bluuebunny/crossref_metadata_2025 huggingface dataset:
A community oncology practice financial experience in oncology care model pilot (OCM).
Authors: Akhtar Adil Jamal , Margolis Jeffrey H. , Sheth Karna , Maxwell Karma , Muskovitz Andrew A. , Zekman Richard Philip , Howard George , Ballouz Samer , Qamruzzaman Yusuf , Balaraman Savitha , Ibrahim Mohammed , Fabbiano Maria , Folbe Mitchell , Ogaily Mohammed S. , Stortz Lexi , Pancholi Shehnaz , Tauquir Anoosha Maria
Published: May 2020

e19379

Background: Oncology Division of Michigan Health Professionals (MHP) participates in OCM, which requires effort from all MHP OCM providers to coordinate care at same or lower cost to Medicare. Palliative Care, Care Management, and End of Life Care programs established by MHP, in collaboration with Premiere Hospice and Integra Connect, have shown cost and quality benefits in the OCM patients. Quality improvement initiatives included monthly OCM provider meetings to review OCM results, identify cost & quality opportunities, and to design training and education sessions. In order to assess the impact of such a concerted initiative, this study aims to evaluate MHP OCM provider impact in OCM total cost of care relative to historical period. Methods: Retrospective review of reconciliation results provided by Centers for Medicare and Medicaid Innovation (CMMI) for OCM performance periods 1-4 (pp1-4). Total cost of care (ACTUAL) and cost categories were the summarized and adjusted expenditures during 6-month OCM period as reported by CMMI. ACTUAL and cost category experience was compared by OCM performance period to the trended-mean of matched historical OCM-eligible patients (Baseline Episodes from CMMI). Patients were matched by cancer type, comorbidity count, age group, radiation, surgery, and low-intensity/-risk cancer sub-type for prostate, bladder and breast cancers. Results: The largest pp1-4 cost category reductions were acute inpatient ($2.2M), physician services excluding drug-cost, imaging and labs ($1.2M), skilled nursing facility ($0.5M), ancillary which consists of imaging and lab ($0.5M), inpatient rehab ($0.3M), home health agency ($0.3M), radiation oncology ($0.1M). The largest pp1-4 increase in OCM expense relative to historical was Part D Drugs ($1.7M). Conclusions: MHP decreased non-drug costs by $5.1M compared to historical cost for matched patients. OCM costs were lower in facility (hospital and SNF) and physician sites of care. Drug costs increased by $1.7M. Study was limited by OCM claims available as of December 2019. Results may be refreshed as more data becomes available. [Table: see text]
Cost-effectiveness of combined atezolizumab/nab-paclitaxel for advanced triple-negative breast cancer.
Authors: Salans Mia A , Cherry Daniel R , Yip Anthony T , Courtney Patrick T , Kumar Abhishek , Murphy James Don
Published: May 2020

e19388

Background: The IMpassion 130 trial found prolonged progression-free and overall survival among PD-L1-positive, advanced triple-negative breast cancer (TNBC) patients receiving atezolizumab and nab-paclitaxel versus nab-paclitaxel alone. These results were the basis of the first FDA approval of a breast cancer immunotherapeutic agent. With the high cost of combined therapy we present a cost-effectiveness analysis of the addition of atezolizumab to nab-paclitaxel for the treatment of advanced TNBC in PD-L1-positive patients. Methods: We constructed a Markov model to simulate cancer progression, survival, and toxicity in advanced TNBC patients receiving atezolizumab and nab-paclitaxel compared to nab-paclitaxel alone. Transition probabilities were derived from the IMpassion 130 trial, while costs (in 2019 US dollars) and health utilities were estimated from the literature. Cost effectiveness was assessed with incremental cost-effectiveness ratios (ICERs), expressed as dollar per quality-adjusted life-year (QALY), with values of less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results: Our base-case model found that treatment with atezolizumab and nab-paclitaxel increased overall cost by $120,800 and improved effectiveness by 0.11 QALYs compared with nab-paclitaxel alone, leading to an ICER of $1,101,000/QALY. The base-case model was not sensitive to any single variable. Women in the combined atezolizumab and nab-paclitaxel arm spent more time with stable disease before progression and with progressive disease before death compared to those treated with nab-paclitaxel alone. In our base-case analysis the addition of atezolizumab was not cost effective at any price of atezolizumab secondary to the high costs of stable and progressive disease. If we assumed lower costs of stable disease and progression, our model became sensitive to the cost of atezolizumab. A probabilistic sensitivity analysis found that adding atezolizumab would be cost ineffective 99.9% of the time at a willingness-to-pay of $100,000/QALY. Conclusions: Despite improved clinical outcomes, the addition of atezolizumab would not be considered cost effective in part due to the high costs of stable disease and disease progression among women with advanced TNBC. Novel therapeutics in this costly patient cohort will need to bend the cost curve of stable and progressive disease before becoming cost effective at thresholds acceptable by today’s standards.
Comparing total cost of care for Medicare FFS patients with pancreatic cancer by chemotherapy regimen.
Authors: Hirsch Jared , Dieguez Gabriela , Cockrum Paul
Published: May 2020

