tbuckley/cabot-search huggingface dataset:
ASC4REAL: Efficacy and tolerability comparison between ASCEMBL study, a phase 3 randomized clinical trial (RCT), and consolidated real-world (RW) experience with asciminib (ASC) in patients with CML beyond two TKIs.
Authors: Anchit Khanna, Hannah Small, Dhamend Lutchman, Peter Schofield
Journal: Journal of Clinical Oncology (2024)

e18519 Background: Despite advances in the management of chronic myeloid leukemia (CML), effective treatment options in later lines are limited. Treatment failure rates increase with each line of treatment and sequential tyrosine kinase inhibitor (TKI) therapy is associated with increased resistance. Importantly, almost all TKIs in the clinics target the ATP-binding site potentially resulting in off-target effects and long-term tolerability issues. Although data for ASC, a novel allosteric TKI targeting the myristoyl pocket, is emerging in the RW setting, low patient numbers in ASC RW studies hinders a robust comparison with the larger phase 3 RCT study. Methods: Post systematic literature search, data from 9 published or publicly presented RW studies was extracted. 319 CML patients that received ASC beyond 2 TKIs were included in this analysis. RW studies that had less than 10 patients were excluded. The results were then compared to estimates from the ASCEMBL study. Results: Compared to the RCT, RW studies showed similar or higher efficacy based on major molecular response (MMR) and deep molecular response (DMR) rates, achieved in shorter time. Rate of discontinuation of ASC was also lower in the RW setting. Similarly, some adverse events, specifically thrombocytopenia and arterial occlusive events (AOE) were lower, while some such as myalgia were higher in the RW setting when compared with the RCT. Conclusions: This analysis demonstrates ASC as an effective TKI for CML patients in the RW setting, supporting the results from the ASCEMBL RCT. [Table: see text]
Predictors of disseminated intravascular coagulation in patients with acute myeloid leukemia with severe sepsis and septic shock.
Authors: Saisree Reddy Adla Jala, Dhruvkumar Gadhiya, Yogeshwaree Ramphul, Madho Mal, Nayanika Tummala, Kanwar Bir Singh Dhaliwal, Hemamalini Sakthivel, Mehndi Dandwani, Kamleshun Ramphul, Suma Sri Chennapragada
Journal: Journal of Clinical Oncology (2024)

e18511 Background: Multiple pathophysiological pathways predispose Acute Myeloid Leukemia (AML) patients to Disseminated Intravascular Coagulation (DIC). As sepsis can also trigger DIC, we aim to evaluate the predictors of DIC among AML patients with severe sepsis and septic shock. Methods: We queried adults with a diagnosis of AML and severe sepsis with septic shock admitted between 2016 and 2020 in the United States via the National Inpatient Sample(NIS). Patients ages &lt;18 years were excluded from our sample. Multivariate regression models were used to estimate the impact of multiple factors on events of DIC among these patients. Results: Our sample consisted of 19545 cases of severe sepsis with septic shock in AML adults that matched our selection criteria. It included 1705(8.7%) patients who also experienced DIC during hospitalization. Several factors, such as medium (aOR 2.174, p&lt;0.01) and high frailty risk (aOR 1.788, p&lt;0.01, vs. Low frailty risk), history of nutritional anemia (aOR 1.580, p&lt;0.01), cirrhosis (aOR 2.316, p&lt;0.01), chronic kidney disease (CKD) (aOR 1.319, p&lt;0.01), systemic lupus erythematosus (SLE) (aOR 1.845, p=0.040), Females (vs. Males, aOR 1.169, p&lt;0.01), and patients covered by Medicaid (vs. Medicare, aOR 1.325, p&lt;0.01) showed higher odds of DIC. In addition, those ages ≥60 years were less likely to experience an event of DIC (aOR 0.699, p&lt;0.01), as DIC patients were younger (mean age 58.85 years vs. 62.43 years, p&lt;0.01). Patients with obesity (aOR 0.605, p&lt;0.01), smoking (aOR 0.772, p&lt;0.01), and cachexia (aOR 0.738, p=0.038) also showed fewer events of DIC. However, no racial differences were found between Blacks(aOR 0.928, p=0.404) or Hispanics (aOR 1.019, p=0.831)(vs. Whites). DIC patients who died were also older (mean age 59.99 years vs. 56.19 years, p&lt;0.01). Finally, we were also able to confirm that events of DIC led to poorer prognosis with a higher rate of all-cause mortality (70.1% vs. 47.6%, aOR 2.169, p&lt;0.01). Conclusions: Factors increasing the risk of DIC in patients with AML and severe sepsis with septic shock included anemia, cirrhosis, CKD, SLE, medium and high frailty risk, female sex, and Medicare insurance. While we noted lower odds of DIC among patients who are ≥60 years old, obese, cachectic, and smokers, further hospital-based studies to evaluate the severity of their illnesses along with other variables that could be analyzed via the NIS should be encouraged.
Clinicians' perspectives of barriers and facilitators of suicide screening in head and neck cancer care.
Authors: Nosayaba Osazuwa-Peters, Judith Mwobobia, Laura J. Fish, Margaret Falkovic, Revital Benvenisti, Walter T. Lee, Ross Brownson, Donald L. Rosenstein, David B. Goldston
Journal: Journal of Clinical Oncology (2024)

