bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pomalidomide, bortezomib, and dexamethasone in lenalidomide-pretreated multiple myeloma: A subanalysis of OPTIMISMM by frailty.
Authors: Oriol Rocafiguera Albert , Dimopoulos Meletios A. , Schjesvold Fredrik , Beksac Meral , Yagci Münci , Larocca Alessandra , Guo Shien , Mu Yutian , Hong Kevin , Dhanasiri Sujith , Richardson Paul G. , Weisel Katja 
Published: June 2022

8024 Background: Patients (pts) with multiple myeloma (MM) are likely to be older adults, and advanced age is associated with lower survival rates, in part due to comorbidities and frailty. Results from the phase 3 OPTIMISMM trial (NCT01734928) demonstrated that pomalidomide (P) in combination with bortezomib + dexamethasone (Vd) significantly improved progression-free survival (PFS) in lenalidomide (LEN)-pretreated pts with relapsed/refractory MM (RRMM) vs Vd, irrespective of age and Eastern Cooperative Oncology Group performance status (ECOG PS). Here, we report results from a post hoc analysis assessing outcomes of PVd vs Vd in pts with RRMM by frailty status. Methods: Pts with MM and 1–3 prior lines of therapy (including a LEN-containing regimen) who had been randomized 1:1 to PVd or Vd were assessed for frailty. Frailty scores were calculated using age (≤ 75 yr = 0; 76–80 yr = 1; > 80 yr = 2), the Charlson Comorbidity Index (≤ 1 = 0; > 1 = 1) and ECOG PS (0 = 0; 1 = 1; ≥ 2 = 2). Pts were classified as non-frail (NF; combined score: 0 or 1) or frail (F; combined score: ≥ 2). PFS, overall response rate (ORR), and safety outcomes were assessed by treatment group and frailty status. Results: In the intent-to-treat population (N = 559) (data cutoff Oct 26, 2017), 93/281 (33.1%) pts who received PVd and 93/278 (33.5%) who received Vd were frail. Baseline characteristics were similar between treatment groups within each frailty subgroup. Median PFS was longer with PVd vs Vd in NF ( P = 0.001) and F ( P = 0.006) subgroups (Table). ORR was higher with PVd vs Vd in NF ( P < 0.001) and F ( P < 0.001) subgroups. Incidence of grade ≥ 3 (G3) treatment-emergent adverse events (TEAEs) was higher with PVd vs Vd in NF (88.1 vs 61.3%) and F (96.8 vs 87.9%) subgroups; peripheral neuropathy, acute renal failure, and hypertension were the most common. Treatment discontinuation due to G3 TEAEs was greater with PVd vs Vd in NF (19.2 vs 18.5%) and F (30.1 vs 20.9%) subgroups. PVd had a longer median treatment duration vs Vd in NF (8.8 vs 5.7 mo) and F (8.9 vs 4.3 mo) subgroups. Conclusions: Frail pts with RRMM who received PVd had longer PFS and higher ORR than pts who received Vd, consistent with the overall OPTIMISMM results. Frail pts experienced more G3 TEAEs and treatment discontinuations with PVd vs Vd, but treatment duration was longer with PVd vs Vd. Clinical trial information: NCT01734928. [Table: see text]
Characteristics of long-surviving patients with multiple myeloma: Over 12 years of follow-up in the Connect MM Registry.
