bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary myeloid malignancy after CAR T cell therapy for non-Hodgkin lymphoma (NHL).
Authors: Habib Alma , Welkie Rina , Butman Jacob , Silberman Pedro C , Forero Jose Vicente , Sawalha Yazeed , Christian Beth , Maddocks Kami J. , Epperla Narendranath , Jaglowski Samantha Mary , Bond David Alan , Choe Hannah Kyung , Brammer Jonathan Edward , Kittai Adam , Bezerra Evandro , Voorhees Timothy , Vasu Sumithira , Wall Sarah Allison , De Lima Marcos J.G. , Denlinger Nathan 
Published: June 2024

7033 Background: Prior studies have described toxicities associated with chimeric antigen receptor T cell therapy (CART). Recently, myeloid malignancies were identified in myeloma patients (pt) after receipt of cilta-cel. In this study, we sought to describe the cumulative incidence and characteristics of secondary myeloid malignancies in pt treated with CART for NHL. Methods: We conducted a single institution retrospective study among pt ages ≥18 years (yr) who received commercial CART for NHL at Ohio State between December 2017 to April 2022. Descriptive statistics were used to summarize pt/disease characteristics. Cumulative incidence was calculated from date of infusion with death/relapse as competing risks. Results: For 190 pt treated with CART, median age was 63 yr (23-85 yr). Disease subtypes included diffuse large B-cell lymphoma (BCL)/high grade BCL, Richter transformation, and mantle cell lymphoma (79.5%, 8.4%, and 7.4%). Products included tisa-cel (47.9%), axi-cel (43.1%), brexu-cel (7.4%), and liso-cel (1.6%). Grade 3-4 neutropenia developed in 29% and 18% of pt at 30 days and 90 days post-CART. Median follow-up was 17 mo (0.5-63 mo). 48% were alive at time of analysis. Myeloid malignancy post-CART occurred in 7 pt with a median time to development of 29 mo (18-41 mo). Characteristics (Table) included complex karyotype, TP53 and chromosome 5/7 abnormalities. Cumulative incidence of secondary malignancy was 1%, 5%, and 6% at 2, 3, and 4 yr post-CART. Conclusions: We report on incidence of secondary myeloid malignancy in pt receiving CART for NHL. Mutational characteristics of secondary malignancies were those classically associated with therapy-related myeloid malignancy, thus presumed to be associated with prior exposure to chemotherapy (eg. alkylators/VP-16). Further investigation in larger cohorts with additional observation time, to allow for appropriate risk discussion, is required. [Table: see text]
Evaluating CR as a surrogate endpoint for PFS in R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A meta-analysis of randomized controlled trials (RCT).
Authors: Wang Lin , Disher Tim , Liu Fei Fei , Kurt Murat , Perna Serena K. , Aronitz Elise , Eyre Toby A. , Davids Matthew Steven 
Published: June 2024

7046 Background: CLL/SLL is the most common leukemia in adults. Achieving a CR by International Workshop on CLL 2018 criteria indicates complete eradication of CLL/SLL in all disease compartments. Patients with R/R CLL/SLL who achieved CR tend to have delayed disease progression/death compared with patients who did not achieve CR. This is the first report to evaluate CR as a surrogate endpoint for PFS in R/R CLL/SLL using aggregate RCT data. Methods: A systematic literature review (SLR) identified published RCTs in R/R CLL/SLL from inception to 10/2023, reporting nonzero CR rates (CRR) and PFS. Association between treatment effects on CR and PFS across RCTs was estimated using a weighted linear model (WLM) in the primary analysis, and Daniels and Hughes (D&H) and Riley bivariate random-effects meta-analysis (BRMA) in sensitivity analyses. Strength of association was assessed based on surrogacy criteria described by D&H. Predictive performance of models was evaluated using leave-one-out cross-validation. Results: The SLR identified 13 RCTs with a total of 4388 patients with R/R CLL/SLL treated with a variety of therapies, including but not limited to BTKi, BCL2i, PI3Ki, CAR T cell therapy, anti-CD20 mAb, and chemotherapy. Across the evidence base, CRR ranged from 0.48% to 38.10% and median PFS was between 1 and 35.9 months (excluding unreached