bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pitfalls with analyses of real-world data: A look at ASCO’s CancerLinQ Discovery Multiple Myeloma dataset.
Authors: Shou Karen J , Thornton Jennifer A , Sunderland Kevin , DeStefano Christin 
Published: June 2023

e20033 Background: Real world data (RWD) are increasingly used in oncology research. Yet, a big limitation of RWD is missing data, potentially generating misleading conclusions. Methods for handling missing data include excluding patients with missing variables, using machine-based or statistically-imputed values, or using proxies (surrogates). Another limitation deals with excluding deaths at time zero, which may lead to misleading conclusions when analyzing survival of patients with aggressive cancers. This work highlights the impacts data exclusion, variable surrogacy, and death at time zero have on survival analysis results. Methods: ASCO’s CancerLinQ Discovery Multiple Myeloma (MM) dataset was used to assess overall survival (OS) in patients with MM diagnosed from 2009-2021. Of the 34,234 patients included in the actual analyses, 3,582 (10%) were missing a recorded date of MM diagnosis. In these cases, dates of first anti-myeloma therapy were used as surrogates since most MMs are treated at diagnosis. OS was compared between MM patients with “known” vs. surrogate or “presumed” diagnosis dates. To assess how the inclusion of deaths at time zero may or may not affect OS, the data were first analyzed by excluding patients who died within 1 month of second primary malignancy (SPM) diagnosis, including secondary AML (sAML). A second analysis of the same sample added a constant (0.5) to all survival times, allowing for inclusion of patients who died within one month of diagnosis. Analyses were conducted with STATA Version 17.0 (College Station, TX). Results: Despite the strong, positive correlation between recorded MM diagnosis date and date of first anti-myeloma therapy, there was a statistically significant difference in survival of MM patients with a known vs. presumed date of diagnosis (median OS 115 vs. 45 months, HR 2.54, 95% CI 2.41-2.69, p < 0.001). Dropping vs. including deaths within one month of diagnosis resulted in a marked difference (i.e., nearly 1 year) in median OS from the date of diagnosis of any SPM (113 vs. 103.5 months) as well as sAML (41 vs. 30.5 months). Conclusions: Although RWD hold promise, oncologists must be aware of common pitfalls in survival analyses: missing data, variable surrogates, and deaths at time zero being dropped. Patients with a recorded date of MM diagnosis appear to be fundamentally different from those who don’t have a date of diagnosis but do have a date of anti-myeloma therapy recorded. For aggressive malignancies, excluding patients who died at time zero can lead to over-estimation of survival. Adding a small constant (0.5) to the time variable can enable the inclusion of patients who die quickly after their cancer diagnosis. In conclusion, when utilizing RWD to guide clinical decision making, it is important to be aware of common threats to data validity, which can produce misleading results.
Health-related quality of life among patients with multiple myeloma treated with CAR-T therapy.
Authors: Gagnon Samantha Jane , Nooka Ajay K. 
