bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating costs of adverse events (AEs) and healthcare resource use (HRU) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) receiving tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel): A summary of real-world evidence.
Authors: Yang Hongbo , Qi Cynthia Zhengyun , Dalal Anand , Bollu Vamsi , Zhang Jie , Zhang Su , Lim Stephen 
Published: June 2021

e19551 Background: The AE rates and HRU reported in multiple real-world evidence (RWE) studies of chimeric antigen receptor T-cell (CAR-T) therapies tisa-cel and axi-cel in r/r DLBCL have differed from those in their clinical trials. However, the cost implications from these findings are not well understood in existing literature. This study summarizes information from these RWE studies of tisa-cel and axi-cel and quantifies the associated costs. Methods: A literature review was conducted to identify RWE studies reporting AE rates and HRU of tisa-cel and axi-cel in the United States (US). AE rates and HRU were summarized and the associated costs were estimated using a micro-costing approach. Costs of AE management included hospitalization and pharmacy costs, such as intensive care unit (ICU) stays, inpatient admissions, and medications for the treatment of cytokine release syndrome (CRS) and neurotoxicity events (NE). HRU costs included hospitalization, ICU stays, and outpatient visit costs. Unit costs were from public health databases that are representative of US healthcare system and from literature. Costs were inflated to 2020 US dollars. A range was reported to present evidence if inputs are available from multiple studies. Results were summarized for tisa-cel and axi-cel separately. Results: Four publications were identified: Jaglowski 2019, Pasquini 2019, Riedell 2019, and Jacobson 2020. Across studies, grade 3+ CRS and NE occurred in 1%-4% and 0%-5% of tisa-cel-treated patients and 7%-16% and 20%-35% of axi-cel-treated patients, respectively. Tocilizumab usage was reported in 14%-20% of tisa-cel- and 62%-71% of axi-cel-treated patients. CAR-T infusion was inpatient for 36% of tisa-cel- and 92%-100% of axi-cel-treated patients. The median hospitalization days was 2 for tisa-cel and 15-16 for axi-cel. ICU transfer was observed for 7% and 28%-38% of tisa-cel- and axi-cel-treated patients, respectively, with median stays of 4 and 5 days, respectively. The median number of outpatient visits within 28 days after infusion was 6 for tisa-cel and 4 for axi-cel. The total estimated costs for managing AEs per patient were $843-$1,962 for tisa-cel and $5,979-$10,878 for axi-cel. The total estimated HRU costs per patient were $3,321 for tisa-cel and $32,394-33,166 for axi-cel. Conclusions: RWE studies suggest that patients with r/r DLBCL receiving tisa-cel had numerically lower AE rates, HRU, and cost burden than those receiving axi-cel in the US. The additional cost burden for axi-cel was primarily driven by the incremental ICU and hospitalization care due to a higher proportion of inpatient infusion among patients receiving axi-cel. Further research is warranted to compare the costs associated with the two CAR-Ts in r/r DLBCL.
Effectiveness of intravenous high-dose methotrexate for prevention of relapse in patients with DLBCL.
Authors: Alotaibi Hind , Motabi Ibraheem , Butt Ahmad , AlShehry Nawal , Marei Mohammed , Tailor Imran , Altaf Sayed , Zaidi Syed , Alnoamani Mohammed , Alrajhi Abdullah , Albtoosh Bilal , Alzahrani Kamal , Alfayez Mansour 
Published: June 2021

