bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world outcomes of venetoclax refractory multiple myeloma patients.
Authors: Maples Kathryn T. , Kaufman Jonathan L. , Gupta Vikas Anand , Joseph Nisha , Heffner Leonard T. , Hofmeister Craig C. , Dhodapkar Madhav V. , Matulis Shannon M. , Boise Lawrence , Lonial Sagar , Nooka Ajay K. 
Published: May 2020

e20524 Background: The BELLINI trial investigated the efficacy and safety of venetoclax (ven)/bortezomib (bort)/dexamethasone (dex) vs placebo/bort/dex in patients with bort-sensitive, early relapsed myeloma. The median PFS favored the ven arm (22.4 vs 11.5 months); however, a higher death rate in the ven arm led to study discontinuation. A subgroup of patients with t(11;14) not only had improved PFS but a positive trend in OS with ven, suggesting biomarker-driven patient selection may mitigate the safety concern. BELLIINI results raised concern regarding the natural history of myeloma progressing on ven. We aimed to investigate the clinical outcomes of ven refractory myeloma patients. Methods: We identified 70 refractory myeloma patients at our institution prescribed ven alone or in combination between 03/2014 -11/2019. Our group has published the functional profiling of BCL2 family members to predict responses to ven (Matulis, S et al. Leukemia), and most patients had functional profiling available prior to starting ven. Demographic and outcomes data were obtained from our IRB approved myeloma database and responses were evaluated per IMWG criteria. Results: Patients received a median of 3 (1-13) lines of therapy (LOT), with 37% receiving ≥4prior LOT and 86% had t(11;14) by FISH/CTG. Most patients received ASCT (86%) and were refractory to len and bort (97%), dara (41.4%), car (43%), or pom (53%). The most common combinations with ven were dex (83%), PI and dex (8.5%), or dara and dex (8.5%). At a median follow up of 16.8 months, 38 patients progressed on ven. Median duration of therapy was 9.5 (1-63) months. Median PFS for the entire cohort was 13 (7.9-18.2) months. Use of ven as an early LOT provided PFS benefit ( < 3 vs > 3 LOT: 23.2 vs 10.4 months). Notably, patients who received > 6 LOT also had a PFS benefit of 7.23 (0-15.6) months, and ‘penta-refractory’ patients had a PFS of 7.2 (0-17.2) months. Among the 38 patients that progressed on ven, dara-based combinations (30%) and clinical trials (24%) were the most common subsequent LOT. At a median follow up of 15.4 months, the median OS for the cohort from the time of ven refractoriness was 31.4 months. Patients who received > 6 LOT had an OS of 15.1 (0-14.2) months and ‘penta-refractory’ patients at ven refractoriness had an OS of 13.7 (0-30.6) months. Conclusions: Patients with ven refractory myeloma can still experience good long term outcomes, and our experience does not support the hypothesis that ven resistance leads to a more refractory myeloma phenotype. These data support the early use of ven or ven combinations in the t(11;14) cohort of patients.
DREAMM-1 Patient perspectives from the first-in-human study of single-agent belantamab mafodotin for relapsed and refractory multiple myeloma (RRMM).
Authors: Eliason Laurie , Opalinska Joanna , Martin Mona L. , Correll Julia , Gutierrez Benjamin , Popat Rakesh 
Published: May 2020

e20531 Background: Patient-reported outcomes in RRMM remain poor, particularly for those refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies, and there is an increased risk of cumulative toxicities in these patients. Single-agent belantamab mafodotin (GSK2857916), a first-in-class, B-cell maturation antigen–binding immunoconjugate, has demonstrated deep and durable responses with a manageable safety profile in heavily pretreated patients with RRMM (DREAMM-1, NCT02064387). Here, we present patient-reported clinical benefit/tolerability of belantamab mafodotin evaluated by trial-embedded end-of-treatment (EOT) and follow-up interviews. Methods: DREAMM-1 study design and results have been reported ( Blood Cancer J 2019). Patients in the Part 2 expansion phase were administered single-agent belantamab mafodotin 3.4 mg/kg IV once every 3 weeks for 16 cycles and invited to participate in interviews at EOT and 6-month follow-up. Patients discussed symptoms, treatment-related adverse events (AEs), treatment burden, and overall treatment satisfaction, rated 0–10 (0 = not severe to 10 = most severe/0 = not at all satisfied to 10 = extremely satisfied). Results: A total of 17/35 patients (9 female [53%]) were interviewed; 4/17 patients completed both interviews. Most patients (94%; 16/17) achieved a partial response or better. At EOT, patients reported an improvement from the worst point in symptoms of bone pain (mean change in score from 6.4 to 4.0) and fatigue (8.0 to 5.5). The most commonly reported treatment-related AE was blurred vision (76%; 13/17). Among those reporting this AE, 62% (8/13) reported resolution or steady improvement in vision after EOT; with a reduction in severity rating from 7.3 at worst to 5.3 at EOT for this event. Most patients (93%; 13/14) never considered stopping treatment owing to AEs, including ocular events. Overall treatment satisfaction was high (mean score 7.9; median 9.0). Conclusions: Despite small sample sizes, trial-embedded interviews provide valuable insight into patient experience with belantamab mafodotin. Patients treated with single-agent belantamab mafodotin reported high treatment satisfaction and improvements in symptoms. Visual symptoms were frequent but manageable, and improved or resolved after treatment. Funding: GlaxoSmithKline (117159). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT02064387.
The impact of first-line therapy with novel agents in multiple myeloma patients age 80 and above: A systematic review.
Authors: Rahman Sadaf , Sider Cody , Bahodi Fadi , Lam Selay , Louzada Martha , Phua Chai W. 
Published: May 2020