medians). Across RCTs, contrasting treatment and control arms, higher odds of CR resulted in lower hazards of disease progression/death (CRR improvement translated to PFS benefit). D&H surrogacy criteria were met for WLM: 1) a near-zero, statistically nonsignificant intercept, indicating that no treatment effect on CRR implies no effect on PFS; 2) a negative, statistically significant slope, suggesting that improved CRR correlates with longer PFS; and 3) a near-zero conditional variance, meaning that PFS HR variation was primarily explained by CR odds ratio. During cross-validation, treatment effects on CR were predictive of PFS benefits, as the 95% predictive interval of PFS HR contained the observed HR in all RCTs for WLM. Results were largely consistent across all 3 models(Table). Conclusions: Improved CRR corresponds to prolonged PFS across RCTs and treatment comparisons. The results support CRR as an important treatment goal for R/R CLL/SLL and a valid surrogate endpoint. Consistent results and predictive performance across different models indicate the robustness of the results. [Table: see text]
Association between treatment (tx) response and PFS and OS in R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): A 12-month landmark (LM) meta-analysis.
Authors: Woyach Jennifer Ann , Wang Xin , Ananthakrishnan Revathi , Ou San-San , Perna Serena K. , Aptekar Jacob , Jain Rahul , Chen Weixi , Ports Kayleen , Ghia Paolo 
Published: June 2024

7047 Background: Despite advances in tx for CLL/SLL, CRs are rarely observed after tx in the R/R setting, thus impacting long-term outcomes. We evaluated the association between response after tx and survival outcomes in patients (pt) with R/R CLL/SLL. Methods: Adults with R/R CLL/SLL and ≥ 1 prior line of therapy (LOT) from 6 clinical trials (initiated after 01/01/2012 and completed before 12/31/2022) were sourced from the Medidata Enterprise Data Store. Cox models adjusted for potential prognostic factors were used to assess pt-level associations between achieving and maintaining a CR or CR with incomplete bone marrow recovery (CRi) by 12 mo after start of tx (LM date) and PFS and OS. In separate LM analyses (LMA), associations between achieving and maintaining CR/CRi, PR/nodular PR (nPR) by LM, or non-CR/non-PR (ie, those not achieving or maintaining CR/CRi or PR/nPR or not evaluated by LM), and PFS and OS were assessed. Results: Of 1604 pts (CLL, 97.7%; SLL, 2.3%; age ≥ 65 y, 61.8%; male, 66.6%; ECOG PS 0–1/2, 93.2%/6.8%; median [IQR] follow-up, 3.4 y [2.2–4.1]; median [IQR] LOT, 2 [1–3]; study tx, BTKi [40.4%], BCL2i [40.1%], anti-CD20 mAb [12.5%], and PI3Ki [9.9%]), 15.1% and 61.7% achieved a best overall response of CR/CRi and PR/nPR, respectively (ORR, 76.8%); 6.8% of pts had no response recorded in follow-up. A total of 1178 pts without progression, death, or censoring before LM were included in PFS LMA. Median (95% CI) PFS from LM was 64.4 mo (61.7–not reached [NR]) for CR/CRi, 43.3 mo (38.8–54.7) for PR/nPR, and 23.9 mo (18.3–50.6) for non-CR/non-PR. Pts who achieved and maintained CR/CRi had significantly longer PFS versus both non-CR/CRi and PR/nPR pts, with adjusted HR of 0.62 ( P = 0.01) and 0.64 ( P = 0.02), respectively (Table). For OS LMA, 1404 pts without death or censoring before LM were included. Median (95% CI) OS from LM was NR for CR/CRi and PR/nPR groups and 62.9 mo (51.2–NR) for non-CR/non-PR. At 24 mo from LM, 90% (85%–95%) CR/CRi, 87% (84%–89%) PR/nPR, and 72% (67%–77%) non-CR/non-PR pts were still alive. CR/CRi pts or PR/nPR pts had significantly longer PFS and OS versus non-CR/non-PR pts. Conclusions: We demonstrated that achieving and maintaining CR/CRi by 12 mo after start of tx was associated with significantly improved PFS versus achieving and maintaining PR/nPR, which was also better than not achieving/maintaining any response. These findings support the potential utility of durable CR/CRi as an informative early endpoint for assessing the value of tx in pts with R/R CLL/SLL. Adjusted HR (95% CI) [Table: see text]
Non-Hodgkin lymphoma mortality disparities across different sexes, races, and geographic locations.
