bluuebunny/crossref_metadata_2025 huggingface dataset:
In-hospital outcomes of patients with myelodysplastic syndromes and rheumatic heart disease: A National Inpatient Sample study (2018-2020).
Authors: Iqbal Rabia , Gaddam Mrunanjali , Bajwa Ahmad Taimoor , Colon Ramos Ana , Sinha Samridhi , Singh Surbhi , Singh Surbhi , Clement Jincy
Published: June 2024

e18525

Background: Autoimmune conditions are relatively uncommon in patients with Myelodysplastic syndromes (MDS), with only a small proportion of patients affected. Among these autoimmune conditions, rheumatic heart disease (RHD) is the most commonly associated with MDS. Very few cases have been reported in literature that show the impact of RHD on patients diagnosed with MDS. In this study, we aimed to investigate the impact of RHD on the patients with myelodysplastic syndrome who were admitted in hospitals from 2018-2020. Methods: We utilized National Inpatient Sample (NIS) 2018-2020 to identify hospitalizations of patients with Myelodysplastic syndromes with a secondary diagnosis of Rheumatic heart disease. The primary outcomes examined were In-patient mortality and average length of stay, All the patients with MDS were divided into two cohorts based on the presence of rheumatic heart disease. Multivariable regression analyses were conducted, taking into account demographics, hospital-level characteristics, and pertinent comorbidities as adjusting factors. Results: Using the NIS dataset from 2018 to 2020, we identified 222,364 patients admitted with MDS during this period. Among them, 4.57% (10,162 patients) also had a diagnosis of rheumatic heart disease (RHD). The average age of patients with MDS and RHD was 80 years. Among these patients, 50.1% were male and 49.9% were female. The mortality rate among patients admitted with MDS and coexisting RHD was 7.7%. Multivariate regression analysis indicated that the presence of RHD increased the likelihood of mortality with an odds ratio (OR) of 1.2 (95% confidence interval [CI]: 1.0-1.4, p-value <0.05). Additionally, RHD was associated with a higher incidence of arrhythmias (OR: 2.9) and congestive heart failure (OR: 5.0) among MDS patients. The total hospital charges were more in patients with RHD than those without RHD ($80108 vs $82843). However, there was no significant difference in the length of stay (LOS) between patients with MDS alone and those with MDS and RHD. Conclusions: Rheumatic heart disease (RHD) cases in patients with MDS are rare in clinical practice, leading to uncertainty regarding the effects of RHD on admitted MDS patients. Our study sheds light on the influence of RHD on mortality and other outcomes in this patient population. The efficacy of timely RHD treatment in reducing mortality and improving outcomes among hospitalized MDS patients remains to be verified in future investigations. [Table: see text]
Analyzing the characteristics and prognostic outcomes for patients with myelodysplastic syndrome with Q-gene deletion.
Authors: Nnawuba Kingsley Chinonyerem , Lockwood Matthew Blake , Nzeako Tochukwu , Guyo Zeytun , Al Fazal Mohammad , Jensen Hanna
Published: June 2024

e18526

Background: Myelodysplastic syndromes (MDS) are a group of hemopoietic disorders in which the bone marrow is deficient in producing healthy mature blood cells. MDS associated with a deletion in the long arm of chromosome 5Q is a rare occurrence, but considered a good prognosis in comparison to other subgroups of MDS. There has been limited focus directed towards this variant of the disease, especially concerning outcomes among different demographics. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End-Result (SEER) registry research database 17 (2000 -2020) was used to assess & compare the outcomes for this variant of MDS in adult & AYA pts. Univariate & multivariate analyses was performed and cox proportional hazards regression was used to assess prognostic outcomes. A two-sided pvalue ≤0.05 was considered significant. Results: Analysing (table) 2,323 pts identified, 98.92% (n= 2298) were adults ≥40yrs, and 1.08% (n= 25) were AYAs. AYAs comprised 32% Hispanic, 4% Non-Hispanic Asian or Pacific Islander (NHAPI), 16% Non-Hispanic Black (NHB), and 48% Non-Hispanic White (NHW). Compared to adults, AYAs had higher proportions of Hispanics and NHBs but fewer NHWs. AYAs showed longer average survival (57.7 vs 33 months) than older adults. Females generally had longer survival periods than males in both AYA (64.4 vs 49.1 months) & adult (37.2 vs 26.4 months) groups. Among adult racial groups, Non-Hispanic Black females had the poorest prognosis (29.6 months), while Hispanic males had the worst prognosis overall (21 months). Among AYAs, Hispanic females had the worst prognosis (4 months), followed by Hispanic males (24.2 months). Conclusions: Our study shows AYAs are less likely to die from MDS compared to adults ≥40. Hispanic females appear to have a worse outcome than males in both age groups & is independent of other analysed prognostic factors. More research is needed to examine other prognostic factors with the aim of improving survival outcomes. [Table: see text]
Patient reported outcomes among U.S. Veterans living with myeloproliferative neoplasms.
Authors: Mathur Natasha , Tiu Andrew Chua , Brazeau Ann , Giocondo Natalie , Gill Puneet , Liu Shanshan , Diao Guoqing , Subrahmanyam Ramesh , Kessler Craig M , Jain Maneesh Rajiv
Published: June 2024