e18023 Background: Patients with head and neck cancer (HNC) face a heightened risk of suicide, surpassing rates in other cancers and the general population. Unfortunately, there are currently no suicide-specific clinical guidelines in oncology, and it is unclear what barriers and facilitators impact suicide screening initiatives in HNC care. This qualitative study explored experiences, barriers and facilitators of suicide screening and management of mental health concerns in a diverse group of HNC clinicians. Methods: We conducted qualitative interviews with 16 HNC clinicians at a single healthcare system, including head and neck surgeons, radiation oncologists, medical oncologists, and nurses/nurse practitioners/physician assistants. Interviews covered topics such as clinicians’ perspective of the impact of HNC on patients’ mental health, experience with suicide risk assessment, existing protocols, and overall experiences related to managing mental health concerns in patients with HNC. Using rapid analysis techniques, we identified common challenges, facilitators, and training needs. Results: Our study uncovered distinct barriers faced by HNC clinicians. Key themes included the notable absence of formal suicide and mental health training among HNC clinicians; critical gaps in clinician education and the lack of established protocols for appraising and managing mental health concerns, particularly those related to suicide risk. Other barriers identified included clinicians’ uncertainties in recognizing and addressing suicidal thoughts, limited familiarity with available screening tools, and insufficient resources for patient support. Some key facilitators also emerged, including longer clinic visit times, mental health discussions in interdisciplinary conferences, and greater accessibility of mental health services for comprehensive patient support. Conclusions: In this qualitative study, we observed important barriers in mental health support and service delivery for HNC patients, especially gaps in clinician training, and lack of knowledge of existing suicide-related protocols. Given the suicide burden in HNC, it is important to address these challenges and begin developing initiatives for clinician training and formalized protocols to enhance mental health care for HNC patients.
RNA expression-based risk stratification of de novo acute myeloid leukemia.
Authors: Donghyun Kim, Yeonhwa Yu
Journal: Journal of Clinical Oncology (2024)

e18503 Background: Prognostication of acute myeloid leukemia (AML) at initial diagnosis relies on the identification of certain underlying genetic abnormalities as proposed by the European LeukemiaNet (ELN) risk classification. However, AML is highly heterogenous at the molecular level and standard guidelines are often not straightforwardly applicable. In this study, we explored gene expression-based risk stratification strategies and found that FLT3 and NPM1 transcript level profiles can predict overall survival in de novo AML. Methods: The Cancer Genome Atlas AML (TCGA-LAML) project’s normalized RNA-Seq transcriptome profile (n=158) published in 2013 was analyzed with MATLAB software. "High” or “low” level of each gene was determined by the median RPKM of the cohort used as cutoff. P-values were obtained from Cox proportional hazards regression model. Results: The low-FLT3 level group was associated with superior median OS (mOS) compared to high-FLT3 group (24 vs. 16 months; p = 0.02), whereas high-NPM1 level group was associated with superior mOS compared to low-NPM1 group (26 vs. 12 months; p = 0.03). The mOS for high-FLT3/low-NPM1 and low-FLT3/high-NPM1 groups were 9 months and 27 months, respectively (p = 0.001). In high-FLT3/low-NPM1 and low-FLT3/high-NPM1 groups, composition of Cancer and Leukemia Group B (CALGB) cytogenetic risk category [favorable, intermediate, adverse] was [9%, 73%, 18%] and [32%, 49%, 19%], respectively; composition of French-American-British (FAB) classification [M0, M1, M2, M3, M4, M5, M6, M7] was [15%, 27%, 3%, 6%, 24%, 24%, 0%, 0%] and [3%, 14%, 41%, 19%, 22%, 0%, 0%, 3%], respectively; composition of FLT3/NPM1c mutations [ wt/wt, mut/wt, wt/mut, mut/mut, NOS] was [45%, 18%, 18%, 18%, 0%] and [61%, 14%, 7%, 14%, 2%], respectively. Conclusions: We demonstrate a de novo AML risk categorization method solely based on FLT3 and NPM1 RNA-Seq transcript levels. The mOS of high-FLT3/low-NPM1 group resembled that of ELN "adverse" risk group, whereas the mOS of low-FLT3/high-NPM1 group resembled that of ELN "favorable" risk group. High-FLT3/low-NPM1 group was composed of fewer "favorable” but more “intermediate” CALGB risk categories compared to low-FLT3/high-NPM1 group. Notably, considerably more FAB M0, M1 and M5 but fewer M2 and M3 classes were enriched in high-FLT3/low-NPM1 group compared to low-FLT3/high-NPM1 group. We also note approximately half of the cases analyzed were FLT3 and NPM1 wild-types and speculate FLT3 and NPM1 transcript profiles may represent a global oncogenic state regardless of the underlying FLT3 or NPM1 mutations. This is also supported by the previously reported FLT3 mutation-like transcriptomic profiles observed in FLT3 wild-type AML cases 1) . Reference: 1) Mosquera Orgueira A, et al. Gene expression profiling identifies FLT3 mutation-like cases in wild-type FLT3 acute myeloid leukemia. PLoS One. 2021 Feb 16;16(2):e0247093
In-hospital outcomes of patients with myelodysplastic syndromes and rheumatic heart disease: A National Inpatient Sample study (2018-2020).
Authors: Rabia Iqbal, Mrunanjali Gaddam, Ahmad Taimoor Bajwa, Ana Colon Ramos, Samridhi Sinha, Surbhi Singh, Surbhi Singh, Jincy Clement
Journal: Journal of Clinical Oncology (2024)