Published: June 2023

e20040 Background: The regulatory approvals in myeloma were predominantly based on the safety and efficacy of the antimyeloma therapies. Health-related quality of life (HRQOL) metrics have not routinely been incorporated into these studies, nor were they a requirement for approval, which explains the dearth of HRQOL studies in myeloma. Recent approvals of chimeric antigen receptor T-cell (CAR-T) therapy targeting the B-cell maturation antigen were no different. While improved clinical outcomes in myeloma led to the FDA and EMA approvals, the CAR-T effects on HRQOL are not well described. Methods: We conducted a cross-sectional observational pilot study to evaluate HRQOL among patients that received CAR-T. Inclusion criteria were age >/= 18 years with a diagnosis of myeloma, had been treated with an autologous CAR-T a minimum of 56 days prior to survey date and had not yet experienced progression as defined by the IMWG criteria. HRQOL measurements were obtained using validated tool, self-administered FACT-MM questionnaire post-CAR-T infusion. The primary endpoint measurement was the FACT-MM composite score. Associations between FACT-MM scores and predictors were analyzed using nonparametric tests. FACT-MM and subscores were analyzed as continuous and dichotomous outcomes. Results: Between December 2021 and July 2022, 22 patients were enrolled (male: 54.55%, white: 54.55%). The median age of patients was 64 (range, 43-86) and the median time to enroll on the study from diagnosis is 6.5 years (3.5-17). Median FACT-MM score was 137.5 (IQR: 18.5) out of a maximum possible score of 164. The median trial outcome index (TOI) which is the sum of the physical and functional well-being (PWB and FWB), a predictor for physical and functional outcomes from treatment (FACIT) was 95 (IQR: 17) out of maximum possible 112. Other descriptive variables of interest were shown in the table. Differences in TOI were found between races (White, African American (AA), & Asian p = 0.04). In our sample, AA and Asian subjects had higher median TOI, therefore race should not be considered to have a negative impact on clinical trial success. Subjects with a history of Gilbert’s syndrome (2 vs 20), reported higher overall FACT-MM scores (p = p=0.04), PWB (p=0.03) and pain-related HRQOL (p = 0.04). Interestingly, we did not find that HRQOL differed by patients that had evidence of CRS or ICANS during CAR-T therapy, or by age, R-ISS, CCI, presence of EMD or prior lines of therapy (LOT). Conclusions: Patients treated with CAR-T have reported high HRQOL metrics at least 2 months out from infusion. Age, RISS, CCI, prior LOT did not impact the HRQOL and may not be the sole criteria used for decision making whether or not to offer CAR-T. [Table: see text]
Non-vitamin k oral antagonists versus aspirin for primary thromboprophylaxis in patients with multiple myeloma on outpatient chemotherapy: A systematic review and meta-analysis.
Authors: Costa Thomaz Alexandre , Costa Bruno Almeida , Felix Nicole , Godoi Amanda , Nogueira Alleh , Richter Joshua Ryan , Rossi Adriana 
Published: June 2023

e20041 Background: Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased in patients receiving immunomodulatory drugs (IMiDs). Current guidelines suggest that non-vitamin K oral anticoagulants (NOACs) may be an alternative to low-dose aspirin (ASA) for primary thromboprophylaxis in this population. However, there is limited data comparing these two antithrombotic therapies among MM patients undergoing treatment with IMiDs. Methods: We performed a systematic review and meta-analysis to compare NOACs with ASA for primary thromboprophylaxis in individuals with newly-diagnosed or relapsed/refractory MM undergoing outpatient chemotherapy with an IMiD-based regimen. PubMed, Cochrane, and EMBASE were systematically searched from inception to January 2023. Observational studies and randomized controlled trials were included when comparing NOACs versus aspirin for thrombotic and hemorrhagic outcomes. Statistical analysis was performed with Review Manager 5.4.1. Results: We included 10 randomized controlled trials and observational studies comprising 1026 MM patients who underwent primary thromboprophylaxis with NOACs (33%) or ASA (67%). Thromboprophylaxis with NOACs was associated with a significantly lower incidence of VTE compared with ASA (OR, 0.33; 95% CI, 0.16-0.68; p < 0.001; I² = 0%). Each group had one major bleeding event, with no statistically significant difference between NOACs and ASA (OR, 1.35; 95% CI, 0.05-35.51; p = 0.86; I² = 51%). Similarly, clinically relevant non-major bleeding (OR, 0.56; 95% CI, 0.12-2.70; p = 0.47; I² = 0%) and minor bleeding (OR 1.48; 95% CI: 0.42-5.24; p = 0.54; I² = 0%) event rates did not differ significantly between groups. Conclusions: These findings suggest that NOACs may be superior to ASA for VTE prophylaxis among MM patients receiving IMiD-based chemotherapy, with no significant difference in the overall bleeding risk between the two groups.
A phase IIb study of selinexor in combination with carfilzomib, daratumumab, or pomalidomide in patients with multiple myeloma relapsing on current therapy.