e19562 Background: Central nervous system (CNS) relapse develops in 2-10% of patients with diffuse large B cell lymphoma (DLBCL) and has an adverse prognosis. Tools like IPI and CNS-IPI scores identify patients at high risk of systemic or CNS relapse based on the presence of established risk factors ( Schmitz et al. JCO 2016). International guidelines propose prophylactic intravenous high-dose methotrexate (HD-MTX) for patients at high risk of CNS relapse; however, limited data is backing this approach. Methods: We conducted a retrospective review of newly diagnosed DLBCL patients aged 18-75 years treated with curative intent at large academic medical centers in Riyadh, Saudi Arabia, between 2015-2018. Patients who were planned for CNS HD-MTX after cycles 2, 4, and 6 of R-CHOP and received at least one HD-MTX cycle were included. Results: We identified 35 DLBCL patients who received at least one R-CHOP cycle with one cycle of HD-MTX. The median IPI and CNS-IPI score were 3, (range = 0-4) and 3, (range = 0-5), respectively. The median number of R-CHOP cycles received was 6 (range 3-6) and HD-MTX 3 (range 1-6). The overall response rate was 91%, with 3 (9%) primary refractory patients per interim evaluation on cycle 3 of R-CHOP. Achieving complete remission after six cycles of RCHOP was noted in 80%, with four additional patients showed residual disease at the end of treatment evaluation. The entire cohort's overall survival was not reached, and five years estimated survival is 75%. With a median follow-up duration of 37.3 months, none of the patients relapsed after achieving CR at the end of treatment evaluation. The risk of systemic or CNS relapse in our cohort was 0%. In restricting the analysis to CNS-IPI of ≥ 4, a total of 13 patients with a median follow-up of 42 months were included; four patients did not achieve CR by the end of treatment, while nine patients continue to be in CR without any evidence of relapsed disease. Conclusions: High-dose methotrexate with high-intensity chemoimmunotherapy (R-CHOP) seems to be associated with an improvement in the expected rate of CNS relapse. Our data set is small, and a more extensive study evaluating HD-MTX's effectiveness in high-risk DLBCL is warranted.[Table: see text]
Chemotherapy-based stem cell mobilization in multiple myeloma patients treated with novel agents: The Mayo Clinic experience.
Authors: Vaxman Iuliana , Muchtar Eli , Kapoor Prashant , Kumar Shaji , Dispenzieri Angela , Buadi Francis , Dingli David , Gonsalves Wilson I. , Kourelis Taxiarchis , Warsame Rahma M. , Lacy Martha , Hogan William J. , Gertz Morie A. 
Published: June 2021

e20000 Background: In the novel agents’ era, refractoriness to induction in Multiple Myeloma (MM) is relatively rare. This population remain an unmet need and are often excluded from clinical trials. In the current era, chemotherapy-induced stem cell collections are used at Mayo Clinic in “poor responders” to induction, such as patients that progress prior to ASCT or patients with significant disease burden after induction. Methods: This is a retrospective study that includes all MM patients the underwent chemo-mobilization between January 2012 and September 2020 at Mayo Clinic. We compared our cohort to a cohort of 125 matched patients that were transplanted over the same time period and underwent mobilization with G-CSF and “on-demand” plerixafor. We matched the cohorts by level of response by IMWG at pre-transplant evaluation. Results: 125 newly diagnosed MM patients who received novel agents’ induction and had a poor response to induction were mobilized using IV intermediate-dose cyclophosphamide (83%) or VDT-PACE (17%) plus G-CSF and “on-demand” plerixafor. The median PFS and OS of the chemo-mobilized cohort were 16 months (95% CI 11-20) and 47 months (95% CI 37-71), respectively. Patients receiving chemo-mobilization had higher stem cell yields than the growth factor only cohort (median 9.88X106 cells/kg versus median 8.77X106 cells/kg, respectively (P<0.001)). The safety profile of chemo-mobilization was favorable, with no difference between the two groups in length of hospitalization during ASCT (P=0.95), days to neutrophil or platelet engraftment, and risk of bacteremia (P=0.38). 29% of the chemo-mobilized cohort and 66% of the matched cohort required plerixafor for adequate mobilization (P<0.001). Conclusions: Chemo-mobilization enhances stem cell collection in MM patients with a suboptimal response to induction and reduces the need for plerixafor without adversely impacting the post-transplant clinical course. [Table: see text]
Outcomes of patients with multiple myeloma treated at a regional Australian center compared to a metropolitan Australian center.
Authors: Ai Sylvia , Kang Sharlyn , Presgrave Peter , Cartwright Kim , Warburton Pauline , Desai Shrinivas , Parmar Gurdeep 
Published: June 2021

