bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating differential cost growth across individual cancers: Insights from Oncology Care Model data.
Authors: Chaudhry Basit Iqbal , Gordan Lucio N. , Yue Andrew , Tran Lisa , Connor Nora
Published: June 2021

e18853

Background: Analyzing cost growth in oncology often faces significant challenges, including fragmentation of data for infused vs. oral agents and ascertaining the cost of inpatient care. How differential cost growth at the individual cancer level contributes to aggregate cost growth in oncology is often opaque. We leverage the integrated claims data provided by Medicare for its Oncology Care Model (OCM) pilot to analyze variations across individual cancers with respect to cost growth. Methods: OCM’s innovative methodology creates a natural experiment where costs are compared against a counterfactual comprised of Medicare patients seen in non-OCM practices. Leveraging this differential counterfactual provides an opportunity to gain insight into cost growth for individual cancers compared to oncology as a whole. Specifically, cost growth is measured each Performance Period (PP) with respect to the Baseline Period, from 2012 to 2015. We analytically decomposed and remodeled key quantitative factors in OCM associated with cost dynamics in oncology, including the Trend Factor (TF), which represents non-OCM cost growth. From 124,896 episodes, we sampled with replacement 19,191 episodes from 17 practices between PP1 and PP6 using empirical data distributions. We assumed neutral novel therapy and experience adjustments and then compared the overall TF to the remodeled cancer-level TF, reaggregated from the individual episodes. Results: Reallocating the TF reveals that cost growth among cancer types is highly variable in the broader Medicare population. Cost growth at the individual cancer level varied from +99.3% to -14.3%. Of the 21 OCM cancers, 18 have TFs greater than zero, indicating cost growth in the non-OCM Medicare population since the Baseline Period. Four have a TF greater than 50%. Three cancer types show decreasing costs relative to the baseline period: intestinal cancer, MDS, and CNS tumor. Conclusions: Significant variation exists across individual cancer subtypes in terms of cost growth. Aggregate analyses of cancer at large have insufficient specificity to rationalize payment mechanisms. Payment reform efforts within cancer care should directly address dynamics at the individual cancer or cancer subtype level in order to provide more valid considerations for expected resource utilization, including in future payment policies. [Table: see text]
A population-based study of acute panmyelosis with myelofibrosis in the United States: 2004 to 2015.
Authors: McLaughlin Nicole , Ruan Gordon , Day Courtney N. , Harmsen William S. , Smith Caleb J. , Binder Moritz , Gangat Naseema , Go Ronald S. , Tefferi Ayalew , Shah Mithun Vinod
Published: June 2021

e19003

Background: Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid leukemia characterized by acute panmyeloid proliferation with increased blasts, cytopenias with bone marrow fibrosis, and absence of splenomegaly. There is a paucity of population-based studies of APMF. Methods: We queried the United States Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB) using the ICD-O-3 code 9931/3. The SEER 17 registries (2004-2015) were used to find data on incidence. For NCDB data, comorbid disease burden was calculated using the Charlson-Deyo Score (CDS). Hazard ratios (HR) with confidence intervals (CI) were calculated using a Cox proportional hazards model. Overall survival (OS) was estimated with the Kaplan-Meier method. Variables significant in univariable analysis were included in a multivariable analysis. Results: We identified 260 APMF patients using the SEER database. Incidence was 0.3 cases/million individuals and did not change significantly from 2004-2015. With a median follow up of 6.9 years (95% CI 6.1-7.8), the median OS was 2.3 years (95% CI 1.7-2.8). We identified 530 APMF patients using the NCDB. The median age at diagnosis was 67 years (range 22-90) and 311 (59%) were male. With a median follow up of 5.0 years (95% CI 3.0-7.6), the median OS was 2.3 years (95% CI: 0.8-6.5). OS was 69%, 31%, and 18% at 1-, 5-, and 10- years, respectively. Patients diagnosed in 2012-2015 had a significantly improved OS compared to those diagnosed in 2004-2007 (HR 0.65, 95% CI 0.49-0.85; p=0.002). 271 patients (53%) patients received chemotherapy. The OS for those that received chemotherapy was 70% at 1 year and 30% at 5 years versus 70% and 32% at 1- and 5- years for those who did not ( p=0.99). The median time to chemotherapy from time of diagnosis was 25 days (range 0-532 days). 52 patients (10%) underwent transplantation and the OS of those patients was 90% at 1 year and 45% at 5 years versus 67% and 29% at 1- and 5- years for those who did not (HR: 1.7 (95% CI: 1.2-2.6), p=0.006). In univariable analysis, factors predicting inferior OS were age ≥ 65 years old at diagnosis (HR 1.8, 95% CI 1.5-2.3; p<0.001), male sex (HR 1.5, 95% CI 1.2-1.8; p<0.001), CDS ≥ 1 (HR: 1.5 (95% CI: 1.2-2.0), p<0.001), government insurance (HR 1.8, 95% CI 1.4-2.3; p<0.001), diagnosis at a non-academic facility (HR 1.6, 95% CI 1.2-2.0, p<0.001), and not receiving a hematologic transplant (HR 1.7, 95% CI 1.2-2.6; p=0.006). Multivariable-adjusted analysis is shown in the Table. Conclusions: The overall incidence of APMF has not changed between 2004 and 2015, but OS for 2012-2015 was improved compared to 2004-2007. Age ≥ 65 years old, male sex, CDS ≥ 1, and diagnosis at a nonacademic facility predicted inferior OS. Multivariable-adjusted analysis.[Table: see text]
Code status transitions in patients with high-risk acute myeloid leukemia (AML).
Authors: Abrams Hannah Rebeccah , Nipp Ryan David , Traeger Lara , Lavoie Mitchell W. , Reynolds Matthew J. , LeBlanc Thomas William , El-Jawahri Areej
Published: June 2021