e20532 Background: Novel therapeutic agents in multiple myeloma (MM) have demonstrated significant improvements in treatment outcomes. However, data remains scarce in newly diagnosed transplant-ineligible patients aged 80 and above as they are less represented in clinical trials. Optimal treatment of this population also proves challenging due to treatment-related adverse events. Methods: MEDLINE and EMBASE search concluded March 4, 2019. We included studies that evaluated first-line treatment of age ≥80 transplant-ineligible MM patients with novel agents. The primary outcomes assessed were OS and PFS. A qualitative analysis was undertaken due to the small number of included articles. Results: Of 1683 articles assessed for eligibility, 134 articles proceeded to full-text review. 6 articles with a total of 819 patients age ≥ 80 (range 80-96) were included for analysis (5 retrospective analyses and 1 phase II, non-randomized trial). Median OS were significantly shorter in age ≥80 in comparison to younger groups (reported median OS ranged from 19.5-31.9mo for age ≥80, 46-54.8mo for age 66-79, and 81-83.8mo or not reached for age ≤65). Shorter survival was associated with poorer performance status, advanced ISS stage, higher Charlson Comorbidity Index, anemia and elevated serum LDH. In one study, attaining a very good partial response or better (≥VGPR) was associated with improved median OS (30.4mo vs 18.8mo, p = 0.001). There was no difference between age groups for OS if ≥ VGPR was attained (53.4mo in age ≥80, vs not reached in age 66-79 or age ≤65; p = 0.184). In 1 of 3 studies that reported median PFS, a significant difference in one study was noted by age [age ≥80 = 19.1mo, age 66-79 = 26.3mo (p = 0.033), ≤65 = 54.3mo (p = 0.0009)]. Early mortality (at 2 or 6 months; in 3 studies) was significantly greater than in patients age < 80 and was primarily due to infection or renal failure, and more often in the frail. One study noted that despite reduced OS, the relative survival rate was higher in patients aged ≥85 at 2 years than in younger age groups. Conclusions: Our review excluded most RCTs as subgroup analyses of patients aged ≥80 were not available. Regardless, included articles are representative of the real-world experience. This systematic review suggests that while MM patients aged ≥80 experience shorter OS and PFS, treatment with a novel agent may offer comparable survival outcomes to younger groups in those able to attain ≥VGPR. Relative survival in elderly patients also favours active treatment in this age group, while balancing the risks of early mortality.
Adverse event and outcome patterns in patients with advanced multiple myeloma in the United States.
Authors: Richter Joshua Ryan , Yeaw Jason , Shah Drishti , Anupindi Ruthwik , Kudaravalli Suneel , Zavisic Stojan 
Published: May 2020