e20003 Background: A number of studies have demonstrated poorer outcomes for patients with cancer who live in rural/regional areas compared to metropolitan areas. There is conflicting information on the effect of rurality on outcomes of patients with multiple myeloma, and limited information regarding the cause of this discrepancy. Methods: Retrospective analysis of demographic, treatment and outcomes of 238 patients newly diagnosed with multiple myeloma between 2002-2019 in the Illawara Shoalhaven Local Health District. Results: Patients being treated in a regional cancer care centre had lower overall survival compared to those treated at a metropolitan cancer care centre (median OS = 63.6 months vs. 43.8 months, p=0.004), and a trend towards lower progression-free survival (median PFS = 24.7 months vs. 19.8 months, p=0.228) despite treatment by the same group of hematologists. There was a lower rate of autologous transplantation for patients treated at a regional cancer care centre compared to a metropolitan cancer care centre (36% vs. 18%, p=0.007). Conclusions: Survival differences between patients with multiple myeloma living in regional areas compared to metropolitan areas may be due to lower rates of autologous transplantation.
Tandem versus single autologous stem cell transplant: A patient-reported outcome.
Authors: Molina Thomas H. , Sweeney Nathan W. , Cole Nolan , Ahlstrom Jenny 
Published: June 2021

e20026 Background: Whether tandem autologous stem cell transplant (ASCT) is superior to single ASCT for new diagnosed multiple myeloma (MM) patients remains a subject of discussion in the era of novel agents. This project analyzed patient-reported outcomes to single ASCT and tandem ASCT utilizing an online patient-centered platform. Methods: We analyzed patient-reported treatment outcomes pertaining to tandem ASCT and single ASCT from HealthTree Cure Hub ( www.healthtree.org ). In this study, we examined whether patients reported a reduction or no reduction in their myeloma after their tandem or single ASCT. The association between stem cell transplant and myeloma outcome was compared by chi-squared test. Results: In this retrospective analysis of 945 MM patients, we compared two groups, those that reported receiving a tandem ASCT (n = 75) and those that reported receiving a single ASCT (n = 870). Our analysis revealed an association between patients who reported receiving a tandem ASCT and a reduction of their myeloma (chi-square (1) = 3.87, p = .04), compared to patients who reported receiving a single ASCT. Conclusions: Tandem ASCT was perceived by patients to be superior over single ASCT in regard to myeloma reduction for the HealthTree patient population. A more in-depth analysis of the patient-provided health data from HealthTree could aid in determining factors related to survival as well as help to quickly answer lingering questions related to tandem ASCT, such as timing, genetic factors, progression free survival, and more.[Table: see text]
Characterization of smoldering multiple myeloma: A population-based cohort study.
Authors: Fatoki Raleigh Ayoolu , Khan Adnan Ahmed , Carpenter Diane M. , Baer David M. 
Published: June 2021

e20028 Background: There is increasing interest in characterizing Smoldering Multiple Myeloma (SMM) due to the availability of novel therapies shown to delay symptomatic progression to Multiple Myeloma (MM) with considerably less toxicity. The lack of population-based disease registries has made epidemiologic data on SMM difficult to acquire. Existing cohort studies of SMM patients have largely been conducted in specialized referral centers. This surveillance study characterizes the epidemiology of SMM in a real-world, clinical population using data from a large, integrated healthcare delivery system. Methods: We performed a retrospective study of all new SMM cases identified in Kaiser Permanente Northern California (KPNC) during 2010-2017, based on either (or (2) a new MM diagnosis in the KPNC Cancer Registry without initiation of plasma cell-directed therapy within 1 year of diagnosis. Those without KPNC membership for at least 1 year after diagnosis were excluded. Age at diagnosis, sex, race/ethnicity, and Charlson Comorbidity Index (CCI) at diagnosis were examined. The incidence of SMM was calculated using KPNC membership denominators, and a 2-sided Cochran-Armitage test was used to test for trend. Among the SMM cohort, characteristics were examined using the chi-squared test, including data before/after the Nov 2014 International Myeloma Working Group (IMWG) diagnostic criteria update. Results: A total of 251 new SMM cases were identified from 2010-2017. The average annual incidence of SMM was 1.2 per 100,000, increasing from 1.0 per 100,000 in 2010 to 1.5 per 100,000 in 2017 (p<0.05 for trend). The demographic characteristics of the SMM cohort were notable for mean age 70.0 ± 11.7 years, 63.8% male, and 61.0% non-Hispanic White, 17.1% Black, 10.0% Hispanic, and 11.6% Asian. Overall, 73.7% had at least 1 comorbidity, based on CCI. When comparing 116 SMM cases diagnosed after the IMWG update to 135 cases diagnosed before the IMWG update, those diagnosed after the revised IMWG guidelines were significantly more likely to have at least 1 existing comorbidity (80.2% vs 68.2%, p=0.03). Conclusion We identified a contemporary cohort of patients with SMM from a large, integrated healthcare system. During our 8-year study period, the annual incidence of SMM increased slightly, including after 2014 when the IMWG criteria for SMM were refined. We observed that patients diagnosed after the 2014 IMWG update were more likely to have at least 1 comorbidity. Whether these trends relate to background population characteristics or are specific to recognized SMM cases bears further study. Follow-up analyses will examine the rate of progression from SMM to MM and the presence or absence of severe, irreversible, end-organ damage at the time of progression.
Association of kappa light chain restriction with peripheral neuropathy among patients with non-IgM monoclonal gammopathy of undetermined significance.
Authors: Dasanu Constantin A. , Kaur Jaspreet , Tuler Shahaf , Farrell Stephanie , Plaxe Steven C. 
Published: June 2021

