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  • 1
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3159-3159
    Abstract: Background Atypical HUS (aHUS) is a rare thrombotic microangiopathy (TMA) caused by complement dysregulation. Eculizumab is a humanized monoclonal antibody targeting against complement factor C5. Ravulizumab, a longer acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for treatment of aHUS in 2019. Here we describe the clinical presentation, laboratory, genetic profile, treatment along with long-term sequelae of patients diagnosed with aHUS. The outcomes of restrictive use of eculizumab and the use of ravulizumab were also studied. Materials and Methods We conducted a single center retrospective cohort study, searching electronic medical records of patients diagnosed and treated for aHUS at University of Arkansas for Medical Sciences, from January 1, 2013 to January 31, 2021, after IRB approval. Inclusion criteria :1) Presence of microangiopathic hemolytic anemia (MAHA) with thrombocytopenia 2) ADAMTS13 activity & gt; 10 % 3) Age & gt; 18. Exclusion criteria: 1) Age & lt; 18 years 2) TMA associated with hemolytic uremic syndrome, scleroderma renal crises, anti-phospholipid syndrome. Results Seventeen patients meeting the inclusion criteria were enrolled in the study. The mean age at diagnosis was 47.4 ± 17.9 years. Most of the patients were Caucasians (n=10, 58%) and females (n= 14, 82%). All the patients except one had acute kidney injury (AKI) at presentation (n=16, 94.1%), the most frequent extra-renal presentation was CNS involvement -seizures, confusion and altered mental status (n= 7, 41.2 %) followed by Gastrointestinal- non-bloody diarrhea, nausea and vomiting (n=5, 29.4 %) [Figure 1]. Lab investigations are described in [Table 1] . Complement genetic testing was done in 100% of study population. Factor H related genes 1/3 (CFHR1/3) and complement factor H (CFH) were the most commonly found pathogenic mutations [Table 2]. In this study, pregnancy and infection (n= 4, 23.5% each) were identified as the most common triggers [Figure 2] . For two of the patients, it was the first pregnancy and for the other two, it was their second and third pregnancies. They presented at the second, sixth, and sixteenth week postpartum respectively. Eleven (64.70%) patients developed chronic kidney disease (CKD) with six (35.29%) patients progressing to end stage renal disease (ESRD). Two (11.76 %) pregnant patients developed cardiomyopathy, two (11.76%) patients developed pulmonary complications (pneumonia and pulmonary hypertension) and three (17.64%) patients developed epilepsy. All the postpartum females in our study were able to breastfeed while on eculizumab with no long-term complications in the neonates. One patient had two subsequent deliveries with no ante, intra, or post-partum consequences or repeated triggers of aHUS. Fourteen patients (82.3%) received therapeutic plasma exchange, four (23.5%) patients received iv methyl prednisone (1mg/kg) and two (11.7%) patients received IVIg prior to initiating eculizumab. Over time, five (29.41%) patients opted to completely stop drug therapy and four patients (23.52%) chose to shift to ravulizumab because of the ease of treatment duration (every 8 weeks rather than every 2 weeks for eculizumab). All these nine patients remained in remission with stable hematologic and renal parameters on subsequent follow-ups [Table 3]. Three patients (17.6 % mortality) died in our study due to causes unrelated to aHUS. Conclusions: The clinical diagnosis of atypical HUS can be challenging especially with extra-renal manifestations. Females were four times more affected than males. PCMs were present in 11 patients. Early diagnosis and treatment with C5 inhibitors improves morbidity and mortality. The decision to discontinue or switch eculizumab to ravulizumab will likely decrease healthcare costs and improve patient compliance but should be based on disease severity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1629-1629
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1629-1629