e18528

Background: Myeloproliferative Neoplasms (MPNs) profoundly affect patients' well-being, necessitating effective symptom relief. Patient-reported outcomes are pivotal for care improvement, aligning with Centers for Medicare and Medicaid Services priorities. This study aims to assess MPN symptom burden among U.S. Veterans, examining risk levels, thrombo-hemorrhagic complications, medication use, information access, care, and service-connected benefits. Methods: Conducted as a cross-sectional survey from December 1, 2023, - January 22, 2024, all Veterans in the MPN Advocacy Education & International database were recruited. Symptom burden was assessed using the validated MPN Symptom Assessment Form Total Symptom Score (MPN SAF TSS), with descriptive statistics and T-tests employed for analysis. Results: Of 61 respondents, 88% were male, 92% Caucasian, 88% served during the Vietnam war. The mean age was 73±7, with MPN diagnosis at 64±9 and a mean duration of 44±10 years from service-connected exposure. Key findings included 56% Polycythemia Vera, 26% Essential Thrombocythemia, 16% Primary Myelofibrosis, 70% JAK2, 10% CALR, 3% MPL, 14% unaware of their mutation status, and 34% unaware of MPN risk status. Seventeen (28%) underwent phlebotomy, 64% used Hydroxyurea, 29% Ruxolitinib, and 3% Interferon. Fatigue and itching were the predominant and severe symptoms (Table), with 43% reporting no symptom improvement. Mean MPN SAF TSS of all respondents was higher than prior study by Emanuel et.al. which adjusted for MPN subtype (36.4 vs. 21.6, p<0.0001). Twelve (20%) reported bleeding and 10% reported venous thrombosis after MPN diagnosis, while 13% reported arterial thrombosis before MPN diagnosis. Twenty-two (36%) are not seeing an MPN specialist and 61% are not seeing a hematologist at their local Veterans Affairs Medical Centers. Twenty-three (38%) did not seek a second opinion while 43% do not have a caregiver. Respondents turn to MPN organizations (75%), physician offices (74%), Google Search (49%), Webinars (41%), and Facebook (23%) for information. Five (8%) received service-connected disability benefits. Conclusions: Veterans with MPNs endure a substantial symptom burden, surpassing previous studies, signifying suboptimal management. Limited access to care persists, necessitating enhanced support. However, self-reporting bias and potential limitations in activity assessment must be acknowledged. Efforts to enhance MPN awareness, specialized care, and support mechanisms are imperative for comprehensive management. [Table: see text]
A call for improved anemia treatments in myelofibrosis: A single-center retrospective study.
Authors: Yan John , Kamel Josette Mary , Goel Swati , Verma Amit
Published: June 2024

e18531

Background: Anemia in myelofibrosis (MF) is associated with poor prognosis and decreased quality of life. Effective treatments are limited, posing a significant challenge in clinical management. This study aims to provide insights into the treatment of anemia in MF patients from an underserved urban tertiary care center. Methods: We retrospectively reviewed 88 MF patients referred to our center in the Bronx, NY between 2000 and 2023. Demographic data, presence of anemia (hemoglobin ≦10 g/dl) at time of diagnosis or referral (TODR), transfusion dependence ( ≥ 2 units on ≥2 occasions within 8 weeks), anemia treatments, disease modifying treatment, and anemia response to treatments (as defined by the IWG-MRT and ELN consensus report) were assessed via non-parametric tests and univariate cox regression. Events were defined as death from any cause or development of anemia. Patients with missing data were excluded. Results: Among 88 patients analyzed, 77 (87.5%) experienced anemia during the study period. Overall survival (OS) for anemic patients was 7.7 years with 31 deaths, versus only 1 death in the non-anemic group. 51 (60%) of patients were anemic at TODR. For patients not anemic at TODR, median time to anemia (TTA) was 31 months. Patients with HMR (n=24) had faster median TTA than those without (22 vs. 49 months, p = 0.1). All triple-negative (TN) patients (n=8) were anemic at TODR and had statistically lower initial hemoglobin compared to patients with driver mutations (7.4 g/dl vs. 9.9 g/dl, p = 0.0023). Among anemic patients (n=77), age > 65 was associated with poorer OS (HR 2.293, CI 1.076 - 4.887, p=.0315), while transfusion dependency (HR 2.093, CI 0.4777 - 0.9422, p=0.0697) and Ruxolitinib use (HR 2.843, CI 0.9912 - 8.155, HR 0.052) approached significance. Secondary anemia treatments did not impact OS (HR 0.9346, CI 0.4537 - 1.925, p=.854) and are summarized in the table. Most patients received Ruxolitinib (68.8%) and hydroxyurea (35.06%), while fewer received Momelotinib (N = 4), Pacritinib (N = 6), or Fedratinib (N = 4). Conclusions: Our findings highlight the limited effectiveness of current treatments in reducing transfusion burden and anemia in MF, and that patients of higher genetic risk may be more susceptible to developing anemia. Transfusion dependency and treatment non-response are marginally associated with poorer outcomes, emphasizing the need for newer therapies. [Table: see text]
Safety and feasibility of outpatient CAR-T therapy: A single center analysis.
Authors: Soror Noha , Davis Olivia , Diaz Adolfo , Day Silas , Machiorlatti Michael , Pandey Manu , Ibrahimi Sami , Khawandanah Mohamad Osama , Holter Jennifer , Asch Adam Steven , Al-Juhaishi Taha
Published: June 2024