e19009

Background: Patients with high-risk AML often experience aggressive medical care at the end of life (EOL) such as hospitalization and intensive care unit (ICU) admission. Despite this, studies examining code status transitions in this population are lacking. Methods: We conducted a mixed methods study of 107 patients with high-risk AML enrolled in supportive care studies at Massachusetts General Hospital between 2014-2019. High-risk AML was defined as 1) new diagnosis > 60 years or 2) relapsed/refractory AML. Two physicians used consensus-driven medical record review to characterize code status transitions. Code statuses were coded as ‘full’ (confirmed or presumed), ‘restricted’ (i.e., do not resuscitate), or ‘comfort measures only’ (CMO); confirmations of presumed status were not coded as transitions. Results: At diagnosis of high-risk AML, 91.9% of patients were ‘full code’ (48.5% presumed, 43.4% confirmed) and 8.1% had restrictions on life-sustaining therapies. Overall, 55.1% (59/107) of patients experienced a code status transition, with a median of two transitions (range 1-4). Median time from first to last transition was 11 days (range 1-306) and from last transition to death was 1 day (range 0-11). Most of these transitions (79.6%; 48/59) were transitions to CMO near EOL. We identified three processes leading to code status transitions (Table): 1) pre-emptive conversations prior to any clinical change (15.3%; 9/59); 2) anticipatory conversations at the time of acute clinical deterioration (15%; 9/59); and 3) futility conversations after acute clinical deterioration, focused on withdrawing life-sustaining therapy (64.4%; 38/59). Only 55.9% (33/59) of patients participated in their last code status transition and 22.0% (13/59) of these transitions occurred in the ICU or Emergency Room. Conclusions: Most patients with high-risk AML had code status transitions at EOL, often following clinical deterioration that limited their ability to engage in EOL discussions. Interventions to promote earlier and more specific code status conversations are needed to improve patients’ ability to voice their EOL preferences.[Table: see text]
First-line treatment outcomes of CML patients in a real-world data setting in Lebanon.
Authors: Nasr Fadi , Yehia Intissar , El Khoury Reem , Diab Saada , Ghoche Ahmad , Nasr Lewis
Published: June 2021

e19031

Background: BCR–ABL-targeting tyrosine kinase inhibitors (TKIs) constitute the cornerstone of treatment of CML leading to a life expectancy that is currently very close to that of age matched individuals in the general population. The aim of the current study was to describe aspects of CML in a real world data setting in Lebanon including responses to first lines with a specific focus on the impact of first-line treatment with imatinib compared to that of the second-generation TKI, dasatinib and nilotinib. We also evaluated what proportion of patients become eligible to attempt to stop their TKI treatment. Methods: Chronic myeloid leukemia registry was analyzed to evaluate response rates in the first line and eligibility for a treatment cessation attempt in adults diagnosed between 2003 and 2019. The registry covered 60 patients. 46 eligible patients were included in the study. BCR-ABL1 levels of ≤ 0.1%, ≤0.01% and ≤0.0032% on the international scale were defined as the molecular response end-points major molecular response(MMR), MR4.0 and MR,4.5 respectively. In the case of a switch in TKI therapy, the clinical chart was reviewed for the reason why the treating physician had changed the therapy (‘treatment failure’ or ‘TKI intolerance’). For the determination of eligibility to stop TKI, the inclusion criteria for the EURO-SKI trial were applied. Results: Seventy-two percent of the patients were treated with imatinib, 28% with a second-generation tyrosine kinase inhibitor (nilotinib and dasatinib). 15% of patients had discontinued their first-line treatment, mainly due to intolerance (10%) or treatment failure (5%). At 24 months, deep molecular response (MR 4.0 and MR4.5) were achieved at 16.7% and 38.9% respectively for imatinib, and at 22.2% and 33.3% respectively for second generation (p=1). The 5-year cumulative incidence of eligibility for a tyrosine kinase cessation attempt, according to EURO-SKI criteria, was 37%. Conclusions: In the current study we report the experience in CML from two health care institutions in Beirut, Lebanon. Our findings showed no statistically significant difference in response between the first and second generations. The criteria for an attempt to stop tyrosine kinase inhibitor therapy are met by a third of the patients.
Integrative structural variant and breakpoint detection using optical genome mapping in a patient with a transformed diffuse large B-cell lymphoma from chronic lymphocytic leukemia.
Authors: Wang Jiachi , Pang Andy , Hong Karl , Lai Jill , Roychoudhury Dipa , Murata-Colllins Joyce L
Published: June 2021