e20544 Background: Multiple Myeloma (MM) is a hematologic malignancy with an estimated 5-year survival rate of just over 50%. Evolving paradigms arising from numerous FDA approvals continue to shape the treatment landscape for relapsed and refractory MM (RRMM) patients. As the number of approved drugs/regimens increases, the efficacy as well as toxicity profiles for the more heavily refractory patient change. The objective of this study was to evaluate adverse event rates and associated outcome patterns among RRMM patients treated with pomalidomide (poma) or daratumumab (dara). Methods: Adult patients with ≥1 claim of poma or dara (index) were identified between Jan 1, 2012 and Feb 28, 2018 using IQVIA’s Real-World Adjudicated US claims database. Patients were required to be continuously enrolled in the health plan ≥180 days prior and ≥360 days post index date, have a diagnosis or treatment claim for MM and a claim of any immunomodulatory drugs and proteasome inhibitors before index date. Mean time to new therapy and mean time to readmission were evaluated over the 1-year post-index period among RRMM patients. Overall survival (OS) was measured using Kaplan-Meier curves. Occurrences of adverse events (AEs) and mean length of stay for AE-related hospitalization were also reported. Results: There were 289 patients in the RRMM cohort with 67.8% of patients treated with combination therapy in the baseline period. Of index therapies, 81% of patients used poma and 40% used dara in post-index period. Overall, 42% of patients had a Charlson Comorbidity Score of ≥3. Among 258 patients with a new treatment post-index, mean (SD) time to a new treatment was 4.7(5.3) months. Median OS was 14.6 months. Post-index hematological AE were frequent such as anemia (72.0%), febrile neutropenia (52.6%), neutropenia (30.1%) and thrombocytopenia (36.0%, Table). Mean length of stay for AE-related hospitalizations was 10.1 days and mean time to readmission was 63.3 days. Conclusions: Low OS, high frequency of AEs and longer LOS for AE-related hospitalizations suggest that outcomes of these patients remain poor despite availability of newer treatment options. Further study is warranted to better manage the individual and system-wide toxicity in this clinical setting. [Table: see text]
Preclinical evaluation of TQB3602, a small molecule proteasome inhibitor clinical candidate.
Authors: Zhang Xiquan , Yang Ling , Tian Xin , He Lihua , Xiong Jian , Niu Xiaoxia , Xia Yuanfeng , Li Jian , Chen Shuhui , Chen Kevin 
Published: May 2020

e20546 Background: Proteasome inhibitors, selectively inhibit the activity of proteasome in ubiquitin proteasome system, together with immunomodulatory drugs formed the basis of many treatment regimens for multiple myeloma in first-line therapy as well as for the treatment of relapsed disease. Bortezomib (Velcade), the first approved therapeutic proteasome inhibitor with a unique boronic acid as warhead, limited by its requirement for parenteral administration (intravenous or subcutaneous). The 2nd generation boronic acid – orally bioavailable Ixazomib (Ninlaro) was approved in 2015 by FDA greatly improved patient’s compliance. However, its adverse effect remained an issue in clinical application. The purpose of this study is to investigate the in vitro and in vivo antitumor activity of TQB3602, a novel orally bioavailable small molecule proteasome inhibitor, in preclinical models of multiple myeloma. Methods: The enzyme inhibition and anti-proliferative activity of TQB3602 was evaluated in 20S proteasome and MM.1S cell line. Oral administration of TQB3602 at 3 doses was used to evaluate the in vivo anti-tumor activity in MM.1S multiple myeloma xenograft (CDX) models. Results: TQB3602 displayed potent kinase inhibiting activity for 20S proteasome enzyme with IC50 15.3 nM. TQB3602 inhibited cell proliferation in MM.1S multiple myeloma cell line with IC50 10.1 nM. In the MM.1S multiple myeloma CB-17 CDX model, TQB3602 showed antitumor efficacy with TGI > 100% @7 mpk, BIW (tumor can’t be measured from day 17). Conclusions: We have identified a novel potent proteasome inhibitor TQB3602. Preclinical studies showed antitumor efficacy of TQB3602 in MM.1S multiple myeloma model. TQB3602 represents a promising clinical candidate for treating multiple myeloma and the First-in-human trial is expected in the middle of 2020.
Efficacy and tolerability of elotuzumab-based three-drug regimens for high-risk multiple myeloma: A meta-analysis.
Authors: Farooqui Arafat Ali , Nabeel Shaha , Tariq Muhammad , Ashraf Aqsa , Ahmed Zahoor , Faisal Muhammad Salman , Ammad Ud Din Mohammad , Shahab Zartashia , Setarehaseman Alireza , Anwer Faiz 
Published: May 2020