e19005

Background: Chimeric Antigen Receptor modified R Cell Immunotherapy (CAR-T) cell products have revolutionized the landscape of treatment of relapsed and refractory (R/R) B-cell malignancies and multiple myeloma. Yet, these therapies emerged with their own challenges, Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common and serious adverse events. The model of CAR-T cell therapy in the University of Oklahoma is unique as it is designated as an outpatient therapy. Little is known regarding risk factors for hospitalization after CAR-T therapy. Methods: This is a retrospective analysis of all consecutive adult patients who had CAR-T therapy from 9/1/2019 through 9/30/2023 at the University of Oklahoma Health Sciences Center (OUHSC). Inclusion criteria were adult patients with hematologic malignancies who received an FDA approved CAR-T therapy. Exclusion criteria included patients who were younger than 18 at the time of infusion, those who received cellular therapy for solid tumors and those who received investigational CAR-T cell products. Descriptive statistics were created for continuous and categorical variables. Chi-Square analysis and independent samples t-tests were used to measure association with hospital admission and treatment response. Logistic regression was used to explore associations for all covariates with each outcome. SAS 9.4 was used to perform all analysis. An alpha of 0.05 was used to determine significance. Results: A total of 118 patients received outpatient CAR-T/Cellular therapy at OUHSC during the study period with 78 patients meeting the inclusion criteria. The mean age at time of infusion was 58.6 (range=18-85) with most being male (n=46, 59.0%), White (n=63, 80.8%), and overweight/obese (n=50, 64.1%). The majority of patients received anti CD19 CAR-T (n=64, 82.1%) while 18.0% received anti BCMA products. CRS grade 0,1 occurred in 79.5% of patients (n=62) and 79.2% of patients were hospitalized within 30 days after CAR-T therapy (Median day of admission post CAR-T=5.5). Of patients who were hospitalized 26% had grades 2-4 CRS. Complete remission was achieved in 54.7% of patients. We compared the hospitalized and non-hospitalized patients across multiple characteristics, there was no association or predictors of hospitalization found. Albumin was the only predictor for CR. Conclusions: Our study provides data for safety and feasibility of outpatient CAR-T therapy despite potential risks for hospitalization. There are no clear predictors for hospitalizations after CAR-T therapy except for the development of CRS and ICAN. Higher baseline (pre-CAR-T) serum Albumin level was associated with higher odds of achieving CR.
Prevalence of adverse events following bispecific antibody therapy in non-Hodgkin lymphoma: A meta-analysis.
Authors: Liu Alex John , Fonseca Rodrigo , Langlais Blake , Almader-Douglas Diana , Hilal Talal
Published: June 2024

e19008

Background: Bispecific antibodies (BsAb) have emerged as a new treatment modality for relapsed/refractory non-Hodgkin lymphomas (R/R NHL). They exert their effect by binding to CD3 on T-cells and CD19 or CD20 on lymphoma cells, activating the T-cell to exert cytotoxic effects against the tumor and normal B-cells. Treatment related adverse events (TRAE) include infections, cytokine release syndrome (CRS), neurotoxicity (ICANS). This meta-analysis was conducted to assess prevalence of TRAEs from prospective clinical trials that evaluated BsAb in R/R NHL. Methods: A systematic review was conducted through PubMed, Embase, Scopus, Web of Science, and Cochrane to identify BsAb clinical trials in NHL through October 2023. Eligible studies included phase I-III trials evaluating BsAb in any type of NHL, either as monotherapy or combination therapy irrespective of prior lines of treatment. Primary outcomes of interest include infection, neutropenia, CRS, and ICANS. All studies were weighted equally. Pooled prevalence estimates of TRAE were calculated using common and random effects models. Heterogeneity tests were performed using Cochran’s Q test. Subgroup analysis examined infection rates in monotherapy versus combination therapy cohorts. Results: After screening 1039 studies, 36 clinical trials with 2162 patients were included. The lymphoma subtypes were diffuse-large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. The BsAbs included mosunetuzumab (13 studies), epcoritamab (10 studies), blinatumomab (5 studies), glofitamab (5 studies), odronextamab (2 studies), and AFM11 (1 study). The median age of patients was 66 years, and patients had received a median of two prior lines of therapy. Median follow-up duration was 9.1 months. The prevalence of all-grade infections was 35% (95% CI: 0.33-0.38; I2 = 79%). For grade ≥3 infections, the prevalence was 16% (95% CI: 0.14-0.18, (I2 = 77%). There were higher rates of all-grade infections in the combination therapy cohort (41%, 95% CI: 0.36-0.47) compared with the monotherapy cohort (33%, 95% CI: 0.30-0.36). All-grade and grade ≥3 neutropenia occurred in 31% (95% CI: 0.29-0.34; I2 = 80%) and 22% (95% CI: 0.20-0.24, I2 = 61%) of patients. CRS was observed in 45% of patients (95% CI: 0.43-0.48, I2 = 85%). Grade ≥3 CRS occurred in only 2% of patients (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). ICANS occurred in 12% (95% CI: 0.10-0.14, I2 = 90%) while grade ≥3 ICANS was rare, at 3% (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). Conclusions: BsAb is associated with nontrivial rates of infections and neutropenia. The rates of high grade CRS and ICANS are low. The heterogeneity of the findings could be attributed by an underreporting of TRAE and small sample sizes from various studies. These results highlight the need for vigilant practices to diagnose and treat infections early and consideration for antibacterial prophylaxis in this immunocompromised population.
Bridging therapies used in trials testing CAR-T therapies.
Authors: Prasad Vinay , Kaestner Victoria , Haslam Alyson
Published: June 2024