e19511

Background: The finding of complex karyotypes has been a clinically significant finding in cancers of advanced stage or during cancer progression. Conventional cytogenetic and FISH analyses have been limited by the low-resolution of chromosomes and the number of FISH probes which can be implemented in one assay. Recent study revealed the potential of using optical genome mapping to decipher the architecture of cancer genome at nucleotide level. Methods: Karyotyping, FISH and optical genome mapping of bone marrow specimen. Results: We reported on a 63-year-old female with chronic lymphocytic leukemia for nine years and transformed to diffuse large B-cell lymphoma (DLBCL). The karyotype revealed a hypodiploid chromosomal complement: 42,X,-X,der(2)t(2;?;8)(p25;?;q11.2),t(2;9)(q3?5;p2?2),der(4)t(4;?;8)(p16;?;q11.2)t(4;15)(q35;q15),-8,-15,dic(17;21)(p11.2;p11.2),der(18)t(8;18)(q21.2;p11.32)[12]/46,XX[8]. FISH analysis showed loss of TP53, monosomy 8 with 3-5 copies of the Myc genes. Optical genome mapping analysis revealed 12 insertions, 29 deletions, 8 duplications, 6 intrachromosomal translocations and 12 interchromosomal translocations. Whole genome analysis identified multiple gains of 2p, 8p and 8q, losses of 9p, 15q and 17p. The breakpoints of two unbalanced translocation and one complex chromosomal rearrangement have been narrowed down to nucleotide resolution: ogm[GRCh37] t(2;9)(q34;p21.2) g.[chr2:211,281,003::chr9:26,532,620], ogm t(2;8)(p25.3;p23.3) g.[chr2:15,924::chr8:215,177] and ogm der(4)t(8q24.3→8q21.13→2p24.2→2q34→4p15.2→4q34.3→15q15.1) g.[chr8:80,461,191::chr2:18,079,530→chr2:211,274,379::chr4:26,381,729→chr4:180,989,408::chr15:42,404,514]. Conclusions: Integrative analysis using conventional cytogenetic and molecular cytogenomic methodologies unveil the complex architectural alterations of caner genome. The resolution achieved by optical genome mapping would potentially lead to discovery of carcinogenic mechanisms, new fusion genes, prognostic and therapeutic markers.
A retrospective study of efficacy and safety of mechlorethamine, vindesine, liposomal doxorubicin, and prednisone (MODP) in relapsed/refractory classical Hodgkin lymphoma.
Authors: Zhou Min-Hang , Wang Chunmeng , Liu Yang , Ku Wenjing , Yang Qingming , Han Weidong
Published: June 2021

e19516

Background: There are few optimized therapeutic options for relapsed and/or refractory classic Hodgkin’s lymphoma (r/rCHL), especially in patients who failed in treatments of autologous stem cell transplantation (ASCT), brentuximab vedotin or even immune checkpoint blockage. Therefore, we developed a chemotherapeutic scheme to evaluate the efficacy in r/rCHL patients with previous various lines of therapies. Methods: Between January, 2014 and December, 2019, a retrospective study was performed on r/rCHL patients from Chinese PLA general hospital who were treated with MOAP regimen consisting of mechlorethamine 6mg/m2, vindesine 4mg, liposomal doxorubicin 15mg/m2 on days 1 and 8, prednisone 1mg/kg per day on days 1 to 10 (MOAP) every 4 weeks. CT or PET/CT were done every two cycles to assess the response. Patients treated with MOAP regimen and complete clinical data were included. Patients with less than two cycles of MOAT or unavailable response assessment were excluded. The primary endpoint were complete remission (CR) and progression-free survival (PFS). Results: A total of 87 patients were included and five patients were excluded, so 82 patients were eligible in the study. The median previous lines and cycles of chemotherapy was 2 (range, 1-7), and 9 (range, 3-31), respectively. All the eligible patients received MOAP regimen for a median 4 cycles (range from 2 to 8), and overall response rate (ORR) was 87.8% including 40 patients in CR (48.8%) and 32 in PR (39.0%). In patients with ≥ 3 lines or ≥ 10 cycles of chemotherapy, up to 50.0% and 41.0% of patients achieved CR, respectively. In patients with previous ASCT, 31.6% of patients also achieved CR. Patients with previous checkpoint inhibitors had even higher CR than those without checkpoint inhibitors, though not significantly (51.6% vs. 47.1%, p = 0.689). Median PFS in patients with CR, PR and SD/PD were 43.8 months, 9.6 months and 6.1 months, respectively (p = 0.000).Patients with < 3 previous lines of chemotherapy had a favorable PFS than those with ≥ 3 previous lines (not reached vs. 14.4 months, (p = 0.032). No differences in PFS were observed in terms of previous cycles of chemotherapy, ASCT and checkpoint inhibitors. Grade ≥ 3 adverse events included 37 leukopenia (45.1%), 16 lung infection (19.5%), 11 anemia (13.4%), 4 thrombocytopenia (4.9%), 3 febrile neutropenia (3.7%) and 3 increased transaminase (3.7%). Conclusions: The MOAP combination regimen produced a favorable CR in r/rCHL failing or progressing on ASCT, checkpoint inhibitors, multiple cycles or lines of chemotherapies. It is an effective salvage regimen in heavily pretreated r/r CHL.
Resource use and costs in patients with relapsed/refractory diffuse large C-cell lymphoma who initiated a third-line therapy in the post CAR-T era: A longitudinal outlook.
Authors: Chen Lei , Xie Jipan , Wu Aozhou , Liao Laura , Du Ella X. , Noman Ahmed , Nastoupil Loretta J.
Published: June 2021

e19560

Background: The study described longitudinal costs and healthcare resource utilization (HRU) associated with third-line (3L) treatments in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) post chimeric antigen receptor T-cell (CAR-T) approval. Methods: Adult patients newly diagnosed with DLBCL (ICD-10: C83.3) from 10/01/2015 to 03/31/2020 and receiving 3L after CAR-T approval (10/18/2017) were identified from IQVIA PharMetrics Plus. Monthly HRU and total costs were evaluated during month 1, months 2-6, and months 7-12 following 3L initiation for three treatment groups: CAR-T, stem cell transplantation (SCT), and non-cell therapy including chemoimmunotherapy and the targeted therapies that are recommended by the NCCN guidelines (including brentuximab vedotin, ibrutinib, venetoclax, lenalidomide, polatuzumab, obinutuzumab, nivolumab and pembrolizumab). Results: The study identified 145 R/R DLBCL patients initiating 3L with a mean age of 56.7 years and 66.2% male; 135 patients with ≥1 month of follow-up (median 6.7 months) were included: 24 CAR-T, 15 SCT, 96 non-cell therapy. At each time period, CAR-T had the highest median monthly costs, followed by SCT; both had higher median costs than non-cell therapy. The median monthly costs for CAR-T and SCT were $205,034 and $160,423 in month 1, and reduced to $14,333 and $11,840 in months 2-6, then increased to $27,090 and $17,695 in months 7-12, respectively. The monthly median cost for non-cell therapy was $36,015, $11,878, and $4,806 in month 1, months 2-6 and 7-12, respectively. Inpatient (IP) visits and IP days were higher in month 1 than later months for CAR-T and SCT. In addition, outpatient (OP) and emergency room (ER) visits were more frequent for CAR-T than SCT except for ER visits in month 1 (Table). Conclusions: In R/R DLBCL patients receiving 3L, CAR-T had the highest median monthly costs during month 1, months 2-6 and 7-12. In addition, CAR-T has more frequent OP and ER visits compared with SCT in general.[Table: see text] The maximum observed follow-up time for SCT was 8 months. Other visits were mainly home care visits.
Limited stage mantle cell lymphoma: Results of overall survival based on treatment modality using SEER database.
Authors: Jayarangaiah Apoorva , Wang Shuai , Elrafei Tarek N. , Steinberg Lewis , Kumar Abhishek
Published: June 2021