e20550 Background: Efficacy of elotuzumab (E) based regimens in high risk multiple myeloma (MM) (i.e, ISS stage II/III and t(4;14) or (del17p) has not been thoroughly investigated. The aim of this study was to assess the efficacy of E based 3-drug regimens compared to non-E based regimens in high risk MM. Methods: A systematic review of literature was done to identify randomized controlled trials (RCTs) which reported overall response rates (ORR), progression free survival (PFS) and overall survival (OS) of MM patients (pts) with E based 3-drug regimens. Odds ratios (OR) of ORR were computed and hazard ratios (HR) of PFS and OS (along with 95% confidence intervals; CI) were extracted to compute a pooled HR using RevMan v.5.3 to report the efficacy of E based 3-drug regimens. A random effects model was employed only when there was significant heterogeneity among studies ( > 40%, as assessed by I-squared). Results: After screening 604 studies, 04 RCTs were included (n = 986 patients). E was evaluated with lenalidomide (L), pomalidomide (P), bortezomib (B) and dexamethasone (d). ELd regimen was studied in 359, EPd in 60 and EBd in 77 pts. Total 496 pts were evaluated with E. Pooled analysis of E based 3-drug regimens showed improved PFS (HR 0.69, 95% CI 0.59-0.81; p < 0.00001, I2 = 0%) and ORR (OR 1.92, 95% CI 1.33-2.78; p = 0.0005; I2 = 25%) as compared to non-E 2-drug regimens. Relapsed/refractory MM pts (n = 456) also showed improved ORR in E vs non-E groups (OR 1.88, 95% CI 1.19-2.97; p = 0.007; I2 = 47%). Sub-group analysis showed 30% reduction in progression in high risk MM pts (HR 0.70, 95% CI 0.53-0.94; p = 0.02; I2 = 0%) and 31% in standard risk pts (HR 0.69, 95% CI 0.53-0.88; p = 0.003, I2 = 0%). OS showed 25% reduction in risk of death with E based regimens (HR 0.75, 95% CI 0.62-0.91; p = 0.004, I2 = 0%). E proved to be clinically safe across all patients (OR 1.10, 95% CI 0.78-1.57; p = 0.58; I2 = 71%). Conclusions: Elotuzumab based 3-drug regimens appear to abrogate high risk features in MM compared to 2 drug regimens.
Mortality of multiple myeloma diagnosed peri-hospitalization.
Authors: Rubinstein Sam , Sigworth Elizabeth , Chaugai Sandip , Chen Qingxia M , Cornell Robert F. , Warner Jeremy Lyle 
Published: May 2020

e20553 Background: Although modern therapeutics for multiple myeloma (MM) have resulted in improved overall survival (OS) in recent years, patients who present with an acute disease-related complication often have poor outcomes. We sought to compare the OS of patients diagnosed with MM in or shortly after hospitalization with those diagnosed in the outpatient setting. Methods: Patients treated for MM at Vanderbilt University Medical Center (VUMC) between 2000 and 2018 were included. OS was computed from date of diagnosis; patients still alive were censored at date last known alive or of last follow-up. Baseline laboratory and cytogenetic data were used to calculate Revised International Staging System (R-ISS) stage; age was also recorded. Dates of inpatient notes and encounter codes were identified and compared to date of diagnosis to identify patients diagnosed within 30 days of an inpatient stay; patients whose first encounter at VUMC was 30 days or more after their diagnosis date were excluded. Cox proportional hazards modeling was performed to investigate the effects of a diagnosis within 30 days of an inpatient encounter controlling for age and R-ISS on OS. Time-dependent coefficients were included to investigate the effects of a peri-hospitalization diagnosis on OS before and after 90 days. Mortality at 90 days for each group was compared using Fisher’s exact test. Results: A total of 681 patients were included, of whom 81 (11.8%) were diagnosed peri-hospitalization. Patients diagnosed peri-hospitalization had inferior OS within the first 90 days (adjusted HR 8.38, 95% CI 4.22-16.66, p < .001), but not after 90 days (Table). 90-day mortality for patients diagnosed peri-hospitalization was higher than for those not diagnosed peri-hospitalization (21.0% v. 3.3%, p < 0.001). Conclusions: Patients diagnosed with MM peri-hospitalization had high early mortality in this study, although patients surviving more than 90 days have similar mortality to those diagnosed as outpatients. Many factors could account for this finding, such as irreversible renal failure or immobility due to MM, hospital-related complications, or more aggressive MM phenotype. Predictive models of early mortality in MM should account for inpatient status at diagnosis. [Table: see text]
Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM).
Authors: Tam Eric Leon , Iberri David Joseph , Liedtke Michaela , Muffly Lori S. , Shiraz Parveen , Frank Matthew Joshua , Lowsky Robert , Rezvani Andrew , Negrin Robert , Meyer Everett , Arai Sally , Johnston Laura J. , Shizuru Judith , Weng Wen-Kai , Miklos David Bernard , Sidana Surbhi 
Published: May 2020