    Abstract: BACKGROUND Heavy chain diseases (HCDs) are B-cell neoplasms characterised by production of monoclonal (M) protein consisting only of immunoglobulin heavy chain without a bound light chain. Three types have been recognized- IgA alpha HCD (most common, a form of extra nodal marginal zone lymphoma of mucosal associated lymphoid tissue aka immunoproliferative small intestinal disease [IPSID], Mediterranean lymphoma or Seligmann disease] , IgG gamma HCD (aka Franklin's disease, variant of lymphoplasmacytic lymphoma) and IgM mu HCD (rarest, resembles chronic lymphocytic leukemia). Limited data is available regarding the epidemiology, survival patterns, and incidence of second primary malignancies in patients with HCD in the Unites States. MATERIALS AND METHODS We performed a retrospective analysis using SEER* stat version 8.3.9 statistical software and November 2020 submission of SEER 18 registry which covers ~ 27.8 % of US population based on the 2010 census. We identified all cases & gt; 1 years old diagnosed with Heavy chain disease between 2000 and 2018 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9762/3. We analyzed survival using Kaplan- Meier method, and MP-SIR session was used to calculate the risk of second primary malignancy. RESULTS A total of 64 cases of HCD were identified. Most common primary sites of involvement were bone marrow (82.8%), lymph nodes (9.3%), GI tract (3.1%), others (4.6%)- spleen, blood and vertebral column. The crude, age-adjusted to 2000 US standard population and age-specific incidence rate of HCD in the United States is & lt; 1/100,000 respectively. The median age at diagnosis is 68 years with incidence in males being about 1.3 times that of females. Bimodal age distribution was observed, with peak incidence between ages 60-64 and 75-79 [Figure 1]. In our entire cohort, 82.8% (n=53) patients were Caucasians, 15.6 % (n=10) patients were African Americans, and 1.5% (n=1) patients were American Indian/Alaska Native. Among Caucasians, 56.6% (n=30) patients were males, and 43.3% (n=23) patients were females. Between 2000-2018, the maximum cases (n=7 each) were diagnosed in the year 2002 and 2008 [Figure 2] The median overall survival for the entire cohort was 48 months (95% CI: 35- 61). Overall survival rates of all ages, sex and race at 1 year, 2 year and 5 years were found to be 86.1%, 71.4%, 57.8% respectively. OS at 5 years declines after 70 years .Patients with HCD are at risk of developing subsequent solid and haematological malignancies within 5 years of diagnosis. 9 (14 %) cases developed SPMs: urinary bladder (n=1), lung and bronchus (n=2), Hodgkin-nodal (n=1), Non-Hodgkin Lymphoma -extra nodal (n=1), GI cancers [stomach (n=1), esophagus (n=1) and ascending colon (n=1)], miscellaneous (n=1). [Figure 4] . The mean follow-up duration for new SPM was 51 months. Overall, 39 patients died: 3 (4%) from miscellaneous malignant cancer and 11 (17%) patients from haematological malignancy; the most common being Non-Hodgkin lymphoma (n=8), followed by Hodgkin lymphoma (n=1), Multiple myeloma (n=1) and leukemia (n=1). CONCLUSIONS HCD is an extremely rare haematological malignancy. The incidence of HCD is proportionately higher among Caucasians as compared to other races, with no reported case among Asian or Pacific Islanders. Among Caucasians, males and females have approximately equal risk of acquiring HCD. Most patient die because of their primary haematological malignancy. We recommend close follow-up for at least the first 5 years after initial diagnosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4857-4857
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4857-4857
    Abstract: Introduction The overall impact of morbidity related to sickle cell disease (SCD) is enormous due to decreased quality of life, high health care utilization and immense financial strain on the patients and health care system. Patients with SCD have also been found have high hospital readmission rates compared to other medical conditions, further leading to increased health care burden. The objective of this study was to explore the common reasons, healthcare utilization and identify modifiable factors associated with 30-day readmission in patients with SCD using the most recently available national data in the United States. Methods Cohort selection. 