e19394

Background: To analyze total cost of care for patients with pancreatic cancer by common therapeutic regimens. Methods: Cancer episodes were identified using a methodology similar to the Medicare Oncology Care Model (OCM) in the 2014-2016 100% Medicare Limited Data Set (LDS) claims files. Index dates for chemotherapy claims could not occur within 6 months of another chemotherapy claim for all Medicare FFS beneficiaries. Cancer episodes were defined as the 6-month period following an index date. Each episode was assigned a cancer type based on the plurality of cancer ICD 9/10 diagnosis codes that occurred on chemotherapy claims in the episode. Episode costs were calculated from claims paid amounts. DME and other Part B spending was estimated using episodes from the 5% Medicare LDS files using the same methodology. We analyzed total episode costs for five pancreatic cancer treatment regimens: gemcitabine plus nab-paclitaxel (gem-nab), FOLFIRINOX, liposomal irinotecan, FOLFOX, and FOLFIRI. Results: We identified 110,618 cancer episodes in 2016, of which 4,018 were pancreatic cancer. Pancreatic cancer patients in these episodes were treated with gem-nab (45% of episodes), FOLFIRINOX (14%), FOLFOX (8%), FOLFIRI (6%), and liposomal irinotecan (4%). The main drivers of episode costs among regimens were Part B chemotherapy, other Part B drugs, and inpatient services. Episode costs were $41,749, $42,086, $35,601, $36,169, and $45,851 for patients receiving gem-nab, FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan, respectively. Part B chemotherapy costs were $13,065 (gem-nab), $3,095 (FOLFIRINOX), $4,853 (FOLFOX), $3,204 (FOLFIRI), and $18,474 (liposomal irinotecan); other Part B drug costs were $7,343 (gem-nab), $17,013 (FOLFIRINOX), $11,131 (FOLFOX), $15,377 (FOLFIRI), and $10,479 (liposomal irinotecan); and inpatient service costs were $9,044 (gem-nab), $9,069 (FOLFIRINOX), $7,701 (FOLFOX), $5,838 (FOLFIRI), and $5,108 (liposomal irinotecan). Conclusions: Total episode costs for pancreatic cancer care ranged from $35,601 (FOLFOX) to $45,851 (liposomal irinotecan), but the cost components varied by regimen. Episodes with liposomal irinotecan had the largest Part B chemotherapy costs but the lowest inpatient service costs. Episodes with FOLFIRINOX and gem-nab had similar inpatient service costs, which were higher than episodes with liposomal irinotecan, FOLFOX, or FOLFIRI. Episodes with FOLFIRINOX and FOLFIRI had higher other Part B drug costs than episodes with FOLFOX, liposomal irinotecan, or gem-nab.
Experience of financial burden and distress among people with ovarian cancer.
Authors: DeRosa Branlyn W. , Zaleta Alexandra Katherine , Johnson Angela J. , Clark Kelly A. , Ackourey Jemeille , DeFeo Sarah , Donziger Marcia , Friedman Sue J. , La Cava Shannon , Lee Nita Karnik , Salani Ritu , Wright Alexi A.
Published: May 2020

e19400

Background: The impact of ovarian cancer (OC) is wide-reaching; this study explored cancer-related financial burden related to cost of care in people ever diagnosed with OC. Methods: 64 OC patients enrolled in Cancer Support Community’s Cancer Experience Registry. Participants provided demographic and clinical history, and completed 1) CancerSupportSource, a validated 25-item tool with anxiety and depression risk subscales, and 2) the 11-item COmprehensive Score for financial Toxicity (COST). Descriptive statistics were calculated for responses; Pearson/Spearman correlations and one-way ANOVA (Tukey post-hoc) were used to explore bivariate associations between financial burden, depression/anxiety risk, and demographic/clinical variables. Results: Participants were 91% non-Hispanic White, mean age = 57 years, SD= 15. 55% were currently receiving treatment (47% chemotherapy); 33% ever experienced metastatic disease. 22% reported annual income of ≤$40,000; 19% were not-employed due to disability. 13% spent $500+/month on out-of-pocket costs; 63% reported that a health care team member did not discuss cost of care with them. 36% did not know if they had enough assets to cover cancer treatment costs; 1 in 10 (11%) reported they could not meet monthly expenses. 1 in 3 reported (“quite a bit” to “very much”) worry about future financial problems resulting from illness/treatment (39%) and frustration that they cannot work or contribute as much as usual (34%). Greater financial burden was associated with lower income ( r= -.40, p= .001), greater out-of-pocket costs ( r= .24, p= .03), and not working due to disability F(5,58) = 3.84, p= .01. Among respondents, 38% were at risk for clinical depression; 44% for anxiety; greater financial burden was related to depression risk ( r = .51, p< .001) and anxiety risk ( r= .32, p= .012). Conclusions: Financial burden affects many people with ovarian cancer and is associated with poorer psychosocial outcomes. Ovarian cancer patients and survivors can benefit from access to comprehensive supportive care resources, including financial counseling. Cancer Support Community offers resources that may help, including a toll-free Helpline with a dedicated financial counselor. Future work will examine multivariate predictors of financial burden in ovarian cancer. Clinical trial information: NCT02333604 .
Impact of value frameworks on the magnitude of clinical benefit: Evaluating a decade of randomized trials for systemic therapy in solid malignancies.
Authors: Cusano Ellen , Wong Chelsea , Vaska Marcus , Nixon Nancy Alice , Karim Safiya , Abedin Tasnima , Tang Patricia A. , Heng Daniel Yick Chin , Ezeife Doreen Anuli
Published: May 2020