Authors: Terebelo Howard R. , Omel James , Wagner Lynne I. , Hardin James W. , Rifkin Robert M. , Ailawadhi Sikander , Durie Brian G. , Narang Mohit , Toomey Kathleen , Gasparetto Cristina J. , Joshi Prashant Ramesh , Yu Edward , Flick E. Dawn , Chung Weiyuan , Lee Hans C. , Abonour Rafat , Jagannath Sundar 
Published: June 2022

8027 Background: The Connect MM Registry is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed multiple myeloma (NDMM) and one of the largest, longest running MM registries. Long-term survivors (LTS), defined as patients (pts) who have ≥ 8 years of follow-up, comprise a large portion of the Connect MM Registry. The purpose of this analysis was to assess LTS demographic and clinical characteristics. Methods: Adult pts with NDMM (N = 3011) were enrolled from 250 community, academic, and government sites: Cohort 1 from 2009 – 2011 and Cohort 2 from 2012 – 2016. As 99% of LTS were enrolled in Cohort 1, only pts from Cohort 1 were included in this analysis. Pt data were unevaluable if there were missing treatments, disease assessments, or large gaps in activity during follow-up (n = 28). Baseline characteristics, treatment patterns, and quality of life (QoL) form completion rates were examined. Results: At data cutoff (5/17/21), of the 1493 pts in Cohort 1 with evaluable data, 279 were LTS and 1186 were non-LTS. LTS were generally younger and had better performance status at enrollment (Table). Most (66%) LTS received stem cell transplants and few experienced progression within the first 6 months (3%). Top first-line (1L) regimen for LTS was lenalidomide/bortezomib/dexamethasone (31%) vs bortezomib/dexamethasone (22%) in non-LTS. At data cutoff, 73% of LTS were still on treatment at their most recent visit. LTS underwent disease assessments more frequently (2.0 vs 1.3 per year) and had a higher QoL completion rate by year 5 (58% vs 46%). This analysis showed an estimated 8-year survival of 36% vs an observed 8-year survival of 39% from the SEER database. Additional analyses are ongoing. Conclusions: LTS were younger and healthier than non-LTS. Most LTS received triplets at induction, stem cell transplants in 1L, and were less likely to relapse within the first 6 months of treatment than non-LTS. These findings are consistent with what has been observed in MM clinical trials. Further, this analysis demonstrates the value of longitudinal data in the CONNECT MM Registry and provides insights on long surviving pts with MM. Clinical trial information: NCT01081028. [Table: see text]
Circulating tumor DNA analysis and association with relapse in patients with primary refractory multiple myeloma receiving secondary salvage therapy.
Authors: Mithraprabhu Sridurga , Reynolds John , Turner Rose , Kalff Anna , Bergin Krystal , Quach Hang , Khong Tiffany , Durie Brian G. , Spencer Andrew 
Published: June 2022

8037 Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with a 5 year-median overall survival (OS) in newly diagnosed (ND) patients. Real-world data reveals that 23% of transplant eligible (TE) ND MM patients relapse within 12 months of starting first-line bortezomib (1LB) based therapy and of these ̃50% will fail secondary therapy and die within 18 months. It is currently impossible to identify these high-risk patients and genomic studies could potentially inform alternative secondary therapeutic options. We propose that circulating tumour DNA (ctDNA) analysis could provide a more holistic approach to determine genomics of high-risk patients than bone marrow (BM) tumour DNA analysis in this genetically heterogenous multi-site malignancy. Methods: Peripheral blood plasma and BM samples (n = 186) were obtained at baseline, cycle 3 day 1 (C3D1), end of the study (EOS) and/or relapse, whichever appeared earlier, from a Phase II multicentre single arm study of carfilzomib-thalidomide-dexamethasone (KTd) in 50 TE ND MM patients who were refractory or registered suboptimal response to 1LB (Australasian Leukaemia and Lymphoma Group - MM17 trial). Somatic variants were identified in BM or ctDNA with ultra-sensitive targeted amplicon sequencing of 22-genes known to be mutated in MM. Mutational spectrum was correlated to standard MM risk factors including International Staging System (ISS), response to 1LB and KTd, cytogenetics/FISH, lactate dehydrogenase (LDH) levels, progression-free survival (PFS) and OS. Results: Our initial analysis of ctDNA mutational proportions between patients who did not or did experience relapse on KTd revealed a significantly higher proportion of RAS/RAF (3% vs 25%), or ATM/ATR/TP53 (17% vs 41%; p < 0.0001), respectively, in relapse patients. Subsequently, we correlated ctDNA RAS/RAF and/or ATM/ATR/TP53 mutational presence to standard MM risk factors. We identified a shorter PFS and OS for ISS Stage 2 and 3 compared to Stage 1 patients (p = 0.002 and p = 0.02, respectively) and a significantly higher proportion of RAS/RAF or ATM/ATR/TP53 mutations in patients with refractory as compared to sub-optimal response to 1LB therapy (p = 0.0002). Patients with RAS/RAF or ATM/ATR/TP53 mutations in ctDNA at the time of starting salvage therapy also had a shorter PFS and OS on KTd (p = 0.003 and p = 0.02, respectively). Sequential ctDNA analysis discovered that in 87.5% of patients, one or more of the dominant mutations present at the time of relapse were already present at the start of salvage therapy. Conclusions: Our analysis reveals that RAS/RAF and ATM/ATR/TP53 mutations in ctDNA could be prognostic biomarkers of response to secondary salvage therapy in primary refractory patients thus providing the opportunity to design targeted salvage treatment paradigms in high-risk MM patients.