2016 Nationwide Readmission Database (NRD) from the Healthcare Cost and Utilization Project (HCUP) by the Agency for Healthcare Research and Quality (AHRQ) was queried for analysis. NRD captures discharge data from 22 states, representing about 50% of all hospitalizations in the United States. National estimates can be produced by using sampling weights provided by the NRD. Patients with SCD were identified by using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code D57. Patients younger than 18 years were excluded. Readmission was defined as any admission within 30 days of index hospitalization discharge. Statistical Analysis. Sampling weights were used throughout all calculations, facilitating appropriate national projections. Percentages in all figures reflect national estimates. Chi-square test and Student's t-test were used for univariate analysis. Multivariable logistic regression analysis was done to determine independent predictors of 30-day readmission in patients with SCD. Data analyses was performed using SAS v9.4 (SAS Institute, Cary, NC). Results In a total of 83,692 hospitalizations for SCD in 2016, 15,880 (18.9%) had at least one 30-day readmission and 40% of the readmissions occurred within the first two weeks of discharge. The most common reason for 30-day readmission was due to complications of SCD (29.8%) with sickle-cell pain crisis (18.4%) being the most frequent one. The other common causes for readmission were sepsis (10.3%), cardiac related (9.7%), respiratory failure (6.2%), renal failure (4.3%) and mood related (4.04%). Female sex (P 〈 0.001), younger age (p 〈 0.01) and patients with public insurance (P 〈 .001) were more likely to be readmitted. Multivariable logistic regression analysis showed age 31-45 years (OR 1.28, 95% CI 1.16 - 1.40, P 〈 0.01), alcohol abuse (OR 1.39, 95% CI 1.17 - 1.66, P 〈 0.001), opioid abuse (OR 2.66, 95% CI 2.34 - 3.02, P 〈 0.0001), depression (OR: 1.59, 95% CI 1.45 - 1.73, P 〈 0.01), substance abuse (OR: 1.35, 95% CI 1.21 -1.50, P 〈 0.001), tobacco use (OR: 1.35, 95% CI 1.24 - 1.46, P 〈 0.01), heart failure (OR: 1.81, 95% CI 1.66 - 1.97, P 〈 0.002), COPD (OR: 1.74, 95% CI 1.55 - 1.96, P 〈 0.03) were significantly associated with 30-day readmission while adjusting other co-morbidities. The mean cost of readmission was an additional $39,259 (±182). Conclusion This study showed that the 30-day readmission rate in patients with SCD in 2016 has decreased to less than 20% compared to previously published rates (31.9%, Elixhauser A, 2013). While this decrease in readmission rate is encouraging, further studies are needed to investigate the reasons for this trend. Several modifiable risk factors were identified in this study such as alcohol, tobacco, opioid, substance abuse and depression which can be addressed to potentially bring down the readmission rate further and improve patient care. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 4
    Online Resource
    Online Resource
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2404-2404
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2404-2404
    Abstract: Introduction Disseminated Intravascular Coagulation (DIC) is a systemic coagulopathy which leads to widespread thrombosis and hemorrhage and ultimately results in multiorgan dysfunction. DIC usually occurs as a complication of illnesses like severe sepsis, malignancies, trauma, acute pancreatitis, burns, and obstetrical complications. The prognosis and mortality of DIC depend on the etiology, however, the mortality of DIC is known to be on the higher side. The aim of the study is to analyze if gender, race, regional differences have any association with the mortality of hospitalized patients with DIC. Method The National Inpatient Sample database from the Healthcare Cost and Utilization Project (HCUP) for the year 2016 was queried for data. We identified hospital admissions for DIC with the International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code D65. The data was analyzed with STATA 16.0 version and univariate and multivariate analysis were performed. We studied the characteristics of all such hospitalizations for the year 2016 and the factors associated with the in-hospital mortality rate (MR) of DIC. We used length of stay, cost of stay as an outcome to determine if gender, race, and location play a role in the mortality. Results A total of 8704 admissions were identified with a diagnosis of DIC during the year 2016. The mean age for admission was found to be 56.48± 0.22. The percentage