e20040 Background: Monoclonal gammopathy of undetermined significance (MGUS) can be associated with significant neurologic morbidity. Of non-IgM MGUS, types IgG and IgA are most commonly associated with peripheral neuropathy (PN). Methods: With IRB approval, we conducted a retrospective cohort study of consecutive patients with non-IgM type MGUS treated at our institution from 2014-2021. Other conditions potentially causing PN were excluded. Statistical analysis: Descriptive statistics were calculated to characterize the study population, and Relative Risk (RR) of PN was evaluated for selected patient, and disease, related factors. P < 0.05 was defined as statistically significant. Results: During the study period, 94 patients with non-IgM type MGUS were seen and comprised the study population. Twenty-two (23.4%) had evidence of PN. Median age was 74; 82% (18/22 ) were Caucasian; 73% (16/22) were women. 82% (18/22) patients had MGUS type IgG kappa or IgA kappa. We identified only 2 patients with each MGUS kappa light chain (LC) and MGUS IgG lambda. Median M-protein size was 0.11 g/dL, and median free LC value was 6.84 mg/L. Incidence/severity of kidney disease was similar in non-IgM MGUS patients with and without PN (p > 0.05). RR of PN was not found to be significantly different based on race or gender, although there appeared to be a tendency for women to be at higher risk compared to men (RR = 1.98, 95% CI = 0.85 to 4.60, p = 0.114.) Kappa LC restriction was strongly associated with PN (RR = 4.31, 95% CI = 1.58 to 11.78; p = 0.004). Electromyographic (EMG) studies identified 14 patients (64%) with distal symmetric axonal neuropathy (DSAN) and 8 patients (36%) with chronic inflammatory demyelinating polyneuropathy (CIDP). Clinically severe PN was identified in 11 (50%) patients; all were subsequently treated with IVIg therapy. Only 5/11 (45%) patients responded to IVIg, and the responses were only partial and transient. Conclusions: This is the first report, to our knowledge, of a significant association of kappa (as opposed to lambda) LC restriction with PN among patients with non-IgM type MGUS. Further investigation is warranted to explain this finding, elucidate pathophysiology and aid in developing more effective therapeutic options. Pending mechanistic characterization of this association, trials of contemporary agents used to treat other plasma cell disorders may be in order. Final statistical analysis, comparison to published series and significance will be presented.
Real-world prognostic model for malignant pleural mesothelioma.
Authors: Nasser Abdullah , Baird Andrew , Saint-Pierre Mathieu D. , Laurie Scott A. , Wheatley-Price Paul 
Published: June 2021

