bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.