of admissions in females and males did not have a notable difference (50.57% vs 49.43%). The disease specific MR for DIC was 47.7%. Admission during weekend vs weekdays did not carry a statistically significant difference in terms of MR. Females with DIC were less likely to die in the hospital when compared to males with DIC (OR= 0.906, CI 0.82 - 0.99, p= 0.031). Interestingly, African Americans (AA) with DIC admissions were found to have 24% more risk of dying when compared to Caucasians admitted with DIC (OR= 1.24, CI 1.10 - 1.39, P= 0.00), Native Americans (NA) has 67% more risk of dying when compared to Caucasians (OR= 1.67, CI 1.03 - 2.69, p= 0.035). The mortality rate of NA, AA, Caucasians with DIC was found to be 57%, 52%, 47% respectively. The MR was found to be highest in hospitals of the northeast region (52%), then hospitals in the south (47%), followed by west and mid-west (46%), p= 0.000. Patients admitted to west and mid-west were 24% less likely to die when compared to patients admitted to northeast region hospitals (OR= 0.76, p= 0.001). The average length of stay and cost of stay were also less in west and mid-west regions when compared to north east. The difference in outcomes persisted after adjusting for age, gender, race, hospital division, co-morbid conditions. Conclusion Our study demonstrated that African Americans and Native Americans with DIC have high risk of dying in the hospital. Also, there exists a difference between the mortality rate, length and cost of stay among different regions in the United States. More research is needed to elucidate the factors that might be impacting the location-based variation in mortality. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 5
    In: The Permanente Journal, The Permanente Federation, Vol. 24, No. 5 ( 2020-12)
    Type of Medium: Online Resource
    ISSN: 1552-5767 , 1552-5775
    Language: English
    Publisher: The Permanente Federation
    Publication Date: 2020
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  • 6
    In: Cancers, MDPI AG, Vol. 14, No. 6 ( 2022-03-10), p. 1428-
    Abstract: Therapeutic advancements in neuroendocrine tumors (NETs) have improved survival outcomes. This study aims to review the impact of the current therapeutics on health-related quality of life (HRQoL) in NET patients. A literature review was performed utilizing PubMed, The Cochrane Library, and EMBASE, using the keywords “Carcinoid”, “Neuroendocrine tumor”, “NET”, “Quality of life”, “Chemotherapy”, “Chemoembolization”, “Radiofrequency ablation”, “Peptide receptor radionucleotide therapy”, “PRRT”, “Surgery”, “Everolimus”, “Octreotide”, “Lanreotide”, “Sunitinib”, and “Somatostatin analog”. Letters, editorials, narrative reviews, case reports, and studies not in English were excluded. Out of 2375 publications, 61 studies met our inclusion criteria. The commonly used instruments were EORTC QLQ-C30, FACT G, and EORTC- QLQ GI.NET-21. HRQoL was assessed in all pivotal trials that led to approvals of systemic therapies. All systemic therapies showed no worsening in HRQoL. The NETTER-1 study was the only study to show a statistically significant improvement in HRQoL in several domains. The trial examining sunitinib versus placebo in pancreatic NETs showed no change in QoL, except for worsening of diarrhea. In addition to clinical outcomes, patient-reported outcomes are a key element in making appropriate treatment decisions. HRQoL data should be readily provided to patients to assist in shared decision-making.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 7
    In: Cancers, MDPI AG, Vol. 15, No. 17 ( 2023-08-25), p. 4264-
    Abstract: Background: The interaction between HER2-low expression, oncotype recurrence score (RS), and their influence on the prognosis of HR+/HER2- breast cancer (BC) is not very well studied. Methods: We conducted a retrospective cohort study of patients diagnosed with resectable HER2-low and HER2-zero BC from the National Cancer Database. The primary outcome was overall survival (OS), and the association of RS with the clinical outcomes in HR+/HER2- BC was analyzed as an exploratory endpoint. Results: The distribution of RS was comparable between HER2-low and HER2-zero groups; however, the RSs of HER2-low tumors were more likely to be 16–25. Women with HER2-low tumors had longer 