e19410

Background: In the era of rapid development of new, expensive cancer therapies, value frameworks were developed to quantify clinical benefit. We assessed the evolution of the magnitude of clinical benefit since the 2015 introduction of the ASCO and ESMO value frameworks. Methods: Randomized phase II and III clinical trials assessing systemic therapies for solid malignancies from January 2010 to July 2019 were evaluated. Study characteristics were recorded, and magnitude of clinical benefit (Δ) was calculated for the endpoints overall survival (OS), progression-free survival (PFS), response rate (RR), and quality of life (QoL). Multivariable analyses compared ΔOS, ΔPFS, and ΔRR in 2010-2014 [pre-value frameworks (PRE)] to 2015-2019 [post-value frameworks (POST)]. Results: In the 290 studies analyzed [60 (21%) PRE and 230 (79%) POST], the most common primary endpoint was PFS (46%), followed by OS (20%), RR (16%), and QoL (8%), with a non-significant increase in OS and decrease in RR as a primary endpoint in the POST era (Table). Studies evaluating immunotherapy and palliative therapy significantly increased POST [0 (0%) v 39 (17%), Fisher’s exact p<0.01 and 25 (42%) v 142 (62%), Chi squared p=0.01, respectively]. Studies reporting improvement in QoL doubled POST [3 (5%) v 22 (10%) Fisher’s exact p=0.56], however not statistically significant. Median ΔOS was significantly greater POST (N= 140 evaluable studies, 1.3 v -0.2 months, Wilcoxon p=0.005) but there was no significant difference in median ΔPFS or ΔRR. Multivariable analyses revealed significant improvement in ΔOS POST (OR 3.08, 95% CI 0.54-5.62, p=0.02) while adjusting for drug mechanism of action, line of therapy, disease setting, and primary endpoint. Conclusions: After the development of value frameworks, median OS improved minimally. The impact of value frameworks has yet to be fully realized in randomized clinical trials. Efforts to include endpoints shown to impact value, such as QoL, into clinical trials are warranted. [Table: see text]
Fluconazole vs. voriconazole prophylaxis for prevention of invasive fungal infections post haploidentical stem cell transplant.
Authors: Hamadeh Issam , Shahid Zainab , Chhabra Saurabh , Mendez Anjeanette , He Jiaxian , Butler Candace , Dodd Brandy
Published: May 2020

e19504

Background: IFIs are one of the most detrimental complications of profound and prolonged neutropenia post-allogeneic SCT. Prophylaxis with broad spectrum azole antifungals has become standard of care given favorable outcomes associated with their use in this setting. Nonetheless, the choice of antifungal agent varies between institutions due to absence of consensus guidelines in patients undergoing haploidentical SCT. Methods: Non-interventional retrospective study seeking to compare efficacy of fluconazole vs. voriconazole for prevention of IFI post haploidentical SCT for hematologic malignancies. SCT databases at two academic insitutions (one uses fluconazole and other uses voriconazole) were queried to identify patients who underwent allogeneic SCT from April 2012 until March 2018, and received prophlaxis with either voriconazole (group I) or fluconazole (group II). Patients with intent to start prophylaxis with fluconazole or voriconazole were included, even if antifungal agent was changed later. Primary endpoint was cumulative incidence of breakthrough IFIs (based on MSG criteria) on day +100 and +180. Fisher exact test was used to compare rates of breakthrough IFIs between two cohorts. Secondary endpoint was overal survival (OS). Kaplan Meiers analysis was performed to compare OS on day +180 and 1-year post SCT. Results: The cohort included 141 patients (group I: 75 and group II: 66). Percentage of patients who underwent transplant for leukemia was higher in group I compared to group II (77.3% vs. 56.1%, p < 0.001). A haploidentical SCT was performed in 62.7% of patients in group I compared to 100% in group II (p < 0.001). All patients received non-myeloablative conditioning. There was no statistically significant difference in rates of IFIs between two groups on day +100 (0% in I vs. 4.5% in II, p = 0.9) and +180 (1.4% vs. 4.6%, p = 0.2). A significant difference in OS was noted on day +180 and at 1-year in univariate analysis (Table). Conclusions: Our findings suggest that prophylactic use of either voriconazole or fluconazole after haploidentical SCT is associated with low rates of IFIs. However, survival data favored voriconazole over fluconazole. [Table: see text]
An ultrasensitive amplicon-based sequencing panel for noninvasive molecular testing of hematological malignancies using blood.
Authors: Cher Chae Yin , Lim Zi Yi , Tan Daryl , Mya Hae Tha , Mongkonsritragoon Wichean , Tan Min-Han , Choudhury Yukti
Published: May 2020

e19511

Background: Hematological malignancies, especially acute myeloid leukemia, myeloproliferative neoplasms, and myelodysplastic syndromes (MDS), present with distinct genomic alterations relevant to prognosis. Bone marrow (BM) is the primary sample source for genetic testing, but is obtained by an invasive biopsy procedure which carries risk of infection. An alternative non-invasive sample type to profile disease-relevant genomic alterations at diagnosis and subsequently, is desired for clinical decision making. An ultrasensitive sequencing panel was applied to peripheral blood (PB) as an alternative to BM, to demonstrate its utility for disease profiling and monitoring. Methods: A total of 27 pairs of matched PB and BM samples were obtained from patients with hematological malignancies including leukemia (n = 21), lymphoma (n = 4), multiple myeloma (n = 1) and MDS (n = 1). The sequencing panel covers 45 genes commonly mutated in myeloid and lymphoid malignancies. The panel is based on amplicon-sequencing and includes error correction for variant detection with allele frequency (VAF) as low as 0.1%. Optimized bioinformatics pipeline and in-house sequencing noise removal was used for variant selection and clonal analysis. Results: Complete concordance was seen for mutations detected in 23 of 27 patient-matched BM and PB paired samples. The likely cause of discordance in the other 4 pairs is attributable to mutations with low VAF ( < 0.5%). Overall, 91% of detected variants were concordant between PB and BM with strong correlation of VAFs (R = 0.9617). Serial testing trends correlated with stable disease with limited changes in VAFs (n = 2), and successful treatment response with rapidly falling VAFs (n = 5). In particular, 2 patients with FLT3-ITD and BCR-ABL1, respectively, identified at diagnosis had dramatic decrease in VAFs with respective targeted treatment. Conclusions: We report the utility of an ultrasensitive sequencing assay in PB with excellent concordance of mutations with BM, suggesting PB is a reliable alternative source for testing. In serial samples, the assay demonstrated value in treatment selection and response evaluation.
Treatment outcomes and healthcare resource utilization (HRU) among patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy in US community oncology setting.
Authors: Lyons Roger M. , Potluri Jalaja , Bui Cat , Choi Michelle E , Ma Esprit , Svensson Anders , Davies Kalatu , Annavarapu Srinivas , Kapustyan Tatyana
Published: May 2020