e19566

Background: Limited stage mantle cell lymphoma (MCL) (stage I-II) is rare and occurs in 5-15% of patients. The ideal treatment approach among radiation (RT), chemotherapy (CT), chemoradiotherapy (CRT) or close monitoring (NT) has not been defined. Methods: A retrospective analysis of SEER database (1975 to 2018) was conducted for patients with stage I-II MCL to compare overall survival (OS) among the various treatment modalities in patients >18 years. We excluded patients lacking information on demographic characteristics and survival. Patients were analyzed in 4 groups; RT only, CT only, CRT and no treatment groups. ANOVA test and Chi-square test were used to evaluate parametric and non-parametric variables between groups, respectively. Cancer specific survival (CSS) and OS were assessed by Kaplan-Meier. SPSS 26.0 was used for data analysis. Results: There were in total 2266 patients with limited stage MCL. Median age was 71 years (61-78.25) and predominantly male (65.7%). Stage I MCL was noted in 55.6% and stage II in 44.4% of the patients. The number of patients in each group; RT only, CT only, CRT and NT along with the OS are presented in Table. CSS among these four groups showed no statistically significant differences (p <0.26). OS showed that CT only group has worse survival compared to RT only and CRT groups (p <0.001). CRT has no significant difference in survival compared to RT only (p<0.001). NT was associated with poorest survival rates (p<0.001). Conclusions: In limited stage MCL, RT only and CRT resulted in superior OS compared to CT only. Results suggest a role for incorporation of RT in treatment regimens. One limitation of the study is that the SEER database lacks the ability to distinguish between no receipt of therapy versus lack of availability of data.[Table: see text]
A systematic review of post-transplant lymphoproliferative disorder after renal transplantation.
Authors: Zamani Zarlakhta , Haider Mobeen Zaka , Taqi Muhammad , Mirza Hasan Mehmood , Kumar Deepak , Shahid Hafsa , Kiran Fnu , Khalid Yousra , Mughal Mohsin Sheraz , Akbar Usman Ali , Faisal Muhammad Salman , Mushtaq Muhammad Umair , Anwer Faiz
Published: June 2021

e19577

Background: Post Transplant Lymphoproliferative Disorder (PTLD) is a rare but severe complication following renal transplant. This study aims to explore the treatment modalities, histological types, and risk factors related to PTLD. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase & clinicaltrials.gov. A total of 1741 articles were screened and 16 studies were included. Results: We reviewed 275915 adult patients who underwent renal transplantation out of which 2484 (0.9%) patients developed PTLD. Data for gender shows that 61.1% were males and 38.9% females. 576/2484 (23%) cases were EBV positive post-transplant. Seven studies showed the median duration from transplant to the development of PTLD was 80 months (5m-22yrs). Monomorphic PTLD was reported in 585 cases as the most common histological type. 5 studies suggested mortality due to PTLD was 41.38%. OS at 5 and 10 years was 55% and 41% respectively. Conclusions: Our study shows that PTLD is a rare complication after renal transplant which was more common in males. EBV did not show association with PTLD. Monomorphic is the most common histological type of PTLD after renal transplant. Our results show that it is associated with significantly high mortality. [Table: see text]
Daratumumab, pomalidomide, and dexamethasone in relapsed refractory multiple myeloma (RRMM): A comparison with contemporary clinical trials.
Authors: Paul Barry , Robinson Myra M. , Robinson Jordan , Ndiaye Ami , Bhutani Manisha , Voorhees Peter Michael , Symanowski James Thomas , Friend Reed N. , Pineda-Roman Mauricio , Usmani Saad Zafar , Atrash Shebli
Published: June 2021