Authors: Tan Jia Yi , Yeo Yong Hao , Patel Aharnish , Chan Kok Hoe , Chisti Mohammad Muhsin , Ezekwudo Daniel 
Published: June 2024

7063 Background: Non-Hodgkin lymphoma (NHL) is one of the common hematological cancers in the United States (U.S.), accounting for 4% of new cancer cases in 2023. The mortality rate of NHL is the sixth highest among all cancers in the U.S. Our study aimed to examine the trends in NHL mortality and assess the mortality disparities among different sexes, ages, races, geographic locations, and urbanization levels. Methods: Our population-based cross-sectional study analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) U.S. from 1999 to 2020 to determine the longitudinal trends of NHL mortality among the U.S. population aged ≥ 15 years. NHL (ICD-10 C82-85) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated and joinpoint trend analysis were performed to determine the average annual percent change (AAPC) in AAMR trends. Results: From 1999 to 2020, NHL accounted for 457,143 deaths in the United States, of which 54% are men and 46% are women. Excluding unspecified NHL, there were 132,288 (n=132,288/155,957, 84.8%) B cell NHL deaths and 23,669 (n=23,669/155,957, 15.2%) T cell NHL deaths. Overall, the AAMR of NHL decreased from 10.59 (95% CI, 10.46-10.73) in 1999 to 6.21 (95% CI,6.13-6.30) in 2020 with the AAPC of -2.55 (95% CI, -2.63, -2.46). Men had a higher AAMR than women (10.10 [95% CI, 10.06-10.14] vs. 6.29 [95% CI, 6.27-6.32]). Non-Hispanic Whites recorded the highest AAMR (8.43 [95% CI, 8.40-8.45]), followed by non-Hispanic Blacks (5.71 [95% CI, 5.64-5.77]), Hispanics (6.32 [95% CI, 6.25 - 6.40]), American Indians (5.31 [95% CI, 5.04 - 5.58]), and Asians (5.10 [95% CI, 5.00 - 5.19]). Death from NHL was the most common in patients aged 75 years and above (52.50%), followed by patients aged 55-74 years (37.49%) and patients aged 15-54 years (10.41%). Those who lived in the Midwest region had the highest AAMR (8.60 [95% CI, 8.55-8.65], followed by the Northeast region (7.99 [95% CI, 7.94 - 8.05]), the South region (7.73 [95% CI, 7.70 - 7.77]), and the West region (7.58 [95% CI, 7.54 - 7.63]) . The rural population has a higher AAMR compared to the urban population (8.35 [95% CI, 8.29-8.41] vs. 7.86 [95% CI, 7.83 - 7.88]). Conclusions: NHL mortality has declined over the last two decades. The higher mortality rates existed among men, non-Hispanic White individuals, and the rural population warrant targeted intervention to address the mortality disparities.
Clinical and financial burden of mental health (MH) conditions in patients (pts) with low-grade non-Hodgkin lymphoma (LG-NHL).