Prevalence of ocular comorbidities in patients with multiple myeloma: An analysis of U.S. claims data.
Authors: Ailawadhi Sikander , Ma Qiufei , Jalbert Jessica J. , Zhou Mo , Zhou Zheng-Yi , Downes Nathaniel , Briggs Allison , Chi Lei , Hampp Christian , Song Xue , Noguera-Troise Irene , Weyne Jonathan , Kroog Glenn Scott , Rodriguez-Lorenc Karen 
Published: June 2022

8038 Background: Multiple myeloma (MM) predominantly affects older patients (pts) (median age at diagnosis 69 yrs) in whom comorbidities must be considered to manage the disease appropriately. Some anti-MM therapies can be associated with ocular toxicities and require careful attention when used among pts with pre-existing ocular comorbidities (OC). In 2018, 41% of Medicare enrollees had OC. Despite the potential implication on treatment decisions, information on pre-existing OC (e.g., disorders of lens, glaucoma) in MM pts is limited. This study aims to describe the prevalence of OCs among real-world pts with MM in 2011-2020 in the US. Methods: Adults with newly diagnosed MM (NDMM) with or without treatment, with 1L systemic therapy, and with relapsed/refractory MM (RRMM) who received up to 4 lines of systemic therapies (LOT) for MM were identified in the IQVIA PharMetrics Plus data. The index date was the date of initial MM diagnosis or a LOT initiation date. The prevalence of OC in each group was defined as the presence of any OC ICD 9/10 diagnosis codes in the 12 months prior to the index date. OCs (e.g., disorders of conjunctiva, lens, choroid, retina, glaucoma) were considered a potentially MM-related disease manifestation or MM treatment-related toxicity based on published literature and clinical expert opinion. Results: The median age at initial MM diagnosis was 64 yrs overall (N=49,814), and 63 yrs among treated pts (N=22,963). The median age was 63 yrs at 1L initiation and 64 yrs at 2L, 3L, and 4L initiation. The prevalence of OC at initial MM diagnosis was 39.0% overall and 35.2% among treated pts (Table). The OC prevalence was 35.8% prior to 1L initiation and higher in RRMM pts (42.1%, 44.9%, and 45.7% prior to 2L, 3L, and 4L initiation, respectively). This trend was observed across all OC categories, among MM-related OCs, and across all age groups. The prevalence of OC by MM stage was stable over the years. Conclusions: Approximately 40% of NDMM pts have a pre-existing OC, and the prevalence increases with the number of LOT in RRMM. While some OC may be due to aging, the impact of OC on treatment decisions for MM should be explored. [Table: see text]
Idecabtagene vicleucel (Ide-cel) chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory multiple myeloma (RRMM): Real-world experience.
Authors: Hansen Doris K. , Sidana Surbhi , Peres Lauren , Shune Leyla , Sborov Douglas W. , Hashmi Hamza , Kocoglu Mehmet H. , Atrash Shebli , Simmons Gary , Kalariya Nilesh , Ferreri Christopher J. , Afrough Aimaz , Kansagra Ankit J. , Voorhees Peter M. , Alsina Melissa , McGuirk Joseph , Locke Frederick L. , Patel Krina K. 