e19011

Background: Chimeric Antigen Receptor T-cell (CAR-T) therapy can induce durable remission in some patients but requires time for a patient’s own cells to be reengineered to produce CAR proteins that can bind to and destroy cancer cells. During this time, bridging therapy is often used in debulking to reduce treatment toxicities and to control the disease while waiting for the manufacturing of CAR-T cells. Because bridging therapy often involves systemic treatment, the bridging therapies can induce responses, in and of themselves, in clinical trials testing CAR-T therapies. As such, we sought to assess bridging therapies used in CAR-T trials. Methods: Using the FDA labels (labels.fda.gov) to identify the indications and the pivotal clinical trials that led to the approval of each CAR-T cell therapy, we looked at which bridging therapies were used, whether multiple therapies were combined, response rates, and the reported adverse events associated with bridging therapy. We took note of all relevant comments regarding bridging therapy in the main paper and supplemental results. Results: Of the 11 studies testing CAR-T therapies, 10 reported the bridging therapies that were used in the study. Notably, only three of 11 studies provided clear information about which combinations of bridging therapy treatments were used during the trials. Of those that reported the types of bridging therapies (n=10), the most commonly used bridging therapy was dexamethasone, which was used in every study (10/10). The next three most commonly used treatments include rituximab (6/10), gemcitabine (5/10), and etoposide (5/10). Of the trials, 2/11 clearly reported whether patients had a complete response (CR), partial response (PR), or very good partial response (VGPR) to bridging therapy. 5/11 vaguely reported responses, using terminology outside of CR, PR, VGPR. 4/11 trials did not report or mention any response information in regards to bridging therapy. Of all the trials, 1/11 clearly reported adverse events associated with bridging therapy in the supplement, while 10/11 of the trials listed adverse events associated with the treatment groups, without clarifying those associated with bridging. Conclusions: Although patients are often refractory to first-line therapies, which share considerable overlap with the bridging therapies used, these therapies may still induce responses. Despite this possibility, the reporting of bridging therapy combinations and their subsequent response rates and adverse event rates, is highly variable. Of 11 pivotal clinical trials that led to the approval of a CAR-T cell therapy, none clearly reported bridging therapy data that encompassed all three categories (combinations used, response rates, adverse events). What is more, these data were often omitted completely. These findings highlight the need for greater transparency in the reporting of bridging therapy in order to more reliably assess the efficacy of CAR-T therapies.
Evolving patterns of transplant strategies for mantle cell lymphoma in the era of BTK inhibitors and CAR-T therapy.
Authors: Maddukuri Ashok , Inoue Yoshitaka , Rakszawski Kevin , Claxton David , Ehmann Christopher , Zheng Hong , Minagawa Kentaro , Mineishi Shin , Naik Seema
Published: June 2024

e19012

Background: Mantle cell lymphoma is an aggressive lymphoma with poor survival after chemotherapy alone. Both autologous (auto) and allogeneic (allo) transplants have improved outcomes over the years, but transplant strategies most beneficial for MCL are not clearly defined. Recently, BTK inhibitors and chimeric antigen therapies (CAR T) therapy approach has changed the landscape of Mantle cell Lymphoma. Methods: Patient Population:A total of 71 patients underwent transplant for diagnosis of MCL at Penn State Cancer Institute, between March 1993 and March 2023. Median follow up was 3.1 years (32 days-9883 days) after transplant. Patient Characteristics: A total of 71 patients (62 M: 9 F) underwent transplants, including autologous (n=30), allogeneic (n=32), and CAR T (n=9). Since 2020, 19 transplants were performed: CAR T (n=9) auto transplants (n=9) and allogeneic transplants (n=1). Relapsed and refractory MCL (n=4) patients received CAR T whereas patients achieving CR 1 (n=8) and PR1 (n=1) received auto transplants. Most patients were Caucasian (n= 68), with few Hispanic (1), African American (1), or Asian (1). Results: Median age at the time of transplant was 61 (37-70) years for autologous, 56 (33-67) years for allogenic and 63 (55 -75) years for CAR T respectively. Disease status at transplant was CR 52.1% (n=37), primary induction failure or relapsed/refractory 36.6% (n=26), PR 11.3% (n=8). High LDH was seen at the time of transplant in 16.9% (n=12) patients and normal in 83.1%(n=59) patients. Blastoid morphology was seen in only 13.8% (n=4) autologous, 37.9% (n=11) allogenic and 33.3% (n=3) CAR T patients. Outcomes: Overall survival (OS) at 1 year and 3 years was 93.3% and 85.9% for autologous (auto) transplants, 62.5% and 52.9% for Allogeneic (allo) transplants, 88.9% and 76.2% for CAR-T therapy respectively (P = 0.007). Progression free survival at 1 year and 3 years was 86.3% and 75.0% for auto transplants; 50.0% and 43.3% for allo Transplants; 66.7% and 66.7% for CART Therapy (P = 0.03). Primary cause of death was Treatment Related Mortality (TRM) (n= 9) (GVHD=4; Pulmonary=3; MOF=2) and disease progression (n=10); unknown (n=4); other (n=1). Primary cause of death for CAR T therapy was grade IV ICANS and disease progression. Conclusions: Recently CAR T therapies have changed the landscape of MCL treatment algorithm in both Blastoid and non-Blastoid histology MCL patients. But in the era of CAR T therapy and BTK inhibitors for MCL, achieving CR at the time of transplant predicts improved long-term outcomes. Randomized studies or larger retrospective CIBMTR data analysis may be important to answer best transplant strategy for MCL patients. [Table: see text]
Risk of hypertension in patients with CLL/SLL who participated in ALPINE: A post hoc analysis.
Authors: Ramirez Dulce , Chen Lipeng , Zhang Jun , Aldairy Wassim , White William B.
Published: June 2024