Authors: Biran Noa , Vesole David H. , Parmar Harsh V. , Phull Pooja , Doucette Kimberley , Feinman Rena , Zenreich Joshua , Anand Palka , Ivanovski Kristin , Pace Monique , Breeze Genevieve , Amer Rania , Biamonte Lisa , Aleman Adolfo , Unawane Rashmi , Pendergrass Elizabeth , Della Pia Alexandra , Kumka Susan , Siegel David Samuel DiCapua 
Published: June 2023

e20042 Background: Selinexor is an oral, selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1), leading to retention of tumor suppressor proteins and apoptosis in malignant cells. Preclinical studies suggest synergistic activity when selinexor is combined with other treatments for MM. We hypothesize the addition of selinexor can recapture response to patients relapsing or refractory on carfilzomib (CFZ), pomalidomide (POM) or daratumumab (DARA)-based regimens. Methods: This is an ongoing phase IIb, open-label, multicenter study to evaluate the safety and efficacy of selinexor plus CFZ, POM, or DARA in patients with MM. Patients were enrolled to each arm only if their disease was refractory to the specific drug of interest (CFZ for Arm 1, POM for Arm 2, and DARA for Arm 3). Arm 1 (n=1) consists of selinexor 80 mg orally on D1, 8, 15; CFZ 56 mg/m2 IV on D1, 8, 15; and dexamethasone (DEX) on D1, 8, 15, 22. Arm 2 (n=7) consists of selinexor 60 mg orally on D1, 8, 15; POM 4 mg orally on D1-21; and DEX on D1, 8, 15, 22. Arm 3 (n=7) consists of selinexor 100 mg orally on D1, 8, 15, 22; DARA 16 mg/kg IV or 1,800 mg SQ on D1, 8, 15, 22 for C1-2; D1 and 15 for C3-6; D1 for ≥C7; and DEX on D1, 8, 15, 22. The primary endpoint is ORR and secondary endpoints include PFS, OS, MRD negativity and TEAEs. Results: At data cutoff (Feb 6 2023), 15 patients were enrolled with a median age of 64 years (range 60-83), 27% with ISS stage III MM, 73% with high-risk cytogenetics, 93% refractory to the last LOT, 47% triple refractory, and 33% quadruple refractory (Table). The ORR was 33% (4/12; 4 PR) and the CBR was 92% (11/12; 7 SD); 3 patients are pending. The most common grade 3-4 TEAEs (n=34) were neutropenia (32%), hypophosphatemia (9%), pneumonia (6%), hyperglycemia (6%), and fatigue (6%). Ten patients discontinued treatment due to PD (n=5), withdrawal of consent (n=2), or TEAEs (n=3; fall, diarrhea, and RSV pneumonia), of whom 1 patient died while hospitalized for diarrhea and weakness. Conclusions: Preliminary results show selinexor plus CFZ, POM, or DARA is safe and restores sensitivity to therapy in relapsed/refractory MM patients. In this population of heavily pretreated MM patients, the ORR (33%) and CBR (92%) observed are higher compared to those seen with single-agent selinexor (ORR 4% and CBR 21%) (Chen C et al, Blood 2018). Clinical trial information: NCT04661137 . [Table: see text]
Efficacy of teclistamab in patients (pts) with heavily pretreated, relapsed/refractory multiple myeloma (RRMM), including those refractory to penta RRMM and BCMA (B-cell maturation antigen) directed therapy (BDT).
Authors: Venkatesh Priyanka , Atrash Shebli , Paul Barry , Alkharabsheh Omar , Afrough Aimaz , Mahmoudjafari Zahra , Mushtaq Muhammad Umair , Hashmi Hamza , Davis James A. , Abdallah Al-Ola A. 