Published: June 2022

8042 Background: Ide-cel, a BCMA directed CAR T-cell therapy, was FDA approved 3/26/2021 for the treatment of RRMM after 4 prior lines of therapy. We evaluated the real-world outcomes of patients treated with standard of care ide-cel under the commercial FDA label. Methods: Ten US academic centers contributed data to this effort independent of the manufacturer. As of 1/10/2022, 138 patients were leukapheresed with overall manufacturing failure in 6 (4%). 108 patients were infused ≥ 30 days prior to data-cut off and constitute the study population for this retrospective analysis. Results: Table describes the study population compared to the pivotal KarMMa-1 trial (Munshi et al, NEJM 2021). Patients in our study were less likely to have ECOG PS of 0/1 (77%) and more likely to be penta-refractory (41%). 67% of patients would not have met eligibility criteria for KarMMa. Common reasons for ineligibility (> 1 reason in 22% patients) were co-morbidities (28%), cytopenias (22%), prior therapy with alloSCT/CAR-T/other BCMA therapy (19%), CNS myeloma/non-measurable disease/plasma cell leukemia (13%), and fitness (12%). 81% of patients received bridging therapy. Toxicity was comparable to that seen in KarMMa-1. Cytokine release syndrome (CRS) was seen in 82% (> grade 3: 4%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 15% (> grade 3: 5%) of patients, respectively. Tocilizumab and steroids were used in 72% and 25% of patients, respectively. Infections were seen in 34% of patients. Day 30 response was evaluable in 104 patients. Response rates were: ≥ partial response, 83%; ≥ very good partial response, 64%; and ≥ complete response (CR), 34%. 11% of patients have died by data cut-off, 7 due to disease progression and 5 due to other causes (1 grade 5 CRS, 1 hemophagocytic lymphohistiocytosis, 1 progressive neurological weakness, 2 COVID-19). Conclusions: This multicenter retrospective study delineates the real-world outcomes of ide-cel CAR T-cell therapy for RRMM. Despite more patients being penta-refractory and less fit compared to the pivotal KarMMa trial, safety and 30-day responses in the real-world setting (overall response rate: 83%, CR: 34%) are comparable to the clinical trial population. Follow-up is ongoing and updated data will be presented. [Table: see text]
A patient perspective on cure in multiple myeloma: A survey of over 1,500 patients.
Authors: Mohyuddin Ghulam Rehman , Ahlstrom Jennifer M. , Chmielewski Cynthia , Sweeney Nathan W. , Molina Thomas H. , Cheung Christian S. , Ballard Emily Watabe , Seng Felicia , Godara Amandeep , McClune Brian , Sborov Douglas W. 
Published: June 2022

8046 Background: As treatments advance in multiple myeloma (MM) and increasingly deeper and longer responses are achieved, the definition of what a cure is becomes increasingly relevant. While many physicians quote that patients may achieve a “functional cure”, understanding the patient perspective on the concept of cure has yet to be explored. Methods: HealthTree Cure Hub by the HealthTree Foundation represents an online portal for patients with plasma cell dyscrasias to help navigate their disease. It is the largest single database of patients with multiple myeloma with over 10,200 patients as of January 2022. Using this platform, we surveyed patients online from November 11th 2021 to Feb 7th 2022. Varying scenarios incorporating toxicity, disease status, and being on/off treatment were presented, and participants were asked to rate them from 1-5, with 5 being an ideal cure. Patient awareness of the term functional or operational cure was also. Results: A total of 1525 participants completed the survey. Table lists characteristics of the patients who completed this survey. The majority of the patients were female (55.5%), college educated (88.5%) and non-Hispanic White (70.7%). Most patients rated being off treatment permanently and having no evidence of disease as a cure (1116/1469, 75.5%), with a median score of 5 amongst respondents, indicating an ideal version of cure. Continuing to take the same pill or injection with significant toxicity and no evidence of disease had a median score of 1, a score lower than either “continuing to take same pill or injection without significant toxicity even in the evidence of disease” (median score 2) or “stopping treatment permanently even with some detectable disease” (median score 2). The majority of patients (76.3%) reported being unfamiliar with the term functional or operational cure. Conclusions: In the first study of patients with plasma cell dyscrasias in which patients were asked about their perceptions of what a cure is, our results highlight that drug toxicity and being on treatment profoundly impacts patient's perception of cure. Furthermore, most patients are not familiar with the term functional or operational cure. Future efforts should recruit more diverse patient populations and incorporate patient preferences in approaches to defining cure in myeloma, as well as explaining cure in easily comprehensible terms to patients. [Table: see text]
COVID vaccine immune response in patients with plasma cell dyscrasia: A systematic review.