e20562 Background: Two mesothelioma prognostic models have been suggested: European Organisation for Research and Treatment of Cancer (EORTC) and Cancer and Leukaemia Group B (CALGB) models. Both were based on clinical trial patients enrolled in the mid-1980s to early-1990s. Several changes to mesothelioma management have been adopted since publication of these models, including improved surgical and palliative interventions and changes to systemic therapy. Methods: With ethics approval, we collected and analyzed the health data of malignant pleural mesothelioma (MPM) patients with histologically confirmed diagnosis treated at our institution between January 1991 and March 2019. The primary endpoint was overall survival (OS). Univariate analysis was used to identify significant predictors of survival, which were then used to construct a multivariate survival tree with complete case-analysis and bootstrapping. Patients were then stratified into three prognostic groups based on their median OS. Results: 337 patients were included in the study; 309 (91.7%) were dead at last follow-up. The median OS was 9.4 (8.1-11.5) months for the entire population. Eastern Cooperative Oncology Group (ECOG) performance status (PS), histology, white blood count, platelets, International Mesothelioma Interest Group stage, age and hemoglobin were independent predictors of survival. The final pruned survival tree was based on 285 patients and incorporated the first five predictors. Good, intermediate and poor prognostic groups had median OS of > 12 months, 6-12 months, and < 6 months, respectively. Factors associated with the prognostic groups were: good prognosis: ECOG 0-1, normal platelets, stage 1, 2 and epithelioid histology; intermediate prognosis: ECOG 0-1 with either stage 3, 4 and/or sarcomatoid or biphasic histology; poor prognosis: ECOG 2-4 regardless of other factors. Conclusions: In contrast to EORTC/CALGB, real world evidence generates these prognostic groups with face validity but will need independent validation. Our data does not account for recent advances including immunotherapy, and thus patients with non-epithelioid histology may have better survival than predicted.[Table: see text]
Effects of trilaciclib prior to chemotherapy ± atezolizumab on T-cell activation in patients with newly diagnosed extensive-stage small cell lung cancer.
Authors: Stevens Aaron D. , Daniel Davey B. , Goldschmidt Jerome H. , Fields Paul A. , Banbury Barb , Wolfe Steven , Glass Jarrett , Horton Janet K. , Sorrentino Jessica 
Published: June 2021

e20582 Background: Chemotherapy ± immunotherapy has demonstrated meaningful clinical benefit to patients (pts) with extensive-stage small cell lung cancer (ES-SCLC); however, chemotherapy-induced damage to the immune system can potentially diminish treatment efficacy. Trilaciclib (T) is an intravenous cyclin-dependent kinase 4/6 inhibitor that protects hematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection) and may directly enhance antitumor immunity. Here, we evaluated the immune effects of T in pts with ES-SCLC receiving T or placebo (P) prior to first-line etoposide plus carboplatin (E/C) or E/C plus atezolizumab (E/C/A) in two phase 2 clinical trials. Methods: Genomic DNA, extracted from peripheral blood mononuclear cells (baseline and on treatment) and archival tumor tissue (baseline), was analyzed using the immunoSEQ® Assay (Adaptive Biotechnologies). T-cell receptor (TCR) β CDR3 regions were amplified and sequenced to identify and quantitate the abundance of each unique TCRβ CDR3. Clonal frequencies were compared at baseline and on treatment, and statistical differences between T and P were determined by Wilcoxon rank sum test. Antitumor response was defined as complete/partial response. Results: In both studies, peripheral T-cell clonal expansion was greater among pts receiving T versus P. Among pts receiving E/C, those in the T/E/C group with an antitumor response had significantly more peripheral clonal expansion than P responders (median 23 vs 12 clones; P= 0.04) and a greater number of tumor-associated expanded clones ( P= 0.03). T responders had more newly detected expanded peripheral clones compared with P responders (6 vs 1.5 clones; P= 0.06) and T nonresponders ( P= 0.02). Increased clonal expansion in T responders was more evident after two cycles of E/C versus four, suggesting that T results in a rapid T-cell response. Similarly, among pts receiving E/C/A, those in the T/E/C/A group with an antitumor response had significantly more peripheral clonal expansion than P responders (median 90 vs 43 clones; P= 0.002) and T nonresponders ( P= 0.016). T responders also had more newly expanded peripheral clones compared with P responders (68 vs 11 clones; P= 0.003) and T nonresponders ( P= 0.02). There was no increase in tumor-associated expanded clones among T responders compared to P responders, possibly due to the time point at which clonal expansion was assessed (after four cycles) or the addition of atezolizumab. Associations between peripheral and tumor-associated clonal expansion and survival will be presented. Conclusions: The data suggest that, among pts treated with T/E/C or T/E/C/A, increased clonal expansion is associated with clinical response, indicating that T may enhance antitumor immunity in pts with ES-SCLC treated with chemotherapy.