e19016

Background: Bruton tyrosine kinase (BTK) inhibitors are an important therapeutic option for patients with CLL/SLL. The first-generation BTK inhibitor, ibrutinib (ibru), is associated with an increased risk of hypertension. Zanubrutinib (zanu) is a next-generation BTK inhibitor designed to maximize BTK occupancy and minimize toxicity with fewer off-target effects. This analysis evaluated the risk of developing hypertension based on initiation of antihypertensives (anti-HTN) in ALPINE (NCT03734016). Methods: Anti-HTN use in the zanu (n=324) and ibru (n=324) treatment arms was assessed. The definition of anti-HTN was based on Standardized Drug Grouping; concomitant anti-HTN were adjudicated by an independent hypertension specialist blinded to BTK inhibitor assignment. Time to initiating new anti-HTN and time to adding a new class of anti-HTN were assessed using the Kaplan-Meier method. Comparisons of time-to-onset endpoints were analyzed based on the log-rank test. Results: At baseline, patient characteristics were generally balanced between zanu and ibru arms (median age, 66.7 vs 67.1 y; male, 65.1% vs 71.4%; history of hypertension, 50.9% vs 50.0%; type 2 diabetes mellitus, 10.1% vs 8.9%). Among patients not on anti-HTN at baseline, 20.7% (n=35/169) of zanu- and 28.7% (n=51/178) of ibru-treated patients initiated anti-HTN during the study. Among all patients, fewer patients in the zanu arm initiated new anti-HTN (28.4% [n=92/324] vs 32.4% [n=105/324]) and the anti-HTN were initiated later (hazard ratio [HR], 0.77; P-value=.071). Additionally, statistically fewer patients in the zanu arm compared with the ibru arm started anti-HTN in a new class (24.1% [n=78/324] vs 29.3% [n=95/324]) and the anti-HTN were started later (HR, 0.72; P-value=.034). The event rates for initiation of new anti-HTN or a new class of anti-HTN were consistently lower in the zanu vs ibru arm at each timepoint (Table). Conclusions: In ALPINE, initiation of new anti-HTN or a new class of anti-HTN occurred less frequently in the zanu arm vs the ibru arm in patients with CLL/SLL. Adoption of anti-HTN occurred sooner with ibru than zanu. These findings should be considered when initiating BTK inhibitor therapy in patients with CLL/SLL who have an elevated cardiovascular risk. Clinical trial information: NCT03734016 . [Table: see text]
Real-world outcomes following adverse events and dose reduction of first-line ibrutinib in Medicare beneficiaries with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Authors: Shadman Mazyar , Srivastava Bhavini P. , Salkar Monika , Saifan Chadi , Agatep Barnabie C. , Jones Barton , Ryan Olga , Bacchus Shaffee , Stephens Deborah M.
Published: June 2024

e19017

Background: Dose reduction (DR) has been used to manage treatment-related adverse events (AEs) effectively and avoid early treatment discontinuation in patients (pts) with CLL/SLL receiving ibrutinib (ibr) in the first-line (1L) setting. This study evaluated DR and time to next treatment (TTNT) following AE in Medicare pts with CLL/SLL who were initiating ibr. Methods: Medicare Fee-for-Service (FFS) closed claims and enrollment data were used to identify pts with CLL/SLL who initiated 1L single-agent ibr (420 mg/day) from January 2014 to September 2020 with an incident AE following treatment initiation. Ibr DR was defined as reduction of starting dose following the first reported incident AE. Demographics, clinical characteristics, time to first incident AE, TTNT, and Healthcare Resource Utilization (HCRU) were analyzed among pts with and without DR (time to event measured in months). TTNT was defined as time from first incident AE to initiation of a new agent (≤90 days of ibr discontinuation) or death and was compared in pts with and without DR using Kaplan-Meier analysis and a time-varying Cox proportional hazards model. Results: Of 3575 pts included in the analysis (median age: 76 years; male: 63.4%), 459 (12.8%) had a DR. Duration of 1L ibr, time to first incident AE, time to DR, and TTNT varied among study cohorts. Median TTNT (standard deviation [SD]) for pts with and without DR was 49.8 months (1.4) and 22.0 months (0.6), respectively. After 6 and 12 months of follow-up, significantly fewer pts with DR discontinued treatment than pts without DR (6 months: 8.3% vs 27.3%, P = 0.0062; 12 months: 13.8% vs 38.2%, P = 0.0003). A total of 51 pts discontinued treatment immediately after the first incident AE; 414 deaths were reported within 90 days of the first incident AE. After controlling for baseline demographics and clinical characteristics as well as time-varying HCRU and costs, pts with DR were not significantly likely to discontinue treatment compared with pts without DR (hazard ratio [95% CI], DR vs no DR: 0.89 [0.71–1.12]). Increased age, comorbidity index score, healthcare costs, and number of hospitalizations were significant predictors of treatment discontinuation. Conclusions: Among Medicare FFS pts with CLL/SLL and an AE following initiation of 1L ibr, pts with DR remained on therapy significantly longer than pts without DR. Ibr DR may be an effective strategy to manage tolerability while maintaining clinical efficacy.
Efficacy outcomes of treatments for double exposed chronic lymphocytic leukemia/small lymphocytic lymphoma: A systematic literature review.
Authors: Zuber Mohammed , Akkala Sreelatha , Ahmad Azeem , Villa Zapata Lorenzo
Published: June 2024