5-year OS than women with HER2-zero tumors in the HR-negative (84.3% vs. 83.9%; p 〈 0.001, HR: 0.87 (0.84–0.90), p 〈 0.001) but not in the HR-positive group (94.0% vs. 94.0%; p = 0.38, HR: 0.97 (0.95–0.99), p = 0.01). The survival advantage was observed in patients who received adjuvant/neoadjuvant chemotherapy (p-interaction (chemo vs. no chemo) 〈 0.001). Among those who received adjuvant chemotherapy in the group with higher RSs (26–100), those with HER2-low BC had higher 5-year OS than HER2-zero BC. Conclusions: Resectable HER2-low BC had a better prognosis than HER2-zero BC. Among those who received adjuvant chemotherapy in the higher oncotype RS group, those with HER2-low tumors had better survival.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 530-530
    Abstract: 530 Background: Sarcomatoid bladder cancer is an extremely rare and aggressive histological variant with poor prognosis and limited consensus regarding its management given rarity and lack of high-quality data. Radical cystectomy (RC) is the mainstay of treatment in muscle-invasive disease and adjuvant therapy is often offered to eligible patients with high-risk features. Data regarding the role of neoadjuvant chemotherapy (NAC) for this variant is limited. Methods: The National Cancer Database was queried to identify patients diagnosed with sarcomatoid bladder cancer from 2004 to 2018. Patients older than 18 years with cT2-4aN0-1M0 sarcomatoid bladder cancer who received curative-intent surgery were included in the analyses. Clinical T4b/N2-3/M1 disease and receipt of adjuvant chemotherapy were employed as exclusion criteria. The population was divided into two cohorts based on the receipt of NAC. Chi-Square and Mann Whitney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed to adjust for confounding factors associated with overall survival. Models were adjusted for age, race, sex, income, stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 573 patients were identified - 70% were males and 93% were White; 139 (25%) received NAC (NAC + ) while 434 (75%) did not (NAC - ). NAC + patients were younger (65 vs 71 years, p 〈 0.001). Downstaging to pT0-1N0 at the time of RC was significantly more frequent in the NAC + group compared to the NAC - group (32 (24.5%) vs. 28 (6.8%), p = 0.001). Overall survival (OS) was also significantly longer in the NAC + group (median of 40.8 vs. 19.4 months, log-rank p = 0.003). On multivariable analysis, NAC + (Hazard Ratio (HR) = 0.73, 95% CI 0.56-0.91, p = 0.02), pathological downstaging to pT0-1N0 (HR = 0.5, 95% CI 0.31- 0.8, p 〈 0.001), and any pathological upstaging (HR 4.1, 95% CI 1.5-6.6, p 〈 0.001) were independently associated with all-cause mortality, while other factors were not (Table). Conclusions: In this large retrospective analysis, administration of NAC in muscle-invasive sarcomatoid bladder cancer was associated with higher rates of downstaging to non-muscle-invasive disease at the time of RC and reduced all-cause mortality. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 343-343
    Abstract: 343 Background: The population of prostate cancer (PCa) survivors has grown over the recent decades, with many reporting long-term treatment-related physical, emotional, and financial adverse effects resulting in greater psychological distress compared to males without a history of PCa. This study analyzes the prevalence of psychological distress among PCa survivors and its impact on emergency room (ER) utilization and overall survival. Methods: We identified a cohort of 3,453 PCa survivors from the 2000-2018 National Health Interview Survey (NHIS) linked to the National Death Index Mortality Files through Dec 31, 2019. Deaths that occurred during the first two years of follow-up were excluded from analyses to minimize the likelihood of reverse causation. The Kessler Psychological Distress Scale (K6) was used to quantify psychological distress. Severe, moderate, and none/low mental distress have been validated for thresholds K6≥13, 13 〉 K6 ≥5, and 5 〉 K6 ≥0. Its association with self-reported ER utilization during the 12 months preceding the survey and all-cause mortality was estimated using weighted multivariable logistic regression and Cox proportional hazards regression, respectively. Models were adjusted for age, sex, race, educational attainment, comorbidities, region, year of survey, smoking status, health insurance, functional limitations, and time since cancer diagnosis. Results: Among the 3,453 PCa survivors (mean [SD] age 68.5 [7.2] years; 2479 (77.9%] non-Hispanic White, 655 (14.1%) non-Hispanic Black; median time since cancer diagnosis:5 years), 435 (11.3%) and 96 (2.4%) reported moderate and severe psychological distress respectively. PCa survivors with psychological distress tend to be younger, less educated, single, and with multiple comorbid conditions, and functional limitations. 