e19513

Background: Treatment options for AML patients ineligible for intensive chemotherapy are limited. This study aims to describe demographic and clinical characteristics, outcomes, and HCRU in this patient population. Methods: This was a retrospective observational study of patients aged > 60 years who received first-line (1L) treatment within 60 days of AML diagnosis between 1/1/2011 – 1/1/2018 and had > 2 visits at US Oncology Network (USON) clinics. Patients were followed until 6/30/2018, last visit, or death, whichever came first. Data were sourced from structured fields of the USON database and chart reviews. Patient characteristics and HRU were assessed using descriptive statistics while overall survival (OS), time-to-treatment failure (TTF), and progression-free survival (PFS) from 1L treatment initiation were assessed using the Kaplan-Meier method. Results: 378 patients were included with median age of 79 years; 62.7% were male, 29.3% had an ECOG score > 2, and 38.4% had poor cytogenetic risk profile. Most patients received 1L hypomethylating agent (HMA) monotherapy: azacitidine (AZA, 57.9%) or decitabine (DEC, 25.9%). Few patients received best supportive care only (7.1%) or other AML treatment (9.1%). Median (range) durations of 1L treatment among patients receiving AZA and DEC were 2.9 (0.0, 46.9) and 2.5 (0.1, 26.4) months, respectively. Median (95% CI) OS, TTF, and PFS in the AZA and DEC cohorts were 7.5 (5.7, 9.6) and 7.3 (4.8, 8.8) months, 3.4 (2.8, 4.4) and 3.7 (2.4, 5.2) months, and 6.7 (5.0, 8.0) and 5.7 (3.4, 7.4) months, respectively. Among patients receiving HMAs, 84.5% received at least one transfusion. Median number of red blood cell and platelet transfusions was 4.0. Hospitalization rates in the AZA and DEC cohorts were 79.9% and 83.7%; proportions with hospitalization > 2 days duration were 64.4% and 66.3%, respectively, with median (range) durations of 6.5 (3.0, 34.0) and 7.0 (3.0, 26.0) days, respectively. Conclusions: The low TTF and OS and high HRU in this real-world community oncology study indicates an unmet need to improve outcomes among AML patients ineligible for intensive chemotherapy. NCCN guidelines were updated since this study and future real-world studies are warranted to evaluate impact of novel therapies on treatment patterns and outcomes.
Evaluation of the differences between extramedullary and bone marrow relapse in adult acute lymphoblastic leukemia patients in terms of clinical features and survival outcomes.
Authors: Sayınalp Nilgun , Ciftciler Rafiye , Buyukasik Yahya , Haznedaroglu IC , Aksu Salih , Demiroglu Haluk , Goker Hakan , Ozcebe Osman
Published: May 2020

e19516

Background: Acute lymphoblastic leukemia (ALL) in adult patients is an uncommon and difficult-to-treat hematological malignancy that is characterized by excess lymphoblasts in the bone marrow (BM). Although many patients achieve remission with chemotherapy, relapse rates are high and survival outcomes in adults are worse than pediatric patients. With uncontrolled proliferation and accumulation of these lymphoblasts, normal hematopoiesis is suppressed and infiltrates various extramedullary (EM) regions. The aim of this study is to evaluate the difference between EM and BM relapse in adult ALL patients in terms of clinical features and survival outcomes. Methods: In this study, we retrospectively analyzed 108 patients who were diagnosed as ALL and treated in our tertiary care center between 2003 and 2019. Statistical analyses were performed using the SPSS software version 25. Results: The study included 108 patients, consisting of 64 males and 44 females with a median age of 30 (range: 17-79 years). The majority of cases were B-cell in origin; 87 (80.6%) patients had B-ALL and 21 (19.4%) had T-ALL. Median follow-up duration for all patients was 21.1 months (range: 0.49-158.7 months). In the follow-up, 28 patients (25.9%) were received allogeneic hematopoietic stem cell transplantation. A total of 27 (25%) patients relapsed during the follow-up period. In 15 (13.9%) of 27 patients, only BM relapse was observed. EM relapse was observed in 12 (11.1%) patients. EM localizations were identified: brain [n = 2, 1.8%], lung [n = 1, 0.92%], retroperitoneum region [n = 1, 0.92%], kidney [n = 2, 1.8%], breast [n = 1, 0.92%], vertebral column [n = 3, 2.7%], spleen [n = 1, 0.92%], and uvea [n = 1, 0.92%]. All of the patients relapsed with bone marrow were B-ALL. Five of the patients (41.7%) with EM relapse were T-ALL (p = 0.006). No significant difference was observed in terms of gender (p = 0.16) and age (p = 0.12) in patients with BM relapse and EM relapse. Median overall survival (OS) was 42.3 months (95% CI: 15.6-69.0) for patients with BM relapse and 32.8 months (95% CI: 20.0-45.5) for patients with EM relapse (p = 0.42). Conclusions: In conclusion, EM relapse is common in ALL patients. We observed that EM relapse is more frequent, especially in patients with T-ALL cell origin. no significant difference was observed in both groups in terms of OS. ALL patients should be carefully followed up in terms of EM relapses as well as bone marrow relapse.
Intestinal microbiota in patients with acute leukemia (AL) and allogeneic hematopoietics stem cell transplantation (allo-HSCT).
Authors: Acosta-Maldonado Brenda Lizeth , Vallejo-Leucona Fernando , Vaca-Paniagua Felipe , Rivera-Fong Liliana , Hernández-Urzúa Elizabeth , De La Garza Jaime G. , Valero-Saldana Luis Manuel , Venegas-Olvera Alinne , Lozano-Aguirre Luis , Velazquez Consuelo , Herrera Angel , Aguilar Jose Luis
Published: May 2020