e19019

Background: Bruton's tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 inhibitor (BCL2i) venetoclax have improved outcomes and achieved durable remission in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) in both first-line and relapsed/refractory settings. Despite advances in treatment with these targeted agents, some CLL/SLL patients remain incurable. Notably, patients who fail to respond to both BTKis and venetoclax, termed 'double-exposed,' often exhibit poor outcomes. Data on treatment efficacy for this subgroup is limited. This study systematically reviews treatments and their efficacy outcomes in double-exposed CLL/SLL patients. Methods: A comprehensive search was conducted across MEDLINE/PubMed, Embase, and Web of Science databases from inception to November 2023, using relevant keywords and MeSH terms. The search focused on identifying studies reporting treatments and efficacy outcomes in double-exposed CLL/SLL patients, irrespective of discontinuation reasons. Key efficacy outcomes included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). Results: From 3942 retrieved articles, 12 publications covering 8 unique studies (4 clinical trials and 4 observational studies) were included. The median patient age ranged from 60-69 years in clinical trials to 56-76 years in observational studies. Two clinical trials reported PFS, with pirtobrutinib-treated patients showing a median PFS of 16.8 months (95% CI, 13.2-18.7) and lisocabtagene maraleucel-treated patients demonstrating a median PFS of 13 months (95% CI,2.8-not reached). BELLWAVE-001 was the sole study reporting a median OS of 10.1 months (95%CI, 7.4-15.9) in nemtabrutinib-treated patients. ORR varied, with 58% in nemtabrutinib-treated patients and 80% in those receiving lisocabtagene maraleucel. In the four observational studies, PFS ranged from 3 months (chemoimmunotherapy) to 12 months (BTKis), and ORR ranged from 31.8% (chemoimmunotherapy) to 85.7% (CAR T-cell therapy). Conclusions: This study underscores the scarcity of clinical data addressing efficacy outcomes in double-exposed CLL/SLL patients. Treatments like pirtobrutinib and CAR-T cell therapy show promise for this group. However, the limited treatment options and efficacy data following failure on BTKis and venetoclax highlight a significant unmet medical need. Further research is necessary to comprehensively understand efficacy outcomes in the double-exposed CLL/SLL population.
Rituximab, chidamide, and zanubrutinib (ZCR) ± CHOP as a regimen for treatment naive (TN) double-expressor DLBCL (DE-DLBCL).
Authors: Li Zhiming , Sun Peng , Jiang Yirong , Fu Xiangjun , Zhang Lu , Yang Hang
Published: June 2024

e19053

Background: DLBCL patients with co-expression of MYC (≥40%) and BCL2 (≥50%) by immunohistochemistry are considered as DE-DLBCL. The prognosis of DE-DLBCL is usually worse than DLBCL-NOS. The Smart Start trial had established the feasibility of chemotherapy-free targeted therapy before 1L chemotherapy. The BTK inhibitor Zanubrutinib (Z) or epigenetic drug Chidamide (C) with R-CHOP regimen has a potential synergistic effect in the treatment of DE-DLBCL. Under the inspiration of Smart Start, this trial aim to explore the feasibility of ZCR±CHOP regimen in TN DE-DLBCL. Methods: This is a multicenter, open-label, single-arm phase 2 study (NCT05527912) conducted in China. If patients achieve complete response (CR) after cycle-2 (C2), ZCR will be continued for up to 8 cycles. Otherwise, ZCR-CHOP will be given for another 6 cycles. The primary endpoint is CR rate at the end of treatment (CRR-EOT); secondary endpoints included ORR (overall response rate) ,2y-PFS, and 2y-OS. Plasma samples were collected at baseline, C2 and the EOT. In evaluable samples, circulating tumor DNA (ctDNA) assays were performed. Results: From February 2023 till now, 34 TN DE-DLBCL patients were enrolled, with 32 patients evaluable. The median age was 52y (range: 22-68), 55.9% were male, 79.4% were Non-GCB (Table 1). 12 patients who achieved CR by C2 were continued with RCZ chemo-free therapy, and CHOP were added to the 14 PR and 3 SD patients. In the 32 evaluable patients, ORR after C2 of RCZ was 81.25% (26/32, CR 37.5%, PR 43.75%, SD 9.4%, PD 9.4%). Up to now, 12 patients have completed 8 courses (C8) and all of them have achieved CR, both ORR and CR are 100% (12/12). 3 patients withdrew due to PD. For safety information in the trial, 64.3% patients reported grade (G)-3/4 AEs. In the Chemo-Free subgroup, only 4 patients (36.4%, 4/11) reported G-3/4 AEs. the majority of G-3/4 AEs is hematological events, including leukopenia, neutropenia and thrombocytopenia. The CR rate at C2 was 66.7% (6/9) in patients with negative baseline ctDNA results. The patients with BCL6 fusion of ctDNA at baseline were more prone to PD (3/4, 75.0%). Compared to baseline, plasma ctDNA levels decreased significantly after C2. 29 patients were evaluable for ctDNA after C2, 100% (12/12) of C2-CR patients and 58.8% (10/17) of non-C2-CR patients were negative, P=0.023. Compared with Non-C2-CR patients, the number of detected mutations and average VAF level were decreased in C2-CR patients. Conclusions: This trial demonstrates ZCR±CHOP could be a promising regimen with active antitumor effect and acceptable toxicity in TN DE-DLBCL patients. Clinical trial information: NCT05527912 .
Sex disparities in short-term outcomes among patients with diffuse large B cell lymphoma undergoing chimeric antigen receptor T-cell therapy in the United States.
Authors: Gadhiya Dhruvkumar , Adla Jala Saisree Reddy , Aggarwal Shruti , Sakthivel Hemamalini , Dhaliwal Kanwar Bir Singh , Ramphul Kamleshun , Sharma Shivani
Published: June 2024