812(22.8%) of PCa survivors visited the ER during 12 months preceding the survey. During a median follow-up of 81 months, 937(25.5%) of survivors died of all causes. After adjusting for covariates, PCa survivors with severe psychological distress were at a higher risk of ER utilization and all-cause mortality than those with moderate or no distress. Conclusions: Psychological distress was associated with increased risk of ER utilization and all-cause mortality among PCa survivors. Greater efforts are needed to understand, recognize, and alleviate such distress, as well as to enhance social and mental/physical health support in this rapidly growing community of vulnerable cancer survivors. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21600-e21600
    Abstract: e21600 Background: Combination BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) therapy is a widely accepted treatment option for patients (pts) with BRAF-V600E mutant melanoma. Although effective, these combinations exhibit high rates of adverse events (AEs), with 44% - 66% requiring dose modification or interruption and up to 26% discontinuing due to AEs in the adjuvant setting. Enhanced tolerance to BRAFi/MEKi is expected to improve pts quality of life and potentially enhance clinical outcomes. Clinicians at Roswell Park Comprehensive Cancer Center (RPCCC) have implemented a dose escalation regimen upon initiation of BRAFi/MEKi in efforts to enhance the tolerance of these combinations for pts with BRAF-V600E mutant melanoma in the adjuvant and advanced setting. Here we present a retrospective analysis of the toxicity profiles and outcomes associated with this “ramp-up” approach. Methods: Pts presenting to RPCCC in Buffalo, NY for management of stage III or IV melanoma harboring BRAF-V600E mutations were retrospectively observed from 1/2012 to 12/2020. Pts starting BRAFi/MEKi combinations, regardless of prior lines of therapy, were included unless concurrently receiving immune checkpoint inhibition. The “ramp-up” regimen involves a 25% dose of BRAFi and 50% dose of MEKi, which is gradually increased over 4 weekly intervals until full dose is achieved. Pts started on full-dose BRAFi/MEKi were included as a comparison arm. Observations included 1) demographics, 2) treatment regimens and disruptions, 3) rate and severity of AEs, 4) outcomes including best overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). Results: A total of 88 pts were analyzed (21 and 35 receiving “ramp-up” BRAFi/MEKi in the adjuvant and advanced (unresectable stage III or stage IV) setting, respectively, and 32 received full-dose (non-ramp-up) BRAFi/MEKi in the advanced setting). Demographics were similar except pts in the “ramp-up” cohorts were higher in average age (62.0 vs 56.0, p = 0.032) than pts starting at full-dose. Pts receiving adjuvant BRAFi/MEKi at “ramp-up” dosing exhibited a 4.8% (n = 1) rate of grade 3 or higher (Gr3+) AEs and 33.3% (n = 7) AE-related discontinuation rate (9.9 month average time to discontinuation). In the advanced setting, “ramp-up” vs full-dose treated pts exhibited Gr3+ AE rates of 25.7% (n = 9) vs 43.8% (n = 14; p = 0.197) and AE-related discontinuation rates of 34.4% (n = 12) vs 40.6% (n = 13; p = 0.592), respectively. Trends in overall AEs, ORR, PFS, and OS were similar to historical observations across all groups. Conclusions: This real-world analysis suggests that “ramp-up” incremental dosing of BRAFi/MEKi for pts with melanoma in the adjuvant and advanced setting may improve the tolerance and toxicity profiles of these agents without compromising their clinical efficacy, and may be of particular utility in pts with advanced age.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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