e20011

Background: Multiple Myeloma (MM) is an incurable malignancy of terminally differentiated plasma cells. The combination of pomalidomide/dexamethasone with either daratumumab or isatuximab is FDA approved for relapsed refractory multiple myeloma (RRMM) based on randomized phase III trial data. Herein, we compare our center’s experience with published data to help identify the most appropriate patient population for this regimen outside of the context of clinical trials. Methods: We interrogated our internal plasma cell disorder database to identify all patients with RRMM at our institution who were treated with the combination of daratumumab, pomalidomide, and dexamethasone (Dara-Pd). We evaluated the best response achieved, overall response rate (ORR), progression free survival (PFS), and overall survival (OS) measured from initiation on Dara-Pd. Kaplan Meier methods were used to estimate PFS and OS curves. Fisher’s exact tests and log rank tests were used to determine the association between outcomes and variables of interest. Results: Between Dec 2015 and Dec 2020, 98 patients were identified, of which 97 were evaluable for response. Median number of prior lines of therapy was 2 (range 1-12), with 23 patients (23%) previously treated with 3 prior lines and 24 patients (25%) previously treated with ≥4 lines of therapy. Most patients were refractory to an IMiD (79.6%), a PI (65.3%), or both (56.1%). The ORR was 69.1%, > VGPR rate was 33%. ORR was significantly improved for patients who received Dara-Pd after 1 line (p = 0.03), but depth of response (≥VGPR), was similar (p = 0.62). At a median follow up of 10.8 months, 1-year PFS was 76.6% in patients after 1 line, 38.8% in patients after 2-3 lines, and 35% in patients after > 4 lines. Overall response rates appear comparable to published phase III trials comparing the combination of Pd with or without an anti-CD38 monoclonal antibody (Table 1). While PFS was somewhat lower in our population, subset analysis showed that PFS was significantly lower in patients who were PI refractory (10.8 months vs 6 months; p = 0.014), and in patients who were both IMiD and PI refractory (20.4 months vs 6 months p = 0.01), but OS was similar in these populations. Conclusions: Our data suggests that the combination of Dara-Pd has activity in heavily pretreated patients, including patients who are both IMiD and PI refractory and remains a viable option for these patients outside the context of a clinical trial.[Table: see text]
Acute and chronic cancer-related distress among multiple myeloma patients during the COVID-19 pandemic.
Authors: Ahlstrom Jenny , Molina Thomas H. , Sweeney Nathan W.
Published: June 2021

e20025

Background: Patients with multiple myeloma (MM) are uniquely susceptible to viral and bacterial illnesses. In addition, MM and its treatments lead to immune deficiency, putting patients at a high risk for infection, including the novel coronavirus (COVID-19). The emotional impact of COVID-19 on high-risk groups, such as MM patients, remains unclear. The purpose of this project was to understand psychosocial distress and unmet needs among patients with active MM during the acute and chronic phase of COVID-19 and its impact in the United States. Methods: We utilized the HealthTree Cure Hub (healthtree.org) and invited patients with active MM cancer or precursor conditions to participate in an online CancerSupportSource distress screening questionnaire by the Cancer Support Community. Participants were asked to rate their level of concern (Not at All to Very Seriously) on 12 items assessing physical, psychosocial, and practical needs during the acute and chronic phase of the COVID-19 pandemic. De-identified responses were aggregated and reviewed. Results: 1,079 MM patients analyzed during the acute phase of the pandemic (April 15, 2020, to June 8, 2020) and 246 were analyzed during the chronic phase (January 8, 2021, to February 12, 2021). The percent of patients responding moderately to very seriously concerned are reported here. While eating and nutrition increased 3% from acute (71%) to chronic (74%) phases, physical needs overall decreased 2%. Psychosocial needs (worrying about the future, family concerns, feeling irritable, sad, nervous, or lonely, and relationship concerns) decreased 4% between the two phases, despite the 2% increase in problems with your spouse/partner. Additionally, practical needs (health insurance or money worries) decreased 4% between the acute and chronic phases of the pandemic. Conclusions: Respondents to our survey maintain a concern for eating and nutrition during the acute and chronic phases of the pandemic. Between the three types of needs examined in this survey, physical needs had the smallest change over time. This information can inform patients and medical professionals of the type of distress experienced by patients and help investigators assess the needs of the patient community to enhance patient outcomes.[Table: see text]
A pilot study of physical activity in newly diagnosed elderly patients with multiple myeloma.
Authors: Binder Adam F , Spinelli Bryan , Melillo Rebecca , Crane Nicole , D'Adamo Laura , Martinelli Mary K , Martinez-Outschoorn Ubaldo , Butryn Meghan
Published: June 2021

e20027

Background: Compared to a baseline normative population, patients with multiple myeloma (MM) have decreased physical function[1]. Studies have revealed that sarcopenia[2, 3], decreased performance status[4], and poor performance on biometric testing[3, 5] predicts worse survival in patients with advanced, incurable malignancies. Physical activity (PA) has been shown to mitigate these effects and in some cases improve cancer specific survival [6-9]. However, there is a need for further research in this area for patients with hematologic malignancies. Here in we describe the results of a pilot study to assess a physical activity intervention in elderly patients with newly diagnosed multiple myeloma. Methods: We designed a single arm, feasibility study utilizing physical and behavioral therapy interventions to help participants adhere to a prescribed exercise program. Eligible patients (age ≥65 years old) were recruited from the multiple myeloma treatment clinic. Baseline, 3-month and 6-month assessments occurred. The intervention included both text messaging and video visits with behavioral coaches and physical therapists to monitor activity levels, review and modify exercise plans, , and enhance motivation and self-efficacy. Our primary aim was to establish the feasibility of recruitment, enrollment, and adherence of the exercise intervention. Our secondary objective was to evaluate changes in fitness (6 minute walk test, grip strength, and the Short Physical Performance Battery). Results: Between 11/18/2019-03/04/2020, 9 participants enrolled on the study (goal of 20). New enrollment was halted due to the COVID-19 pandemic. Median age of the participants was 70 (range 65-86). Six (67%) were female. Eight participants (89%) completed the 6-month intervention. Participants completed 97.8% of the scheduled visits. At 3 and 6 months there was a mean change of moderate/vigorous activity of 26.0% (SD 89.6%) and -0.5% (SD 56.4%) respectively. At 3 and 6 months there was a mean change in step count per day of -5.1% (SD 25.3%) and -1.3% (SD 32.2%) respectively. Overall fitness was preserved over the 6-month period. Conclusions: Prior to COVID-19 pandemic, the study was on track to meet feasibility endpoints of recruitment, enrollment, and retention. The primary endpoint of increasing physical activity was not met. However, adults in our region experienced a 20-30% reduction in physical activity during the pandemic [10]. In the target population, reductions in the absence of intervention may have been even greater, given their pronounced vulnerability to COVID-19 complications. Thus, the true benefits of the intervention may have been difficult to detect during this period. Lack of a control arm is a limiting factor in making further conclusions about the potential benefits of our intervention.
Bispecific CART cells in the treatment of relapsed and refractory multiple myeloma: A review of literature.
Authors: Christy Joshua , Rafae Abdul , Hanif Nazma , Pachika Pranali Santhoshini , Kandah Emad , Ehsan Hamid , Wahab Ahsan , Saleem Tabinda , Ali Rabia , Malik Mustafa Nadeem , Anwer Faiz
Published: June 2021