e19518

Background: Microbiome is a challenging study area due to its influence on the multiple host functions. The majority of human-associated microbes reside within the colon. Our understanding about the complex interplay between host and environmental factors to shaping the microbiota is evolving rapidly AL is an unfavorable prognosis disease whose only cure possibility is the allo-HSCT. This procedure uses high doses of chemotherapy and multiple drugs such as antibiotics, antiviral, antifungals, and immunosuppressants that damage the mucous membranes and alter the intestinal microbiome balance. These events have been linked to bacterial resistance, relapse risk, Graft Versus Host Disease (GVHD), and poor Overall Survival (OS). The present study’s objective was to identify the intestinal microbiome bacteria groups during allo-HSCT and to evaluate their impact on patients outcome. Methods: Observational and prospective study was performed. Eleven patients with acute leukemia under alloHSCT and 11 health control (relatives) were enrolled. Gut faecal samples were collected in both groups; three for patients (at income day (ID), neutropenic period (N) and 30 days after discharge (+30D) and one in healthy donor (HD) at income day of their relatives. Bacterial 16S rRNA gene sequences were characterized by illumina and QUIIME 2. Biodiversity of microbiome was evaluated by OTUS, Shannon index and dominance. This proyect was supported by CONACyT. Results: We analyze 11 patients, 55% were male, with a median of 25 years-old at allo-HSCT. 7/10 received a HLA-identical and 4/10 an haploidentical HSCT. 82% had GVHD (I-IV), 1/11 died (two due to infections-GVHD and one of disease relapse). We analyzed 44 samples. There are no difference between healthy control group and income day patients’ samples. Statistical differences in the patients’ microbiome were identified among HSCT moments. According OTUS and Shannon Index the biodiversity decrease at neutropenia, and increase at day +30 outcome but it doesn’t represent a complete recovery. Greater bacterial dominance was observed in neutropenia period. (Table). 3/10 patients who died didn’t recovery biodiversity at day +30. Conclusions: Our results suggest that poor microbiome biodiversity recovery could be a worst prognostic [Table: see text]
Induction and maintenance for chronic myeloid leukemia-chronic phase: A novel treatment strategy.
Authors: Jain Aditi , Mahapatra Manoranjan , Seth Tulika , Irom Anil , Sazawal Sudha
Published: May 2020

e19526

Background: Imatinib remains the standard of care for CML-CP in many countries because of its affordability and safety with long term use. Given that upfront Nilotinib has higher rates of major molecular response and early deep responses predict long term responses, we hypothesized that upfront Nilotinib as induction followed by Imatinib maintenance may help to capitalize on the efficacy of Nilotinib without sacrificing the safety and efficacy of Imatinib. Methods: CML CP patients were divided into 3 groups at the time of diagnosis. Group 1 received Imatinib 400mg OD upfront, Group 2 and 3 received Nilotinib 300 mg BD for 1st 3 and 6 months respectively then switched over to Imatinib 400 OD. Quantitative real time PCR for BCR-ABL (RQ PCR for BCR-ABL) was done at 3, 6,12, 18, 24, 30, and 36 months to assess response. 3 early molecular responses were defined for analysis. EMR 1 was defined as Bcr-abl RQPCR < 10% at 3 months, EMR 2 as < 1% at 6 months and EMR 3 as < 0.1% at 6 months. Results: Patients on Nilotinib induction had deeper responses than patients on Imatinib at 3 and 6 months. However, subsequent molecular responses were similar in all 3 groups. The rates of Early Molecular responses were significantly better in the Nilotinib group compared to the Imatinib group. Significantly lesser patients in Group 1 had EMR 1 compared to Groups 2 and 3 [80.49% vs 100% vs 95.56%, p value 0.001]. Results were similar for EMR 2 and 3 [EMR 2: 34.15% vs 42.11% vs 60%, p value 0.017, EMR 3: 25.71% vs 25.53% vs 44.44%, p value Group 1 vs Group 3: 0.030]. TKI failure/progression rates were significantly better amongst patients who achieved EMR vs those who did not achieve EMR for EMR 2 and 3 but not EMR 1. For EMR 2, 42.68% who did not achieve EMR eventually had TKI failure compared to 18.03% of those who achieved EMR (p value 0.002). Similarly, 32.95% who failed to achieve EMR 3 progressed vs 11.9% of those who achieved EMR 3 (p value 0.011). 3 patients in group 1 and 1 patient in group 2 developed T315I mutation while none did in Group 3. Conclusions: The early advantage achieved with Nilotinib Induction was not sustained after switching to Imatinib maintenance. Nevertheless, target responses were still achieved and similar failure rates were present in all 3 groups. Patients who attained an EMR < 1 % at 3 months or < 0.1% at 6 months tend to have higher EFS and lower rates of TKI failure/progression irrespective of the treatment arm.
Factors other than sheer numbers of blood cells in circulation may be responsible for clinical presentations in chronic myeloid leukaemia.
Authors: Othieno-Abinya Nicolas Anthony , Odhiambo Andrew Oluoch , Ezzi Mohammed Shabbir , Oyiro Peter Omondi
Published: May 2020