Authors: Yang Keri , Esselman Kaitlyn , Chuang Po-Ya , Furnback Wesley , Chanan-Khan Asher Alban Akmal 
Published: June 2024

7072 Background: LG-NHL is mostly incurable, imposing a prolong impact of cancer care burden for pts. This study aimed to quantify the burden of MH conditions in pts with newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), or marginal cell lymphoma (MZL). Methods: A retrospective study was conducted using Optum Clinformatics Data Mart to identify pts ≥18 years with ≥1 new diagnosis for CLL, FL, MCL, WM, or MZL from 6/2016-6/2022 (index period). Pts were required to be continuously enrolled for 60 days pre- and 365 days post-index date, defined as the date of first cancer diagnosis. Incidence and prevalence of MH conditions of interest (anxiety, depression, stress reaction/adjustment disorder, insomnia, post-traumatic stress disorder [PTSD]) were categorized based on if diagnoses were post- or pre-index date. All-cause healthcare resource utilization (HCRU) and costs were measured during the 1-yr follow-up period. Results: Approximately half of newly diagnosed 36,054 LG-NHL pts (CLL/SLL=48.0%; FL=52.7%; MCL=57.2%; WM=50.5%; MZL=52.5%) had either an incident (19.4-25.7%) or prevalent (28.6-32.1%) MH condition diagnosis following their cancer diagnosis (Table). There were no significant demographic differences in pts with and without MH conditions. LG-NHL pts suffered most from anxiety (30.9-38.2%) and depression (27.5-31.9%), followed by insomnia (16-23.1%), stress (10.3-13.5%), and PTSD (1.4-1.9%). Median time from cancer diagnosis to onset of a MH condition was 334 days for CLL/SLL, 301 for FL, 248 for MCL, 351 for WM, and 328 for MZL. LG-NHL pts with an identifiable MH diagnosis had significantly higher costs and HCRU compared to those without; for example, in CLL/SLL pts with MH diagnosis, outpatient visits were 1.4 times higher, inpatient admissions 3.0 times higher, and costs 2.1 times higher than those without (all P=0.0001). HCRU and cost increases were also observed in MCL, FL, WM, and MZL pts with MH diagnosis. Conclusions: This real-world study uncovered a high proportion of LG-NHL patients suffer from MH conditions, incurring higher financial burden than those without. With advancements in new treatments, there remains unmet need of MH burden in these pts. [Table: see text]
Survival outcomes after autologous stem cell transplantation in T follicular helper type lymphoma.
Authors: Lionel Anath Christopher , Elias Alexandra , Prakash Rishab , Vega Francisco , Patel Keyur P. , Hosing Chitra M. , Malpica Luis , Nair Ranjit , Srour Samer Ali , Iyer Swaminathan Padmanabhan 
Published: June 2024

7073 Background: T follicular helper (TfH)-type lymphoma is the most common subtype of peripheral T-cell lymphoma (PTCL). TfH lymphoma consists of angioimmunoblastic T-cell lymphoma (AITL), PTCL-TfH and Follicular T cell lymphoma. Most patients receive first-line treatment with anthracycline-based chemotherapy regimens with a potential role for consolidation with autologous stem cell transplantation (ASCT). In this study we analyzed survival outcomes in TfH lymphoma. Methods: This is an IRB approved retrospective analysis of patients with TfH lymphoma followed between 1997–2023 at the MD Anderson Cancer Center. Demographics, treatment history, response and survival outcomes were collected and analyzed. Next-generation sequencing (NGS) data was collected from a panel of 162 cancer-related genes. Survival analysis was performed with Kaplan Meier curves and comparisons were made with log-rank tests. Results: Of the 218 patients with TfH lymphoma for whom information was known about prior history of ASCT, 84 (39%) underwent ASCT (Table). At the time of diagnosis, the majority of patients had advanced stage disease (92% with stage III or IV) and elevated LDH (89%). NGS testing was available from 31 patients and the genes with recurrent somatic mutations identified were TET2 (65% patients), DNMT3A (29%), RHOA (13%), IDH2 (10%), PLCG1 (10%), TP53 (10%), ATM (6%), CCR7 (6%), JAK3 (6%) and STAT3 (6%). The three most common first-line treatments were CHOP (37%) followed by CHOEP (14%) and combination of brentuximab with either CHP or CHEP (13%). Patients who received ASCT were significantly younger (Table). The median overall survival (OS) for the cohort was 40.3 months with median progression-free survival (PFS) after first treatment of 12.5 months. Patients who received ASCT had a significantly higher overall survival (log-rank test p-value < 0.01) compared to those who did not receive ASCT. Conclusions: This retrospective analysis of a large single institution cohort of patients with TfH lymphoma found significantly improved OS in those who underwent ASCT compared to those who did not. Given the sizeable proportion of patients who are transplant-ineligible due to age or comorbidities, there is a need for newer consolidation approaches for TfH lymphoma. [Table: see text]
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: Cerchione Claudio , Nappi Davide , Marchesini Matteo , Cangini Delia , Ronconi Sonia , Ceccolini Michela , Prochowski Iamurri Andrea , Matteucci Federica , Simonetti Giorgia , Musuraca Gerardo , Martinelli Giovanni , Rossi Alice 
Published: June 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.