e20038

Background: Chimeric antigen receptor T cells (CART) have shown promising results in the treatment of relapsed and refractory multiple myeloma (RRMM). Recently, bispecific-CART cells targeting 2 antigens are being evaluated in various clinical trials. Methods: A comprehensive literature search was done of Pubmed, Embase, and Cochrane. Data presented at annual hematology and oncology conferences were also included. Results: We included 4 phase I clinical trials with a total of 77 RRMM patients between the ages of 18 to 71 years. The median follow-up duration ranged from 1 month to 27.5 months. All were lymphodepleted with Cyclophosphamide and Fludarabine before receiving CAR-T cell therapy. The CAR-T cell targets include BCMA and CD38 (dose range 0.5 x 10^6 - 4 x 10^6 cells/kg), BCMA and TACI (dose range 15 - 900 x 10e6 CAR-T cells), BCMA and CD19 (1 x 10e5/kg - 3 x 10e5 CAR-T cells/kg), and BCMA and CD19 (dose 1 x 10e6 cells/kg). Overall response rate (ORR) was reported by 4 trials (87.5%, 43%, 93.8%, 95%). Complete response (CR) was also reported in 4 trials as 50%, 64%, 56.3% and 14% and partial response (PR) reported as 25%, 28%, 16.6%, 14%, 18% in 5 trials (table). The most common grade 3-4 adverse effects that were reported include cytokine release syndrome, neurotoxicity, neutropenia, lymphopenia, anemia, thrombocytopenia, diarrhea, increased LDH, lower respiratory tract infections (LRTI), dehydration, renal failure (table). Yan et al. reported one death due to cerebral hemorrhage which was considered unrelated to treatment. Jiang et al. reported one death from unknown cause of a patient who presented with fever during the COVID- 19 pandemic. Conclusions: Bispecific CART cells have shown promising results in the treatment of RRMM. However, the clinical trials are ongoing, and a longer follow-up is needed.[Table: see text]
Integrative medicine and plasma cell disorders.
Authors: Okolo Onyemaechi , Wertheim Betsy C. , Larsen Ashley , Sweeney Nathan W. , Gowin Krisstina L.
Published: June 2021

e20044

Background: Recent advancements in the treatment of plasma cell disorders (PCD) have led to a revolution in treatment options. Despite improved outcomes, patients have unmet symptom management needs. Integrative medicine (IM) is a method for addressing symptoms in cancer, but its use and efficacy is poorly defined in PCD patients. This analysis describes the utilization of IM among myeloma patients and explores associations with symptom burden. Methods: For 3 months, a 70-question online survey was hosted on HealthTree.org, an online resource for myeloma patients and researchers created by the HealthTree Foundation. The survey included questions about demographics, PCD type, disease stage, complementary practice use, PHQ-2 score (depression screen), and quality of life (sum of 6 interference items; possible score range 0-6). Mean outcome values were compared between IM users and non-users using two-sample t-tests. Proportions of supplement users and IM users were compared between patients currently on myeloma-specific treatment and patients not currently on treatment using chi-square tests. Results: Of 195 total respondents, 17 were excluded for not completing the survey section on IM practices. Median age range was 60-69 years old, 61% were female, 91% were non-Hispanic white, and 57% were overweight or obese. Plasma cell subtypes were active myeloma (81%), smoldering myeloma (12%), MGUS (3%), amyloidosis (2%), and plasmacytoma (1%), and 72% of patients were currently on cancer-specific treatment. On a scale of 1-10 (1=very uncomfortable; 10=very comfortable), patients reported a mean score of 3.7 when discussing IM therapies with their oncologist. The top 10 IM modalities reported were aerobic exercise (83%), nutrition (67%), natural products (60%), strength exercise (52%), support groups (48%), breathing exercises (44%), meditation (42%), yoga (40%), mindfulness-based stress reduction (38%), and massage (38%). Those who participated in meditation had significantly higher PHQ-2 scores (worse depression) than non-participants (1.1 vs. 0.8; p=0.05). Users of support groups (3.4 vs. 2.7; p=0.04), medicinal marijuana (4.0 vs. 2.9; p=0.03), or vitamin C (3.6 vs. 2.7; p=0.01) reported higher mean interference (worse quality of life) than non-users. Compared to patients currently on cancer treatment for PCD, untreated patients were significantly more likely to use curcumin (58% vs. 41%; p=0.04) or green tea (44% vs. 17%; p<0.001), were less likely to use medicinal marijuana (6% vs. 18%; p=0.05), and reported significantly lower fatigue (p=0.02). Conclusions: This international survey-based analysis reveals that most patients participated in IM modalities, though felt uncomfortable discussing them with their oncologist. It is unclear if the use of some IM modalities were due to symptom burden or lead to higher symptom burden. This study provides a foundation in the understanding of IM use in PCD, but more research is needed to evaluate its efficacy.
Germline mutations among patients with non-small cell lung cancer.
Authors: Yang Tongtong , Liu Huanhuan , Li Mingwei , Zhang Yanrui , Zhang Yun , Liang Xiayuan , Lou Feng , Cao Shanbo , Wang Huina
Published: June 2021