e19527

Background: CML commonly presents with abdominal pain and swelling, and in up to about 50% of cases it is discovered incidentally due to abnormally elevated white blood cell (wbc) counts in circulation. Some present with bleeding tendency, others nusual presentations including hearing and visual loss whose pathogenesis is poorly understood also occur. Priapism presents rarely, attributed to hyperviscosity complicating wbc counts ≥ 250x109/litre. Nonspecific symptoms also present. We wanted to interrogate the link between baseline myeloid elements in circulation, bone marrow blasts, and BCR-ABL values with clinical manifestations. Methods: Patients attending the Glivec International Patient Assistance Clinic at the Nairobi Hospital had records prospectively collected, and analyzed. These included demographic profiles, physical examination, and laboratory values. Absolute, range, median and mean counts for wbcs, absolute neutrophil counts (ANC), platelets, haemoglobin and BCR-ABL values, were tested against each of the clinical presentations. Results: There were 583 patients, males 322 (55.2%) and females 261 (44.8); mean age 39.8 years. Commonest symptom was abdominal swelling in 235 cases (40.3%); 70 (12%) experienced abdominal pain. Priapism occurred in 4 males (1.2%), blindness and deafness in 8 patients (1.4%). Splenomegaly was more common among males than females; [Pearson Chi2 (1) = 5.9545, ( Pr = 0.015)]. Patients aged ≤ 20 years were more likely to be in heart failure, [Pearson Chi2 (3) = 8.8255,( Pr = 0.032)], leg swelling more in those with high platelet counts; [Ranksum test, (p = 0.023)]. Unclear presentation was more common in those with high wbc counts; [Ranksum test, (p = 0.015)]. Total wbc counts and BCR-ABL levels were higher among younger patients; [Kruskal-Wallis test (p = 0.036, and 0.025 respectively)]. Patients with leg swelling had lower BCR-ABL levels; [Ranksum test (p = 0.005)], those in heart failure had significantly higher BCR-ABL levels at baseline compared with the rest; [Ranksum test (p = 0.037)]. Patients with lymphadenopathy were more likely to have lower ANCs; [Ranksum test (p = 0.035)]. Conclusions: Clinical manifestations of CML cannot be explained merely by haematologic values. Complex biologic factors should be interrogated further.
Superior therapy response predictions for patients with myelodysplastic syndrome (MDS) using Cellworks Singula: MyCare-009-02.
Authors: Stein Anthony Selwyn , Watson Drew , Kapoor Shweta , Ghosh Roy Kunal Ghosh , Alam Aftab , Sahu Diwyanshu , Basu Kabya , Prakash Annapoorna , Ullal Yashaswini , Raju Karthik Sundara , Suseela Rakhi Purushothaman , Joseph Vishwas , Basu Sayani , Kumar Chandan , Mohapatra Subrat , Kumari Pallavi , Birajdar Shivgonda , Gopi Reshma , Mitra Upasana , Marcucci Guido
Published: May 2020

e19528

Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of MDS patients remains relatively poor. Therapy selection is often based on information considering only cytogenetics and single molecular aberrations and ignoring other patient-specific omics data that could potentially enable more effective treatments. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a more accurate predictor of patient-specific therapy response than PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 146 MDS patients aged 28 to 89 years (median 69) treated with PPT. Patient omics data was available from PubMed and TCGA. The accuracy of Singula was compared to that of PPT using McNemar’s test to account for the correlation between Singula and PPT. Multivariate logistic regression modeled complete response (CR) as a function of patient age, PPT, and Singula against any non-response (NR). Likelihood ratio tests were performed to further validate if Singula provides predictive information beyond PPT or patient age. Similar analyses were performed for overall survival (OS) using proportional hazards regression. Results: Singula was a better predictor for CR than PPT (McNemar’s χ2 = 42.0, p-value < 0.0001), with an overall accuracy of 73.3% (Exact 95% CI: 65.3%, 80.2%) compared to 37.7% (95% CI: 30.0%, 46.1%) for PPT. Singula exhibited a sensitivity and specificity of 90.9% (95% CI: 80.0%, 97.0%) and 62.6% (95% CI: 51.8%, 72.6%), respectively. In multivariate regression analysis, Singula (p < 0.0001) remained an independent predictor for CR after adjusting for patient age (p = 0.0759) and PPT (p = 0.0496). Singula provided alternative therapy selections for 17 of 53 true negative detected by Cellworks. Conclusions: Singula is a superior independent predictor for CR compared to PPT in MDS patients. The Singula report can also validate therapy selection, correctly identify non-responders to PPT and further provide alternative therapy selections.
Secondary myelodysplastic syndrome identified via next-generation sequencing in non-small cell lung cancer patients.
Authors: Feng Yongzhi , Tao Feng , Jiang Libin , Ni Dan , Zhang Jun , Wu Linxin , Shi Lin , Yu Genhua
Published: May 2020