e18525 Background: Autoimmune conditions are relatively uncommon in patients with Myelodysplastic syndromes (MDS), with only a small proportion of patients affected. Among these autoimmune conditions, rheumatic heart disease (RHD) is the most commonly associated with MDS. Very few cases have been reported in literature that show the impact of RHD on patients diagnosed with MDS. In this study, we aimed to investigate the impact of RHD on the patients with myelodysplastic syndrome who were admitted in hospitals from 2018-2020. Methods: We utilized National Inpatient Sample (NIS) 2018-2020 to identify hospitalizations of patients with Myelodysplastic syndromes with a secondary diagnosis of Rheumatic heart disease. The primary outcomes examined were In-patient mortality and average length of stay, All the patients with MDS were divided into two cohorts based on the presence of rheumatic heart disease. Multivariable regression analyses were conducted, taking into account demographics, hospital-level characteristics, and pertinent comorbidities as adjusting factors. Results: Using the NIS dataset from 2018 to 2020, we identified 222,364 patients admitted with MDS during this period. Among them, 4.57% (10,162 patients) also had a diagnosis of rheumatic heart disease (RHD). The average age of patients with MDS and RHD was 80 years. Among these patients, 50.1% were male and 49.9% were female. The mortality rate among patients admitted with MDS and coexisting RHD was 7.7%. Multivariate regression analysis indicated that the presence of RHD increased the likelihood of mortality with an odds ratio (OR) of 1.2 (95% confidence interval [CI]: 1.0-1.4, p-value &lt;0.05). Additionally, RHD was associated with a higher incidence of arrhythmias (OR: 2.9) and congestive heart failure (OR: 5.0) among MDS patients. The total hospital charges were more in patients with RHD than those without RHD ($80108 vs $82843). However, there was no significant difference in the length of stay (LOS) between patients with MDS alone and those with MDS and RHD. Conclusions: Rheumatic heart disease (RHD) cases in patients with MDS are rare in clinical practice, leading to uncertainty regarding the effects of RHD on admitted MDS patients. Our study sheds light on the influence of RHD on mortality and other outcomes in this patient population. The efficacy of timely RHD treatment in reducing mortality and improving outcomes among hospitalized MDS patients remains to be verified in future investigations. [Table: see text]
Prognostic impact of <i>caspase-8</i> mutation in oral cavity squamous cell carcinoma: A real-world cohort study.
Authors: Hsueh-Ju Lu, Ming-Fang Wu, Sung-Fa Yang
Journal: Journal of Clinical Oncology (2024)

