in prior lines of therapy or penta-refractory between BT and No BT (NBT) groups or BT subgroups. Median cycle of the BT was 1 (1-7), with overall response rate (ORR) of 12%, with no difference among BT subgroups. Incidence and severity of CRS and ICANs were comparable in BT and NBT. However, pts who received BT had a longer median hospital stay compared to NBT, particularly in the alkylator/selinexor subgroups. There were no significant difference in cytopenias at day 90 post CAR-T between the BT and NBT or BT subgroups. For the 73% (n = 157) evaluable for day 90 response, there was no difference in the complete or ORR between the BT and NBT groups (41% vs. 52%; p = .2 and 84% vs. 87.5%, p = .8, respectively). Median PFS was worse at 8.1 mos in BT vs 11.5 mos in NBT (p = .03). Among BT subgroups, PFS was the longest with IMiD combos with median PFS not reached (NR), comparable to NBT, and was significantly longer than all other BT subgroups (p = 0.01). The median OS was 13.8 mos with BT and NR in NBT (p = .002). In BT subgroup analysis, alkylators had a shorter OS, although, this was not significant (p = .06). There was no significant difference in PFS and OS in relationship to response to BT (p = .6 and p = .9, respectively). Conclusions: Pts without BT had longer PFS and OS post ide-cel, likely reflective of less aggressive disease. Those who received BT with steroid/IMiD and Ab combos had similar PFS as NBT. However, BT choice is complicated by disease severity and should be evaluated per patient circumstances. [Table: see text]
A phase 1 study of belantamab mafodotin in combination with standard of care in newly diagnosed multiple myeloma: An interim analysis of DREAMM-9.
Authors: Usmani Saad Zafar , Mielnik Michał , Byun Ja Min , Alonso Aránzazu Alonso , Abdallah Al-Ola A. , Garg Mamta , Quach Hang , Min Chang-Ki , Janowski Wojciech , Ocio Enrique M. , Weisel Katja , Oriol Albert , Sandhu Irwindeep , Rodríguez-Otero Paula , Ramasamy Karthik , Egger Jacqueline L. , Williams Danae , Ma Jie , Kaisermann Morrys C. , Hus Marek 
Published: June 2023

8018 Background: Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells via direct cell killing and anti-myeloma immune responses. DREAMM-9 (NCT04091126) is an ongoing Phase 1, randomized, dose and schedule evaluation study. It aims to evaluate belamaf plus bortezomib, lenalidomide, and dexamethasone (VRd) in adult patients (pts) with transplant-ineligible (TI) newly diagnosed MM (NDMM) and to establish the recommended dose for future development of belamaf combination therapies in the 1st-line setting. Herein, we report updated interim-analysis data. Methods: Belamaf dose cohorts (Co1–7) are shown in the Table. VRd was given every 3 weeks (Q3W) until cycle 8, and Rd Q4W thereafter. Following safety data from Co2–5, Co6–7 were opened in parallel (randomized 1:1) and have shorter follow-up (Table). Safety was the primary endpoint; efficacy and tolerability were secondary endpoints. Minimal residual disease (MRD) was assessed by next-generation sequencing (10-5). Results: As of data cutoff (Oct 20, 2022), 93 pts were treated across Co1–7. Median age (range) was 73 (51–88) years, 55% of pts were male, and 84% were white. The most commonly reported non-ocular adverse events (AEs) across all Co were thrombocytopenia (46%), constipation (36%), diarrhea (34%), and peripheral sensory neuropathy (31%). Overall, belamaf-related Grade ≥3 AEs occurred in 35% of pts and led to belamaf dose reductions in 7% and dose delays in 63% of all treated patients. Grade ≥3 ocular AEs (keratopathy and visual acuity [KVA] scale) occurred in 53% of all pts and led to dose reductions in 12% and dose delays in 52% of overall pts. Fatal AEs occurred in 7 pts, all unrelated to study treatment. Efficacy results and ocular AEs are summarized in the Table: 100% of pts responded in Co1 (1.9 mg/kg Q3/4W) and Co3 (1.9 mg/kg Q6/8W). Median time to very good partial response or better (≥VGPR) ranged from 2.1 to 3.1 months (mo) across cohorts. Highest MRD negativity (MRD[-]) rates (≥VGPR) were seen in Co1 (83%) and Co3 (67%). Conclusions: This updated interim analysis demonstrates that belamaf plus VRd has no new safety signals and provides early and deep anti-myeloma responses in pts with TI NDMM, with high MRD[-] rates. Clinical trial information: NCT04091126 . [Table: see text]
Busulfan, melphalan, and carfilzomib (BuMelCar) conditioning for autologous stem cell transplant (ASCT) in multiple myeloma: Phase I/II data.
Authors: Norton Joseph Allan , Hagen Patrick , Tsai Stephanie , Smith Scott E. , Lee Mary , Campo Loredana , Oldenburg David , Stiff Patrick J. 
Published: June 2023

8021 Background: Melphalan-200 high dose chemotherapy for ASCT has been the standard of care for multiple myeloma (MM) for over 30 years. Newer combination regimens such as Busulfan and Melphalan (BuMel) have demonstrated improved progression free survival (PFS) but with increased transplant related morbidity including mucositis and infections. Our group previously demonstrated that adding a proteasome inhibitor (bortezomib) to BuMel further increased PFS with mucositis ameliorated by Palifermin. Building on this effectiveness, we added carfilzomib to the BuMel backbone in a Phase I/II manner focused on safety and initial effectiveness of this novel regimen. Methods: This phase I/II open-label dose-escalation/expansion study (NCT03795597) enrolled patients with relapsed or high risk first remission MM. Patients received Busulfan over 4 days at a target total AUC of 20,000 mM-min followed by melphalan at 140mg/m2. Patients received 4 total doses of IV carfilzomib, 2 before melphalan and 2 after, with the final 2 doses escalated based on toxicity. Palifermin was given on days -11,-10, 0, and +1. Once MTD was determined, 10 more patients were treated at that level. Primary objective was safety and secondary outcomes were response to treatment at day 100 including MRD, engraftment kinetics, PFS, and OS. Results: Patients were predominantly male (79%) with median age 60.95 years. Median KPS was 80 and median HCT-CI was 2. The carfilzomib MTD was 36 mg/m2. One SAE of grade V ischemic colitis was seen at the 45 mg/m2 dose level. Toxicity at 36 mg/m2 yielded a similar pattern to our prior bortezemib containing regimen with grade 1 NSVT in 2 patients and hypertension in another. With a median follow up of 22 months, only 1 of the 13 MTD patients has progressed at 33mo. 2-year PFS and OS are both 100%. Analysis at D+100 showed 69% of MTD patients were MRD negative regardless of genetics. Conclusions: This novel BuMelCar ASCT regimen is safe and tolerable and appears to lead to a high % of MRD negative disease at D+100, which other studies correlate to a high PFS at 2 years. A comparison study with mel 200 is warranted to test whether BuMelCar can improve transplant outcomes especially in high-risk patients. Clinical trial information: NCT03795597 . [Table: see text]