e19531

Background: Chemotherapy and radiotherapy used in cancer treatment are associated with increased risk of secondary myelodysplastic syndrome (MDS). MDS is characterized with specific chromosomal abnormalities and genomic alterations in JAK2, KRAS, CBL, DNMT3A, TET2, IDH1/2, EVI1, RUNX1, GATA2, EZH2, ASXL1, SF3B1, U2AF1, SRSF2 and ZRSR2. Since next generation sequencing (NGS) techniques have been widely used for the detection of actionable genomic variation in solid tumor patients, analysis of NGS data for chromosomal abnormalities and gene mutations may be supplementary for diagnosis of secondary MDS. Methods: We retrospectively analyzed targeted NGS data of paired tumor and blood samples from patients with non-small cell lung cancer (NSCLC) for chromosomal abnormalities and gene mutations. Sequence panel covered whole exons of 381 genes associated with cancers. Sequence data were processed using a customized analysis pipeline designed to accurately detect multiple classes of genomic alterations in routine clinical specimens. All testing was done in a CLIA-certified, CAP-accredited laboratory. Clinical information of cases with chromosomal abnormalities was reviewed, including treatment for previous cancer, blood and bone marrow tests. Results: We found 4 cases carrying MDS associated chromosome abnormalities among 3523 NSCLC patients with the prevalence of0.1%. They were old (from 66 to 71 years old), and were more likely to be male (3 males and 1 females). All of 4 cases included common abnormalities associated with MDS like 5q-, 7q-, -7, +21. 3 cases had complex (≥3) abnormalities and 1 case had double abnormalities. Point mutations were identified in blood samples of 3 cases. Mutations in TP53 occurred in 3 cases, mutations in ASXL1, DNMT3A, FLT3 and CBL occurred in one case respectively. Among the 4 cases, 2 cases were confirmed as MDS by blood and bone marrow tests. Conclusions: We identified 4 MDS associated chromosomal abnormalities from 3523 NSCLC patients through analyzing NGS data. NGS techniques could serve as supplementary for diagnosis of secondary MDS. [Table: see text]
Quantifying unmeasured confounding in three epidemiological studies associating myelodysplastic syndromes (MDS) with cardiovascular disease (CVD).
Authors: Singh Abhay
Published: May 2020

e19532

Background: Confounding occurs when an investigator studies the effect of an exposure on the occurrence of an outcome, but in the process measures the effect of another factor (a confounding variable). Knowledge of possible causal pathways assists an investigator to minimize confounding, but despite utmost attempts, errors are frequent. To assess role of a possible confounder (smoking), data from 3 studies (1. Herrera at al. 2019 2. Goldberg et al. 2010 and 3. Brunner et al. 2017) associating MDS (exposure) with CVD (outcome) was used to conduct sensitivity analysis. Methods: 2 x 2 tables were constructed with data from 3 studies (part 2 of table below). A vector defining the proportion of confounder (smoking) among exposed [prop (Smoking+|MDS+)], unexposed [prop (Smoking+|MDS-)] and risk ratio associating smoking status with CVD (part 1) using historical data was deduced. Extracted data was added to online bias analysis tool ( https://sites.google.com/site/biasanalysis/ ) to calculate crude as well as mantel-haenszel (MH) relative risk (RR) adjusted for smoking. Results: RRs unadjusted for smoking status for studies 1, 2 and 3 were 1.31, 1.34 and 2.21, respectively, signifying increased risk of CVD in MDS patients (part 3). Upon adjustment for smoking status, MH-RR for MDS-CVD relationship was 0.95, 0.97 for studies 1 and 2 respectively, signifying no increased CVD risk and 1.59 for study 3 signifying increased CVD risk but lower upon adjustment. Conclusions: Making inference of MDS-CVD association without accounting for smoking status can blur effects and at times result in false associations. Given ambiguity in results from these 3 studies, further evidence is needed to better assess MDS-CVD relationship. A simple online tool allows estimating nonrandom errors, assess magnitude and direction of biases, and help clinicians/researchers quantify these biases for better interpretation of observational data in a time efficient manner. Other bias analyses for these studies will be presented. [Table: see text]
A real-world single-center retrospective study on efficacy and safety of pegylated interferon alpha-2a in patients with myeloproliferative neoplasm.
Authors: Ozcan Muhit , Koyun Derya , Cengiz Seval Guldane , Uslu Atilla , Kırcalı Ekin , Ozturk Cemaleddin , Civriz Bozdag Sinem , Toprak Selami Kocak , Topcuoglu Pervin , Arslan Onder , Ilhan Osman , Beksac Meral
Published: May 2020