Authors: Faizan Unaiza , Nair Lakshmi G. , Evans James , Anwer Faiz 
Published: June 2022

8067 Background: The defective immune system in plasma cell dyscrasia places patients at a higher risk of developing a severe infection, which is one of the leading causes of death in such patients. In an era of a global pandemic, it is essential to protect them against COVID-19, but fewer effective plasma cells lead to a suboptimal response to vaccines. There is still a lack of evidence whether the seroconversion is truly clinically relevant and if patients with plasma cell disorders would benefit from frequent boosters to maintain antibody levels. Methods: Online databases including PubMed, CINAHL, Ovid, and Cochrane were searched (January 11th, 2022), following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Only articles published in the English language were included. Abstracts, case reports, and case series were excluded. Out of 40 studies, 5 articles were selected for a systematic review. Results: In all 5 studies (N=654), seroconversion post-vaccination was used as a positive response to COVID-19 vaccination. Although patients with plasma cell disorders had a lower seroconversion rate compared to controls, the overall percentage was substantial and ranged between 23-95.5%. Amongst patients on active therapy, lower seroconversion rates were seen in patients on a CD-38 inhibitor, ranging from 20.2-92.1% (N=174). Also, a significantly lower percentage was recorded in patients above 65 years and those who have been treated with multiple therapies previously. Better seroconversion rates were seen in mRNA vaccines compared to J&J. Conclusions: Variable seropositive rates are seen in patients with plasma cell dyscrasias, lower rates are reported in patients on active therapy, CD-38 targeting therapy, and elderly patients. Hence, these patients should receive a 4 shot series. [Table: see text]
Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for patients with stage III-N2M0 non-small cell lung cancer (NSCLC): A population-based study.
Authors: Akhdar Marah , Syaj Sebawe , Alser Osaid , Elshami Mohamedraed , Hamouri Shadi 
Published: June 2022

8503 Background: Stage III-N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease with controversial management options. Induction therapy as part of multimodal treatment is the standard of care for Stage III-N2 NSCLC. We aim to investigate the effect of adding radiotherapy to neoadjuvant chemotherapy on survival outcomes. Methods: All adult NSCLC patients diagnosed between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database using ICD-O-3 histologic type coding. Inclusion criteria involved stage III NSCLC patients with ipsilateral lymph node involvement (N2), of any T stage, and with no known distant metastasis (M0). Our main sub-cohorts were patients who either underwent chemoradiotherapy (CRT) or chemotherapy (CT) in neoadjuvant settings. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. Cox proportional hazards model was used to analyze the effect of each treatment modality on OS and CSS in univariate and multivariate fashions. Multivariate analysis was adjusted for age, sex, marital status, T stage, resected lymph node status, tumor histology, primary site, laterality, and surgical procedure. Inverse probability treatment weighting (IPTW) was applied to create weighted samples based on study covariates. Results: Our analysis included 1175 patients; 799 (68.0%) underwent neoadjuvant CRT and 376 (32.0%) underwent neoadjuvant CT. Sample median age was 63 (IQR:56-69) years. T2 stage was the most prevalent (N =561, 47.7%), followed by T4 (N=243, 20.7%), T1 (N=228, 19.4%), and T3 (N=143, 12.2%). The main tumor histology was non-squamous cell carcinoma in 773 (65.8%) patients. The upper lobe was the most common primary tumor site (N =788, 67.1%). Patients underwent lobectomy (N=917, 78.0%), pneumonectomy (N=184, 15.7%), or sub-lobar resection (N=69, 5.9%). Adding radiotherapy to chemotherapy showed a slightly higher median OS than chemotherapy alone in neoadjuvant settings (51 vs. 47 months, respectively), and a higher median CSS (75 vs. 59 months, respectively). However, these differences were not statistically significant for OS or CSS (HR = 1.08, 95% CI: 0.91-1.28 and HR = 1.04, 95% CI: 0.89-1.21, respectively). After adjustment, age, T3-T4 stage, non-squamous histology, lower lobe primary site, positive resected lymph nodes, and pneumonectomy were all significant independent predictors for worse OS and CSS. IPTW analysis showed no remarkable survival advantage for CRT patients (HR = 1.15, 95% CI: 0.95-1.40 and HR= 1.12, 95% CI: 0.90-1.39) for OS and CSS, respectively. Conclusions: Adding radiotherapy to neoadjuvant CT did not result in significant survival benefits. Multiple prognostic factors should be taken into consideration when identifying the optimal choice and sequence of multimodal treatment for stage III-N2M0 NSCLC patients.