Published: June 2023

e20044 Background: Teclistamab is a B-cell maturation antigen (BCMA) targeting bispecific agent approved in 10/2022 for pts with relapsed refractory multiple myeloma (RRMM) based on the results of the MAJESTEC-1 study. This is the first report on the real-world safety and efficacy of teclistamab in pts with RRMM and highlights patterns of utilization and outcomes in pts, including those who would have been ineligible for enrollment on MAJESTEC-1. Methods: Twenty-two pts with RRMM who received teclistamab at the University of Kansas Health System as of 2/10/2023 had electronic medical records (EMR) reviewed retrospectively in collaboration with US Myeloma Innovations Research Collaborative (USMIRC). Baseline pt characteristics were outlined by descriptive analyses. Responses were evaluated using the International Myeloma Working group (IMWG) criteria. Adverse events were graded based on the CTCAE v5.0 criteria. Results: Pts included in the analysis had received a median of 6 prior LOT and 64% had extramedullary disease (EMD). All of the pts were triple class exposed and 91% were triple class refractory, 77%/59% were penta-class exposed/refractory, while 72% were refractory to prior BCMA directed therapy (BDT). Median follow up was 3.1 (1.7-4.1) months. The most common grade III/IV hematological toxicities were lymphopenia (95%), neutropenia (36%), leukopenia (36%), thrombocytopenia (32%) and anemia (9%). Cytokine release syndrome (CRS) was observed in 9 (41%) pts, all o which were grade I/II events, while immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 5 (23%) pts, with 2 (9%) pts having grade III events. The overall response rate was 50%, and was 56%,46% and 28% for pts who were BDT refractory, penta- refractory, or had EMD, respectively. Of those that did respond, responses tended to be deep (73% ≥ VGPR; 55% ≥ CR). No treatment related mortality was observed, although5 (23%) pts died due to disease progression during follow up. Conclusions: Our study demonstrates the efficacy of teclistamab in heavily pre-treated RRMM, including those who were penta-refractory, BDT refractory, or had EMD. Overall, teclistamab was well tolerated with no major safety events. Keywords: Plasma cell disorders, relapsed multiple myeloma, Penta-class refractory myeloma, BCMA directed therapy. [Table: see text]
Belantamab mafodotin (belamaf) for relapsed/refractory multiple myeloma (RRMM): A real-world observational study update.
Authors: Hultcrantz Malin , Kleinman David , Vij Ravi , Escalante Fernando , Delforge Michel , Kotowsky Nirali , Bitetti Jacopo , Boytsov Natalie , Camadoo-O'Byrne Leena , Powers Happ Lindsey , Rohman Mujib , Germain Guillaume , Duh Mei Sheng , Laliberté François , Mahendran Malena , Urosevic Ana , Lee Hans C. 
Published: June 2023

e20046 Background: A prior retrospective analysis of US patients (pts) with RRMM suggested that pts treated with belamaf, a BCMA-targeting antibody-drug conjugate, experienced similar outcomes to those who received belamaf in the pivotal DREAMM-2 study. This updated analysis aimed to characterize pts, assess occurrence and management of ocular adverse events (AEs), and evaluate belamaf effectiveness in a real-world setting. Methods: This retrospective, longitudinal, observational study used data sourced from the US EHR-derived Flatiron Health de-identified database (01/01/2011–06/30/2022). Eligible pts had a confirmed MM diagnosis, initiated belamaf after FDA approval (08/05/2020; first administration=index date), were ≥18 years old at index, and had chart abstraction data for ocular safety and treatment effectiveness. Data on ocular AEs were reported separately for all pts and pts with ≥4 months (mo) of follow-up to allow for sufficient follow-up to evaluate incidence of ocular AEs and their mitigations. Tumor response was assessed in all pts, along with Kaplan-Meier estimates of duration of response (DoR), overall survival (OS), and progression-free survival (PFS). Results: Of the 184 pts included in the study, mean age was 68.7 years; 64% were White and 47% were female. Eastern Cooperative Oncology Group (ECOG) status was ≥2 in 28% patients, 62% had received ≥5 prior lines of therapy, and 82% were triple-class refractory. Median (IQR) follow-up was 4.1 (1.9–8.5) mo. Among pts with ≥4 months of follow-up (n=94) 75% had ≥1 ocular AE, with keratopathy and blurred vision being the most frequent. Mean (SD) time to first ocular AE was 39 (34) days. Most ocular AEs were managed by therapy hold (69%; of which 73% restarted belamaf) and/or AE treatment (63%). The median dose hold due to ocular AEs was 43 days (physician-reported keratopathy: mild, 21 days; moderate/severe, 56 days). In all pts, 39 (21%) had a derived tumor response based on serum free light chain levels, (partial response: 74%, very good partial response: 51%). For all pts, the estimated median DoR was 9.1 mo, PFS 4.5 mo, and OS 7.9 mo, while the 6-month DoR rate was 57%, PFS rate was 46%, and OS rate was 58%. Conclusions: Overall, belamaf was effective in the real world setting in heavily pre-treated pts with RRMM and limited therapy options. The AE profile was consistent with DREAMM-2. Ocular AEs were manageable and despite their occurrence, a high percentage of pts remained on treatment, suggesting belamaf may fill an unmet need for triple-class refractory pts with RRMM. [Table: see text]
Sequencing bispecific antibodies and CAR T cell therapy in multiple myeloma with prior exposure to BCMA-targeted therapies.