e18029 Background: Identifying the drive genes and inhibiting its significant signals were persistently the main concept in cancer treatment. However, for oral cavity squamous cell carcinoma (OCSCC), the most influential genes for overall survival (OS) remain unclear. Methods: A total of 120 OCSCC patients, with corresponding pathologic specimens at initial diagnosis, were collected in Taiwan. After excluding eligible patients, 95 patients were enrolled for analysis. Whole-exome sequencing was done and the prognostic impact of each gene was analyzed. The Cancer Genome Atlas (TCGA) database was used to validate. Results: The incidences of caspase-8 mutation were 22.1% and 10.9% in the Taiwan and TCGA cohort, respectively. In the Taiwan cohort, caspase-8 mutation was the most significant independent for OS with an adjusted hazard ratio (HR) [95% confidence interval (CI)]: 3.83[1.84-7.99]). It was validated by the TCGA database (HR [95% CI]: 1.51[1.00-2.29]). The 5-year OSs of the patients with or without caspase-8 mutation were 38.1% vs. 75.3% ( P &lt; 0.001) (HR [95% CI]: 3.264[1.645-6.438]) in the Taiwan cohort, and 26.1% vs. 49.0% ( P = 0.048) (1.513[1.001-2.288]) in the TCGA cohorts, respectively. Caspase-8 mutation was also individually associated with poor prognosis for TNM stage I/II/III/IV, respectively. L81F, R127*, R472*, R494*, S174*, and T528I were the intersected point mutations of caspase-8. Most of these intersected point mutations were pathologic/likely pathologic variants in the published bioinformatic databases. Conclusions: In conclusion, caspase-8 mutation was the most significant genetic alteration impacting prognosis. Novel agent development could be considered for this candidate.
Timing of allogeneic hematopoietic cell transplantation for myelofibrosis and other myeloproliferative neoplasms.
Authors: Joshua S. Mercer, Claire I. Bradbury, Samantha M. Thomas, Sendhilnathan Ramalingam, Cristina Gasparetto, Taewoong Choi, Anthony D. Sung, Stefanie Sarantopoulos, Gwynn Douglas Long, Edwin Alyea, Mitchell E. Horwitz, Nelson Jen An Chao, Sanghee Hong
Journal: Journal of Clinical Oncology (2024)

e18517 Background: Myeloproliferative neoplasms (MPN) and myelodysplastic syndrome (MDS)/MPN overlap syndromes are rare hematopoietic malignancies in which allogeneic hematopoietic cell transplantation (HCT) is the only treatment with curative potential. Even for higher risk patients, the optimal timing for HCT is largely unknown. We interrogated HCT outcomes of myelofibrosis (MF) and the rest of MPN, MDS/MPN overlap based on the timing of HCT from diagnosis (Dx) to help oncologists determine the optimal timing to refer patients for HCT. Methods: This retrospective, single-center study obtained data from our HCT database. We included adult (&gt;18 years; y) patients who received their first allogeneic HCT between 2015 and 2022 for initial Dx of MPN or MDS/MPN overlap. We included all donor types and graft sources. Analysis was separated by MF vs. others (other MPN and MDS/MPN) to account for fibrotic vs proliferative nature of disease progression and sample size. The primary variable was the time from Dx to HCT. The primary endpoint was overall survival (OS) from HCT. Secondary endpoints were progression free survival (PFS) and non-relapse mortality (NRM) from HCT. Results: 46 patients (n=27 for MF, n=19 for others) were included. 59% were male (56% for MF, 63% for others). The median age at HCT for MF was 57y (range 45-72) and for others was 63y (32-75). For patients with MF and others, 85% and 84% received myeloablative conditioning, respectively. In the MF group, all patients had PBSC grafts and 37% of grafts were from match-related donors; in the others group, 89% had PBSC grafts (11% had BM grafts) and 53% of grafts were from match-related donors. The median time from Dx to HCT for patients with MF was 28 months (m; range 4-166) and for others was 11m (2-423). In the MF group, those whose HCT &lt;1y from Dx had improved OS (Table) and PFS (1y, 83.3% vs. 53.3%, p=0.031) compared to HCT ≥1y after Dx. However, no differences were found in OS or PFS for &lt;6m vs. &gt;6m from Dx to HCT. No differences in OS/PFS were seen based on the timing of HCT in the others group. Conclusions: Patients with MF, but not with other MPN or MDS/MPN, who received allogenic HCT &lt;1y from Dx had significantly improved OS and PFS. Our results suggest that early referral to HCT after confirmation of marrow fibrosis for higher risk MF may influence HCT outcomes positively. However, lack of improvement in OS/PFS at 6m suggests that addressing individual risks and initiating appropriate therapies for MF first may more effectively balance risks of post-HCT complication with disease progression. Additional studies investigating timing of HCT will help oncologists to direct management of MPN and MDS/MPN overlap. [Table: see text]
A propensity score–matched comparison of cytoreductive strategies in patients with acute myeloid leukemia presenting with hyperleukocytosis.
Authors: George Avetian, Thuy Ho, Hyun Lee, Ian Michael Bouligny, Keri Renee Maher
Journal: Journal of Clinical Oncology (2024)