Expression of alternatively spliced BCMA RNA with skipping of transmembrane domain.
Authors: Ip Andrew , Albitar Maher , Zhang Hong , Charifa Ahmad , Agersborg Sally , Mohtashamian Arash , Siegel David Samuel DiCapua , Biran Noa , Vesole David H. , Pecora Andrew L , Goy Andre 
Published: June 2024

7514 Background: The TNFRSF17 gene, which encodes for the B cell maturation antigen (BCMA), is a small gene expressed mainly on the surface of plasma cells and some DLBCL cells. This gene is composed of three exons. Exon 1 is responsible for the extracellular domain, exon 2 for the transmembrane domain, and exon 3 for the TRAF binding domain. The BCMA is currently targeted by various types of immunotherapies as a major therapeutic approach for the treatment of multiple myeloma (MM). This includes CAR-T cells, bi-specific antibodies, and antibody-drug conjugates (ADC). However, emerging data indicates that alternative splicing in genes is an important mechanism for expression of different isoforms that may influence antibody-based therapies. We explored the potential of the presence of alternative splicing in BCMA transcripts via sequencing of BCMA RNA in patients with lymphoma or multiple myeloma. Methods: RNA was extracted from 587 fresh bone marrow samples with lymphoid/plasma cell neoplasms or from FFPE samples with lymphoma. In addition, cfRNA was extracted from 260 peripheral blood plasma samples from patients with lymphoma or multiple myeloma. RNA was sequenced using a hybrid capture-targeted RNA panel with analysis focused on TNFRSF17 (BCMA) gene transcript. Quantification of RNA transcript was done using Salmon algorithm. Results: Of the 587 lymphoma/plasma cell samples, 161 (27%) samples showed alternative splicing involving deletion of exon 2 (BCMA∆Ex2). Of the 260 cfRNA samples, 14 (6%) showed BCMA∆Ex2. The median percentage of BCMA∆Ex2 transcripts was 0.7% of total BCMA transcripts in cellular samples as compared with 9% in cfRNA samples. In cellular samples, there was a correlation between levels of BCMA and BCMA∆Ex2 (R=0.63). Cases with higher levels of BCMA had significantly higher levels of BCMA∆Ex2 (P<0.0001, Kruskal-Wallis). In contrast, cfRNA showed no correlation between levels of BCMA and levels of BCMA∆Ex2 (R=021, Spearman) and mildly higher level of BCMA∆Ex2 in cases with higher levels of BCMA (P=0.002, Kruskal-Wallis). Conclusions: BCMA exon 2 skipping is detected in a significant number of patients with multiple myeloma and lymphoma. The percentage of skipping transcripts is low in cells and relatively higher in cfRNA. Since exon 2 skipping deletes the transmembrane domain, this BCMA protein may remain in the cytoplasm or perhaps is secreted as cell-free BCMA protein. The demonstration of relatively higher levels of BCMA∆Ex2 in cfRNA is likely reflecting higher turnover of cells and raises the possibility that cells with this isoform of BCMA are more aggressive than cells without the expression of this isoform. Further studies are needed to explore the clinical relevance of the expression of such abnormal BCMA protein on treatment with the various forms of anti-body-based therapy or CAR-T.