Authors: Patel Urvi , Oluwole Olalekan O. , Kassim Adetola , Jayani Reena , Belliveau Paul , Savani Bipin , Dholaria Bhagirathbhai R. 
Published: June 2023

e20049 Background: In patients with heavily pretreated relapse and refractory multiple myeloma (MM), novel approaches such as immunotherapies and B-cell maturation antigen (BCMA) targeted therapies have been utilized to show favorable responses Despite these therapies however, patients continue to have disease progression leaving them with fewer options. A need exists to investigate the optimal sequencing strategies in the treatment approach for MM with novel bispecific antibodies (BsAbs) and CAR T cell therapy in patients previously exposed to BCMA-directed therapies. Methods: A comprehensive review of active clinical trials, published primary literature, and meeting abstracts was performed to gather efficacy endpoints and overall response rates (ORR) in patients receiving BsAbs or CAR T therapy with previous exposure to BCMA directed therapy. Results: A variety of BCMA and non-BCMA directed BsAbs along with CAR T cell therapy have been evaluated for ORR in patients who received previous BCMA-targeted therapies. Teclistamab, a BCMA BsAb induced an adequate response of 40% in patients who received previous BCMA directed antibody drug conjugate (ADC) or CAR-T- cell therapy, with a deepening of response observed in 28%. Elranatamab, an investigational BCMA-targeted BsAb demonstrated a preliminary ORR of 54% in a cohort of 13 pts. Talquetamab, a first in class GPRC5D BsAb induced an ORR of 50% in pts with previous BCMA-directed therapy as monotherapy and resulted in an ORR of 72% in combination with daratumumab. Cevostamab, an investigational FcRH5 directed BsAb demonstrated an adequate ORR of 47% in 20 pts who received previous BCMA-directed therapy. In parallel to evaluating responses for BsAbs, CAR T cell therapies including cilta-cel and ida-cel have also induced favorable and durable responses in their prior BCMA therapy exposed cohorts with an ORR of 60.0% and 74% respectively. Comparable safety profiles across both BCMA treatment exposed and BCMA treatment-naive cohorts were observed among all studies. Additional endpoints including minimal residual disease and incidence of infections are to be included in final results. Conclusions: This analysis indicates that sequencing BsAbs and CAR -T cell therapy after previous BCMA-targeted treatments offers meaningful clinical benefit with durable response rates in patients who have few other options. Longer follow up and larger studies are needed to further evaluate their enhanced benefit and generate greater insight for optimal sequencing strategies in heavily pretreated MM patients who have exhausted other options. [Table: see text]
Bendamustine-bortezomib-dexamethasone in relapsed/refractory multiple myeloma.
Authors: Cerchione Claudio , Nappi Davide , Cangini Delia , Ronconi Sonia , Ceccolini Michela , Musuraca Gerardo , Martinelli Giovanni 
Published: June 2023

e20051 Background: Bendamustine is an old bi-functional alkylating agent which has proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Thus, aiming to provide further insights in this field, also in novel agents’era, we present here a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD). Methods: 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. Setting and Patients: All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. Results: Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of Bendamustine was 9.6 months (r.2-36). Conclusions: BVD has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to SCT, also after failure of novel agents. Clinical trial information: FEDII 2022000378 .