e18509 Background: Hyperleukocytosis (white blood cell (WBC) count greater than 100x10 9 ), which may lead to the clinical entity of leukostasis, is a hematologic emergency present at diagnosis in 18% of patients with acute myeloid leukemia (AML). There is controversy regarding the appropriate cytoreductive strategy, which may include cytoreductive chemotherapy, hydroxyurea, and/or leukapheresis. The American society for apheresis (ASFA) released guidelines in 2023 making leukapheresis a Category III recommendation, however significant heterogeneity and methodologic flaws exist in the evidence used to make these recommendations. Methods: Retrospective analysis of 58 patients at Massey Comprehensive Cancer Center between 2017 and 2023 who received either hydroxyurea alone (n=35) or both hydroxyurea and leukapheresis (n=23) for hyperleukocytosis at time of presentation for AML diagnosis was performed. Baseline characteristics including age, sex, Charlson Comorbidity Index (CCI), European LeukemiaNet (ELN) risk stratification, and WBC count prior to cytoreduction were collected. Comparisons of complete remission rates (CR/CRi), 30- and 60-day mortality, median overall survival (OS), and rates of therapy-induced tumor lysis syndrome (TLS) and disseminated intravascular coagulation (DIC) were analyzed using Kaplan-Meier, Fisher’s exact, Mann-Whitney tests, respectively on a propensity score matched cohort to account for differing initial WBC counts between the treatment groups. Results: PSM was used to match presenting WBC counts between the two cohorts. Other baseline characteristics including median age (65y v. 60y), median CCI (5 v. 4), ELN adverse risk rate (31.53% v. 26.1%) did not differ after PSM. No significant difference was found between the hydroxyurea group compared to the hydroxyurea and leukapheresis group, respectively, when analyzing for rate of CR/CRi (36.5% v. 43.5%), 30-day mortality (10.5% v. 17.3%), 60-day mortality (10.5% v. 34.8%), median OS (7.77 mo. v. 8.07 mo.), or rates of DIC (10.5% vs. 8.7%) and therapy induced TLS (0% v. 0%). Conclusions: Patients who received hydroxyurea alone had similar outcomes when compared to the combined treatment group with respect to median OS, CR/CRi, and mortality rates. These results are notable given that leukapheresis is not available at many medical centers and is a resource-heavy procedure, and especially so in light of new ASFA guideline changes. However, these results reflect the laboratory entity of hyperleukocytosis rather than the clinical entity of leukostasis. Further work is ongoing to assess impact of cytoreductive strategies in leukostasis in AML, and among different cytogenetic and molecular subtypes. Decisions for leukapheresis or other cytoreductive strategies should be made on a case-by-case decision at an experienced center when possible.
Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: A retrospective multi-center study by the Turkish Oncology Group (TOG).
Authors: Arif Akyildiz, Deniz Can Guven, Baris Koksal, Beliz Bahar Karaoğlan, Derya Kivrak Salim, Osman Sütcüoğlu, Mert Erciyestepe, Ozkan Alan, Hakan Taban, Nilgun Yildirim, Teoman Sakalar, Dogan Yazilitas, Rashad Ismayilov, Sercan On, Ferit Aslan, Nebi Serkan Demirci, Yasemin Kemal, Omer Diker, Ibrahim Halil Gullu, Sercan Aksoy
Journal: Journal of Clinical Oncology (2024)

e18004 Background: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. The prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. Methods: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 22 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. Results: The median follow-up duration was 7.5 months (3-66.1 months). Overall survival (OS) and progression-free survival (PFS) were determined to be 11.8 and 3.8 months, respectively. Nivolumab exhibited clinical responses, yielding an objective response rate (ORR) of 29.9% and a disease control rate (DCR) of 55.7%. Safety assessments consistently revealed a well-tolerated profile, with no reported instances of treatment discontinuation or mortality attributed to adverse side effects. Notably, several factors, including performance status, neutrophil-to-lymphocyte ratio, tumor location, and p16 positivity, emerged as prognostic indicators significantly associated with OS. Conclusions: Nivolumab is an effective and safe treatment option for patient with recurrent or metastatic non-nasopharyngeal HNC in real-world setting. [Table: see text]