e20527

Background: Lung cancer is currently a leading cause of cancer-associated mortality worldwide. Germline mutations potentially predisposing patients to lung cancer have not been systematically defined. In this study, we sought to determine the prevalence of pathogenic/likely pathogenic (P/LP) germline mutations in patients with NSCLC. Methods: A total 1562 patients with NSCLC were included in this study. Leukocyte DNA was extracted and detected were using next generation sequencing technology. Allele frequencies were compared with publicly available database. Interpretation of sequence variations was classified according to the American College of Medical Genetics and Genomics guidelines. Results: Overall, median age at testing of individuals was 63 years (range 12 to 91). The majority of individuals tested were male (56.15%, 877/1562). of 1562 NSCLC, P/LP mutations were identified in 94 (6.02%) in 42 Cancer Susceptibility genes. No individuals carried more than 1 germline variant. The most common P/LP mutations in genes were MUTYH (n = 11, 0.70%), TP53 (n = 10, 0.64%), BRCA2 (n = 8, 0.51%), PALB2(n = 5, 0.32%), PTEN(n = 4, 0.26%), BLM(n = 3, 0.19%), WRN(n = 3, 0.19%), and ATR, BRCA1 and BRIP1 (n = 2, 0.13% each). Twenty eight patients were carried germline mutations in homologous recombination repair(HRR), including BRCA2 (8), PALB2 (5), PTEN (4), BRCA1 (2), BRIP1 (2), CHEK2 (2), FANCA (2), ATM (1), RAD51B (1), RAD54L(1). Of note, the clinical features of patients with HRR mutations were not young adult (median age [range], 57 [41-80] years). Conclusions: Of 1562 patients with NSCLC, 94 (6.02%) had germline mutations and 27 (1.73%) had mutations in HRR genes. The presence of HRR germline mutations could guide cancer screening for patients and their families and serve as predictive biomarkers of response to targeted or immunotherapies. More extensive germline testing in NSCLC should be considered.
Chemoradiation-induced pneumonitis in patients with unresectable stage III non-small cell lung cancer: A meta-analysis.
Authors: Pierce Christine , Kuang Yuting , Chang Hsiu-Ching , Nevo Arianna , Deitz Anne , Keller Steven M. , Piperdi Bilal , Uyei Jennifer
Published: June 2021

e20532

Background: Recent clinical trials have shown positive results for therapies combining concurrent chemoradiation therapy (cCRT) and checkpoint immunotherapy in unresectable non-small cell lung cancer (NSCLC). cCRT is associated with an increased risk of pneumonitis, a severe and life-threatening inflammation of the lungs. To further inform clinical decision-making and support the evaluation of new therapies combining immunotherapies with cCRT, it is important to understand the baseline risk of pneumonitis associated with cCRT alone. The objective of this study was to quantify the incidence of cCRT-induced grade 3−5 pneumonitis (immune-mediated and radiation pneumonitis) in unresectable stage III NSCLC patients. Methods: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to April 24, 2020. Chemotherapies of interest were cisplatin, pemetrexed, etoposide, carboplatin, and paclitaxel. Randomized controlled trials (RCTs), observational studies, and non-randomized trials were included. Bayesian meta-analysis using a binomial model random effects model was conducted with SAS 9.4. Results: Among 1,889 records identified from the search, 17 studies (6 RCTs, 8 observational studies, 3 single-arm trials) met inclusion criteria. Eleven studies were included in the meta-analysis (5 RCTs, 6 observational studies; 1,788 patients). All studies specified radiation-related pneumonitis (RP), although this is clinically indistinguishable from immune-mediated pneumonitis. Patient populations were comparable across studies; the most common chemotherapies were paclitaxel + carboplatin (n = 6) and pemetrexed + cisplatin (n = 5), and radiation doses ranged from 60–74 Gy. There was variation across studies in intervention, outcome reporting, and follow-up (median range: 12–73 months), but this variation was considered acceptable based on sensitivity analyses. The estimated pooled incidence of grade 3−5 RP in cCRT-treated unresectable stage III NSCLC patients was 3.62% [95% confidence interval (CI): 1.65−6.21] in RCTs and 5.98% [95% CI: 2.26−12.91] in observational studies. The pooled incidence of fatal (grade 5) RP was 0.37% [95% CI: 0−2.78] in RCTs and 1.73% [95% CI: 0.53−4.33] in observational studies. Conclusions: This study estimates that 3.62–5.98% of patients with unresectable stage III NSCLC develop grade 3−5 RP when treated with cCRT, with incidence varying by study design. Estimates of RP incidence were higher in the real-world setting compared to RCTs. These results can be used to contextualize the baseline risk of cCRT-induced pneumonitis in unresectable stage III NSCLC to better understand the adverse event of pneumonitis associated with novel immunotherapy treatments indicated for concomitant use with this modality.
Observed survival benefit with limited exposure of durvalumab in unresectable stage III non-small cell lung cancer at a large community-based institution.
Authors: Vadehra Deepak , Pallas Christopher R , Moore Donald , Villadolid Jeryl Jean , Robinson Myra M. , Mileham Kathryn Finch , Carrizosa Daniel R.
Published: June 2021