e20557 Background: The ideal choice of maintenance therapy in patients with HRMM high-risk multiple myeloma remains unknown. We analyzed the outcomes of patients with HRMM undergoing transplant receiving different maintenance approaches. Methods: Patients with MM undergoing their first ASCT from 2012-19 within 1 year of diagnosis were identified from the prospectively maintained database of patients undergoing ASCT. HRMM was defined as having t(4;14), t(14;16), t(14;20), del17p13, or gain 1q detected on fluorescent in situ hybridization (FISH). Results: Of the 412 patients undergoing ASCT within 1 year of diagnosis, 333 had FISH data available and of these, 37% (124/333) patients had high-risk cytogenetics. Distribution of HR cytogenetics was as follows: deletion 17p: 37% (n = 46), t(4;14): 27% (n = 34), t(14;16) or t(14;20): 12% (n = 26), gain1q: 31% (n = 41). 9% (n = 12) had more than one HR abnormality. In patients with HRMM, median age at transplant was 59 years (range: 39 to 73), and 61% (n = 103) were males. 64% (n = 107) of high-risk patients received post-transplant maintenance therapy. Maintenance therapy in this group included a proteasome inhibitor (PI) in 34% (n = 29), immunomodulatory drug (IMiD) in 59% (n = 51), or both in 7% (n = 6). There was no difference in baseline characteristics of HRMM patients receiving PI vs. IMiD maintenance, except that patients with del17p were more likely to receive PI maintenance therapy (55% vs 28%, p = 0.01). (Table) After a median follow-up of 3.1 years from diagnosis, patients with HRMM had inferior PFS compared to patients with standard risk disease, with median PFS of 3 vs. 4.8 years, p < 0.001. Amongst the 86 HRMM patients receiving maintenance therapy, median PFS in patients receiving PI vs. IMiD vs. both PI + IMiD maintenance was 3 vs. 3.2 vs. 2.2 years, respectively, log-rank p = 0.7. In the sub-group of patients with 17p deletion, median PFS in the three groups was 3 vs. 2.9 vs. 2.2 years, respectively, log-rank p = 0.7. Conclusions: Patients with HRMM have inferior PFS compared to patients with standard risk disease. We observed similar outcomes in HRMM patients post-transplant regardless of the choice of maintenance therapy. [Table: see text]
Use of treatment pathways reduce cost and increase entry into clinical trials in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Weese James L. , Shamah Corey J. , Sanchez Federico Augusto , Singh Maharaj , Huibregtse Carol , Clement Kevin , Barry-Weers Anne Marie , Bock Amy L. , Mitchell Dorothy L. , Beres Amy 
Published: May 2020

e21000 Background: VIA Oncology evidence-based pathways have been integrated into our medical oncology workflows since November 2014. Within 3 months, compliance was high for our 42 medical oncologists at 19 sites working with a common EHR with over 85% of pts treated on pathway. The aim of this study was to determine if there was a significant difference in the overall cost of treatment between pts treated on pathway versus off pathway, and whether on pathway pts had a lower rate of ED use and unplanned admissions within 30 days of chemotherapy as required in the new CMS directives. Methods: Newly diagnosed NSCLC pts diagnosed between January 1, 2017 to December 31, 2018 were identified from the tumor registry for the system. The VIA database was queried to separate these pts into two groups – those pts who were treated on pathway, and those who were off pathway. In addition, we divided pts into early diagnosis, advanced/curative, and advanced/non-curative. The data warehouse was utilized to determine the total charges of adjuvant medical oncology treatment for these pts. In addition, data was extracted for the same groups to determine those pts who sought ED evaluation and or hospital admission within 30 days of chemotherapy treatment (CMS-35). Statistical analysis was performed using Chi-square/Fisher’s exact test to compare proportions and t-test for independent samples to compare treatment costs and ED/hospitalizations between the on and off pathway groups. Results: During the 2 years, 407 (81.4%) NSCLC pts were treated on pathway (including clinical trials); 93 (18.6%) were off pathway. All patients undergoing treatment were ECOG 0-2 Performance Status. Mean cost for treating the on-pathway group was $104,436 compared to $183,717 for the off-pathway pts (p = 0.01). Since implementing pathways, clinical trial entry rose from 27 to 66/yr. 25.8% of on pathway compared to 29% of off pathway fell into the CMS 35 group. Conclusions: Standardized usage of evidence-based pathways can be used successfully across a large number of providers over wide geography. Adherence to pathways results in significant cost savings for each patient and significant rise in clinical trial entry.