e19536

Background: Pegylated forms of interferon (PEG-IFN) have a better pharmacologic profile than short-acting interferons, resulting in a more convenient less-frequent schedule of injections, less immunogenicity and possibly less toxicity. Several clinical studies of PEG-IFN-α-2a have reported promising results in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Herein, we present the outcomes of MPN patients treated with PEG-IFN-α-2a seen outside of a clinical trial setting at a single center. Methods: Thirty-five MPN Patients treated with PEG-IFN-α-2a between January 2014 and October 2019 were included this retrospective analyses. Therapeutic responses for ET and PV were calculated by the revised ELN/IWG-MRT criteria. Responses in myelofibrosis (MF) were calculated by both EUMNET and ELN/IWG-MRT criteria. Best responses over all cycles of treatment were assessed. Molecular data was limited to JAK V617F. Results: Twenty patients with ET, 13 with PV and two with MF were enrolled in this study. The median age at diagnosis was 47 years (range; 21-83 years). JAK2 V617F mutation was detected in 16 patients (45.7%). Overall, the majority of patients (62.9%) had received at least one prior cytoreductive therapy for underlying disease. Median starting dose of PEG-IFN-α-2a was 90 mcg/week via self injection (range: 45-135 mcg/w). Treatment duration was pursued for a median duration of 21.4 months (range: 1.2-109.8). In the PV/ET group 33 patients were evaluated and overall best response rate was 87.8% (CR in 15 pts and PR in 14 pts). In the MF group (n = 2); a PR was seen in one patient and CR in one patient. No vascular events occurred within the cohort while on therapy. Of the eight patients receiving at least phelebotomy per month, all patients became phelobotomy independent with therapy. Of the 20 ET patients, 12 patients (60%) had platelet normalization (< 450 x 109/L). Among all patients, fatigue (31.4%), muscle pain (20%) and depression (8.6%) were the most common adverse events (AEs). Any grade of hematological AEs was not seen with PEG-IFN-α-2a. Eleven patients discontinued therapy secondary to: treatment associated severe AEs in 8 patients, lack of response in two patients and pregnancy in one patient. No death was reported during the analyses period. Conclusions: Our results suggest that PEG-IFN-α-2a remains a viable treatment option especially for younger patients who want to avoid prolonged cytotoxic therapy.
Correlative study of disease activity in Langerhans cell histiocytosis.
Authors: Edwards Jeffrey Garnet , Jeng Michael Raymond
Published: May 2020

e19540

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia that primarily affects younger children, most often involving bone, skin, lung, lymph nodes, or liver. Current treatment for LCH includes chemotherapy and biologically targeted therapies. Given its clinical heterogeneity and low prevalence, decision-making regarding intervention relies on subjective evaluation of disease status, which is often dependent on provider experience. Thus, there is a need to identify biomarkers for disease recurrence and activity in patients with LCH. Methods: We conducted a retrospective cohort study including pediatric LCH patients (n = 48) ≤21 years of age with biopsy-proven diagnosis of LCH and ≥1 year of follow-up after diagnosis. Data regarding demographics, symptom history, organ system involvement, and laboratory values at different time points were extracted from the from patient medical records and entered into a REDCap Database. The primary outcome was recurrence status as measured by the end of the study period. Data were analyzed using Stata statistical analysis software. Results: In our cohort, the sample was 64.6% Male and 35.4% Female with a median age of 29 months at diagnosis. 68.1% of patients had single organ involvement while 31.9% exhibited multi-system involvement. 70.8% of our cohort received treatment with chemotherapy with an average initial treatment duration of 12.1 months. 27.1% of the cohort experienced recurrence by the time of chart review. Logistic regression of the demographic factors and lab values at diagnosis revealed a statistically significant association between multi-system involvement (OR: 3.94, p = 0.04), moderate or high central nervous system risk assessment (OR: 7.67, p = 0.03; OR: 5.75, p = 0.03) and likelihood of recurrence. Additionally, logistic regression analysis revealed that alkaline phosphatase level at the time of diagnosis was associated with a slightly decreased likelihood of recurrence (OR: 0.987, p = 0.02). Conclusions: These results reveal that in addition to the traditionally utilized inflammatory markers (Erythrocyte Sedimentation Rate, White Blood Cell and Platelet Count), Alkaline Phosphatase could be used as a predictor of disease activity for patients with LCH, especially for those with bone involvement. Moving forward, an increased sample size might reveal other correlative biomarkers that can predict disease activity, helping to more precisely manage LCH.
Leveraging real world data and AIML to inform smart patient care in oncology.
Authors: Zhou Li , Steen Rob , Lu Lynn
Published: May 2020

e20002

Background: Identifying optimal therapy options can help maximize treatment outcomes. Finding ways to help improve treatment decision is of great value to achieve better patient care. With the availability of robust patient real world data and the application of state of the art Artificial Intelligence and Machine Learning (AIML) technology, new opportunities have emerged for a broad spectrum of research needs from oncology R&D to commercialization. To illustrate the above advancements, this study identified patients diagnosed with CLL who may progress to next line of treatment in the near future (e.g. future 3 months). More importantly, we can identify treatment patterns which are more effective in treating different types of CLL patients. Methods: This study includes multiple steps which have already been analyzed for feasibility: 1. Collect CLL patients. IQVIA's real world data contains ~60,000 active CLL treated patients. ~2,000 patients have progressed line of treatment in 3 month. 2. Define patients into positive and negative cohorts based on those who have/have not advanced to line L2+. 3. Determine patient profiles based on treatment regimens, symptoms, lab tests, doctor visits, hospital visits, and co-morbidity, etc. 4. Select patient and treatment features to fit an AIML predictive model. 5. Test different algorithms to achieve best model results and validate model performance. 6. Score and classify CLL patients into high and low probability based on the predictive model. 7. Match patients based on feature importance and compare regimens between positive and negative cohort. Results: Model accuracy is above 90%. Top clinical features are calculated for each patient. Optimum treatment patterns between high and low probability patients are identified, with controlling patient key features. Conclusions: Conclusions from this study is expected to yield deeper insight into more tailored treatments by patient type. CLL patients started with oral therapy(targeting) have better response than other treatments.