e19062

Background: Chimeric Antigen Receptor (CAR) T-cell therapy, a promising immunotherapy used in various cancers, including Diffuse large B cell lymphoma (DLBCL), can involve multiple complications and the need for medical interventions. Our retrospective study strives to gain up-to-date insight into sex-based differences among DLBCL patients undergoing CAR T-cell therapy. Methods: We focussed on DLBCL patients undergoing CAR T-cell therapy via the 2017-2020 National Inpatient Sample(NIS). The events of complications between males and females were examined via multivariate regression models. Since the ICD-10 code for cytokine release syndrome (CRS) involved cases between October and December 2020, we used samples for that timeline while evaluating that particular complication. Results: Our study involved 3280 adult cases of DLBCL undergoing CAR T-cell therapy, with 1930 (58.8%) males and 1350(41.2%) females. Age differences were seen as females were older(mean age 61.93 vs. 60.40 years, p<0.01). Females also had lower odds of atrial fibrillation (6.7% vs. 14.2%, aOR 0.440, p<0.01) and acute kidney injury (AKI) (10.0% vs. 18.4%, aOR 0.458, p<0.01), while having higher odds of use of invasive mechanical ventilation (5.6% vs. 5.2%, aOR 2.179, p<0.01), events of sepsis (9.6% vs. 7.8%, aOR 1.575, p<0.01), pancytopenia (69.6% vs. 64.0%, aOR 1.454, p<0.01), and cryoprecipitate transfusion (2.2% vs. 1.8%, aOR 2.325, p=0.041) than males. We did not find any statistically significant differences for events of gastrointestinal bleeding (GIB)(aOR 0.866, p=0.636), tumor lysis syndrome(aOR 0.980, p=0.890), acute pulmonary embolism(aOR 1.133, p=0.719), toxic encephalopathy(aOR 1.009, p=0.935), platelet transfusion(aOR 0.994, p=0.976), RBC transfusion(aOR 0.828, p=0.192), or all-cause mortality(aOR 1.829, p=0.064). In addition, while 51.6% of males and 51.7% of females reported CRS, it was not statistically valid (aOR 0.923, p=0.850). Conclusions: The sex of DLBCL patients undergoing CAR T-cell therapy can influence multiple complications, as described in our study. Further research and endeavors aimed to deepen our understanding of our findings will help bring changes in protocols by physicians to improve the quality of care and outcomes of these patients.
Concordance between physician response assessment and a novel method per Lugano criteria in patients with lymphoma using real-world data.
Authors: Swain Richard Scott , Klink Andrew J. , Savill Kristin M. Zimmerman , Asgarisabet Parisa , Kalesan Bindu , Balanean Alexandrina , Hays Harlen , Kaufman Jill , McAllister Lindsay , Yu Hsing-Ting , Laney Jalyna R. , Richardson Nicholas C. , Lerro Catherine C. , Rizvi Fatima , Vallejo Jonathon , Wang Kun , Theoret Marc R. , Rivera Donna , Feinberg Bruce A.
Published: June 2024

e19082

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

e19501

Background: Cytotoxic chemotherapy for hematologic malignancies may adversely affect myelopoiesis, resulting in profound neutropenia that predisposes patients to severe infections. Patients undergoing hematopoietic stem cell transplantation (HSCT) are at particularly increased risk. Neutropenia is defined by an absolute neutrophil count (ANC) <500 cells/μL per complete blood count with differential. Neutropenic fever is a critical event with one-time temperature ≥101ºF or ≥100.4ºF sustained over one hour. Current standard-of-care is to initiate broad-spectrum antibacterial therapy within 30-60 minutes of presentation. MetroHealth Medical Center in Cleveland, Ohio launched a new Blood and Marrow Transplant program in 2023 in the state-of-the-art Glick Center. This retrospective study explores time to blood culture draw and initiation of antibiotics in HSCT patients with neutropenic fever. Methods: The MetroHealth HSCT database was used to identify hematologic malignancy patients status-post HSCT treated in the Blood and Marrow Transplant program. Tumor type and staging, chemo history, and infection prophylaxis (PPx) were recorded from chart review. Neutropenic fever episodes were identified by review of vitals history. Time to blood culture draw and antibiotic administration was then calculated from the medication administration record (MAR). Results: N = 11 hematologic malignancy patients status-post HSCT and chemotherapy were identified in the MetroHealth database. 8 presented with multiple myeloma (RISS stage II – IV), 2 with Hodgkin lymphoma, and 1 with mantle cell non-Hodgkin lymphoma. All patients were on Valtrex or acyclovir PPx, 10 on levofloxacin PPx, and 9 on fluconazole PPx. 6 of 11 patients had one documented episode of neutropenic fever each. ANC levels ranged from unidentifiable to 420 cells/μL. Half of the episodes saw blood culture draw within 1 hour and initiation of antibiotics in 60-90 minutes. The other 3 episodes saw culture draw at 2:13, 3:09, and 10:10 hours from fever and antibiotic administration at 12:00, 2:53, and 10:23 hours, respectively. Infectious disease (ID) specialists were consulted in each of the latter 3 cases. Conclusions: No patient at MetroHealth with neutropenic fever has seen appropriate initiation of antimicrobials within 30 to 60 minutes of presentation. Hypotheses for this delay include improper chart documentation, nurse training (delay in physician notification), and provider comfort (antimicrobials deferred to day team, ID consults). The latter is of particular concern given incidents of >10 hour delay to antibiotic initiation. Fortunately, there have not been any severe morbidity or mortality outcomes yet. Next steps are to deploy a quality improvement initiative to increase speed to fever identification, blood culture draw, and empiric antimicrobial delivery.
Patient-reported treatment-related symptoms and use of the PRO-CTCAE for multiple myeloma clinical trials: A qualitative interview study.
Authors: Kato Kelly , Mangrum Rikki , Gerould Heather , Schantz Karolina , Bryant Alexandra , Katz Eva , Gries Katharine
Published: June 2024