e20539

Background: The PACIFIC trial ushered in a paradigm shift in the management of unresectable, non-metastatic non-small cell lung cancer (NSCLC), demonstrating improvement in 12,24,36-month overall survival (OS) and leading to the 2018 FDA approval for durvalumab in unresectable or locally advanced stage III NSCLC. With almost 3 years of FDA approval, we performed a retrospective analysis of patient experiences and outcomes at Levine Cancer Institute analyzing patient data to assess survival and potential points of clinical significance. Methods: Patients over the age of 18, who met criteria similar to the PACIFIC trial (i.e. unresectable or locally advanced stage III NSCLC) from February 2018 through September 2020 were analyzed. Those who were receiving active treatment at the data cutoff were excluded. Patient characteristics, prior treatment, durvalumab administration, immune-related adverse events (irAEs), and efficacy data were summarized and evaluated. OS and progression free survival (PFS) were evaluated with Kaplan Meier methods. Results: A total of 159 patients were evaluated. 40.9% were female and 59.1% were male. The median age was 67 (range 38-83 years). Of note, 86.8% of patients were white, whereas 13.2% were nonwhite. 50.3% patients experienced an irAE. The most common reasons for discontinuation of durvalumab were completion (at least 24 doses), progressive disease, or toxicity (33.3%, 30.8%, 26.4%, respectively). The median number of doses of durvalumab received was 14 (range 1-26 doses). The median PFS was 15.3 months with 12-and 24-month PFS being 54% and 41.1 %, respectively. Median OS was 42 months with 12-and 24-month OS being 78.1% and 67.8%, respectively. Our analysis compared outcomes in those who completed adjuvant durvalumab versus those who did not complete adjuvant therapy (Table). Conclusions: Data shows the best survival in those who completed durvalumab (comparable to historic values) and novel data shows a perceived survival benefit in those completing 12 doses compared to those who did not. Thus, partial treatment may provide a survival advantage. Further multivariate analysis will look for possible correlations to increased immune events and inability to complete therapy. Further investigation will delve into this cohort’s small proportion of non-white patients, evaluating for possible barriers to care that may lead to more patients being diagnosed with stage IV NSCLC.[Table: see text]
Molecular and clinical characteristics of primary pulmonary lymphoepithelioma-like carcinoma.
Authors: Fan Ying , Shan Qian Yun , Gong Jia Li , Qin Jing , Lu Hongyang
Published: June 2021

e20541

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an extremely rare subtype of non-small cell lung cancer (NSCLC) and there are no established treatment protocols due to its rarity. At present there are only limited studies about the molecular and clinical characteristics of PPLELC and the results are often inconsistent. Methods: The study collected patients with PPLELC who were admitted to Zhejiang Cancer Hospital from 2009 to 2020 retrospectively. Next-generation sequencing (NGS) was performed to obtain a more comprehensive mutation profile of PPLELE, tumor mutation burden (TMB) level and the expression of programmed cell death 1 ligand 1(PD-L1) was detected for 7 patients. In addition, we review the studies concerning the immunotherapy of advanced PPLELC. Results: 18 patients diagnosed as PPLELC pathologically were collected. 71.4% (5/7) patients expressed PD-L1 (≥ 1%) and the median TMB was 2.5 mutations/Mb. TP53 (43%) and CYLD (43%) were the two most common mutations and other variants included LRIG1 (14%), PTPRT (14%), PPP2R2A (14%). 15 patients survived, 3 patients died and 1 patient was lost after a followed up time for 8.8 to 138 months. A total of 11 cases of advanced PPLELC patients who received immunotherapy were analyzed retrospectively and the disease control rate (DCR) was 90.9%. Conclusions: The prognosis of PPLELC is better than that of other NSCLC and immunotherapy may be a promising treatment to prolong the survival time of advanced PPLELC.Whether the immunotherapy efficacy of PPLELC can be predict by PD-L1 and TMB is worthy of further clinical research. CYLD genetic alterations may participate in Epstein-Barr virus (EBV) -mediated tumorigenesis in PPLELC and expected to provide a new therapeutic target.
Treatment patterns and characteristics in the second and third-line therapy setting for real-world small cell lung cancer patients.
Authors: Prince Patricia , Estrin Adina , Supina Dylan , Ben-Joseph Rami , Boccuti Anne , Asubonteng Kobby , Rengarajan Badri , Fridman Moshe , Hanvesakul Raj , Taylor Benjamin
Published: June 2021

e20576

Background: With emerging treatment options for small-cell lung cancer (SCLC) patients after initial treatment failure, the real-world management of this disease should be assessed. This study aims to describe treatment patterns of real-world SCLC patients in the second-line therapy (2L) and third-line therapy (3L) setting. Methods: This was a descriptive study of real-world data sourced from ConcertAI electronic medical records, including data from CancerLinQ, an initiative of the American Society of Clinical Oncology of adults (age ≥ 18 years) with confirmed SCLC between January 1, 2016 and December 31, 2018. Patients were excluded based on evidence of other primary cancer at baseline, missing stage, death prior to diagnosis, or clinical trial participation. Patients entered the cohort on their SCLC diagnosis date and were followed through three tumor progressions to assess treatment patterns. Treatment patterns were assessed in 2L and 3L. Baseline characteristics were assessed in the 6 months prior to each line. Patients were classified as having unknown treatment if they had a gap in medical records > 90 days or no recorded tumor response or death within 180 days. Results: Overall, 538 patients were identified; 131 with unknown treatment, 108 with no treatment, 299 with 1st line therapy (1L), 124 with 2L, and 44 3L. The majority (76%) of patients were diagnosed in a community hospital setting. The most common comorbidities were chronic obstructive pulmonary disease (2L 25%, 3L 16%), diabetes (2L 15%, 3L 14%), congestive heart failure (2L 7%, 3L 9%), and myocardial infarction (2L 3%, 3L 2%). Radiation therapy was commonly used in 2L and 3L (2L 48%, 3L 43%) as were immunotherapies (2L 23%, 3L 23%). The most common systemic therapy in 2L and 3L was nivolumab (19% and 16%). Topotecan accounted for 11% of patients treated in 2L and 7% of those in 3L. Conclusions: During this treatment era (pre-immunotherapy 1L approval) there were limited treatment options available for SCLC patients. Radiation therapy and immunotherapies were frequently used as 2L and 3L therapy.[Table: see text]