e19516

Background: Therapeutic regimens for multiple myeloma (MM) involve multiple pharmacological agents, including steroids. Many cause treatment-related symptoms that add to patient burden or may trigger treatment cessation. This study gathered qualitative data about the patient experience with MM treatments, including regimens with steroids. Findings were summarized and compared to the Patient Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), to assess its comprehensiveness and relevance in MM clinical trials. Methods: Individual, semi-structured interviews were conducted virtually with a diverse sample of 16 US-based, English-speaking adults (38% male, 25% Black, 13% Hispanic) to explore their experiences with MM and treatments, including perspectives on steroids and potential benefits of steroid-sparing regimens. Content analysis was used to summarize and compare terminology participants used to describe their experiences with treatments. Results: Participants reported a diverse set of treatment-related symptoms impacting their overall experience, indicating the importance of assessing regimen tolerability in clinical trials. Steroids were linked to increased energy that interfered with sleep or functioning, irritability, taste changes, weight gain, increased appetite, and cognitive symptoms like brain fog. Participants reported that most symptoms were tolerable, but they would prefer to avoid steroids if treatment benefits did not diminish. Many reported symptoms were included in the PRO-CTCAE items (see Table), but several symptoms related to regimens with steroids are not covered: excess energy, bitter/metallic taste, taste sensitivity, brittle nails, irritability, hunger/increased appetite, and muscle weakness. Conclusions: MM patients experience a range of treatment-related symptoms, many of which impact their quality of life. If given the option, patients would prefer a steroid-free regimen if there was proven clinical benefit. While the PRO-CTCAE covers most of the treatment-related symptoms, proving to be an option for multiple myeloma clinical trials, additional PRO instruments may be needed to cover specific gaps in the PRO-CTCAE item library content coverage. [Table: see text]
Hospitalizations for multiple myeloma in the United States from 2011 to 2019: An analysis of trends and disparities.
Authors: Solangi Zeeshan , Agudile Emeka , Kumar Arun , Shah Ghulam , Devi Amirta , Yalcin Yusuf , Solangi Ahda , Kozyreva Olga N. , Evanchuk Darren M.
Published: June 2024

e19519

Background: The incidence and mortality rates of multiple myeloma have been increasing in recent decades, particularly among older adults. Understanding the trends and disparities in hospitalizations for this disease is crucial for informing healthcare resource allocation and improving patient outcomes. Methods: Our study examined trends and disparities in hospitalization for multiple myeloma, plasmacytoma and plasma cell leukemia in the US from 2011 to 2019, utilizing data from the Nationwide Inpatient Sample (NIS) database. We focused on patients aged 18 and above with specific ICD diagnosis codes. Our main objectives included analyzing admission numbers, discharge rates, length of stay, hospitalization costs, and mortality rates, using Stata version 15.1. Appropriate discharge weights were used in the analysis to address critical elements of sampling design, and a p-value of <0.05 was deemed statistically significant. Results: Overall, there was a significant increase in both the absolute number and frequency of admissions from 20,584 in 2011 to 25,373 in 2019 (P < 0.001), while the length of stay remained stable at 5.8 days in 2011 and 6.1 days in 2019. Hospitalization costs also rose significantly, with mean charges per patient increasing by 36.3% from $72,680.65 in 2011 to $99,065.22 in 2019 (P < 0.001). The total aggregate cost for hospitalizations with multiple myeloma as the discharge diagnosis increased from $1.50 billion in 2011 to $2.51 billion in 2019 (inflation adjusted) (P < 0.001). Although the absolute number of mortality cases increased from 2011 to 2019, there was a significant decrease in mortality rate over the same period from 5.7% in 2011 to 4.8% in 2019 (P < 0.001). Analyses uncovered disparities in hospitalizations across various demographics such as age, race/ethnicity, payer type, income, and hospital characteristics. The 65-84 age group exhibited the highest increase in discharge rates (31%), followed by the 45-64 group (13.9%), with all age groups except 18-44 showing increases. African-Americans had the highest frequency of discharges, followed by Hispanics and Asian/Pacific Islanders. While White patients had the highest absolute numbers of multiple myeloma discharges, their increase in discharge frequency was not statistically significant. Discharge frequency rose for all payer groups, with the largest increase seen among medicare patients. Disparities were also observed based on income, with the greatest increase in the 51st-75th percentile income group. Urban teaching hospitals had the highest absolute number and frequency of discharges, followed by urban non-teaching and rural hospitals. Conclusions: These findings highlight the rising burden of multiple myeloma hospitalizations in the United States and underscore the need to address existing disparities in access to care and treatment outcomes.