tbuckley/cabot-search huggingface dataset:
Innovative Treatments for Rare Anemias
Authors: Maria Domenica Cappellini, Alessia Marcon, Bruno Fattizzo, Irene Motta
Journal: HemaSphere (2021)

Rare anemias (RA) are mostly hereditary disorders with low prevalence and a broad spectrum of clinical severity, affecting different stages of erythropoiesis or red blood cell components. RA often remains underdiagnosed or misdiagnosed, and treatment options have been limited to supportive care for many years. During the last decades, the elucidation of the molecular mechanisms underlying several RA paved the way for developing new treatments. Innovative treatments other than supportive care and allogeneic bone marrow transplantation are currently in clinical trials for β-thalassemias, sickle cell disease (SCD), and congenital hemolytic anemias. Recently, luspatercept, an activin receptor ligand trap targeting ineffective erythropoiesis, has been approved as the first pharmacological treatment for transfusion-dependent β-thalassemia. L-glutamine, voxelotor, and crizanlizumab are new drugs approved SCD, targeting different steps of the complex pathophysiological mechanism. Gene therapy represents an innovative and encouraging strategy currently under evaluation in several RA and recently approved for β-thalassemia. Moreover, the advent of gene-editing technologies represents an additional option, mainly focused on correcting the defective gene or editing the expression of genes that regulate fetal hemoglobin synthesis. In this review, we aim to update the status of innovative treatments and the ongoing trials and discuss RA treatments’ future directions. Interestingly, several molecules that showed promising results for treating one of these disorders are now under evaluation in the others. In the near future, the management of RA will probably consist of polypharmacotherapy tailored to patients’ characteristics.
Finding the missing millions: Integrating automated viral hepatitis screening in a hospital with care and treatment in a primary care setting.
Authors: Ruth Brogden, Su Wang, Binghong Xu
Journal: Journal of Clinical Oncology (2021)

108 Background: Rates of hepatocellular carcinoma (HCC) are rising in the US. Patients at Saint Barnabas Medical Cancer Center (SBMC) present with late-stage HCC at higher rates (29%) compared to the national (16%). Chronic Hepatitis C (HCV) and Hepatitis B (HBV) are major drivers of liver cancer, yet screening rates are low. Finding these missing millions is important to reducing rates of HCC. An automated emergency department (ED) viral hepatitis (VH) screening program was initiated in 2018 at SBMC. In January 2020, it was expanded to the inpatient setting and HCV screening was modified from cohort screening (those born in 1945-65) to a one time test for anybody 18 years or over, per updated Centers for Disease Control (CDC) and USPSTF (US Preventive Services Taskforce) recommendations. Methods: The electronic medical record (EMR) was modified to automate screening. HBV testing is triggered by a patient’s country of birth or race, and HCV testing is triggered by age over 18 and no previous testing. The automated HCV (HCV Ab with reflex to HCV RNA) or HBV (HBsAg) lab orders lead to an EMR notification to the nurses of patient eligibility and education is provided to patients. Alerts of positive results are sent to nursing staff, physicians, and the patient navigator (PN). The PN is sent a real-time secure text message and works individually with patients to arrange linkage-to-care (LTC) for evaluation and treatment. Results: From March 2018 - December 2020, 44,002 patients were screened for HCV and 884 (2.0%) were HCVAb+ and 242 (0.55%) HCV RNA+. For HBV, 21,328 patients were screened and 212 (0.99%) were HBsAg+. The expanded screenings accounted for 8,716 (19.8%) of the total HCV screenings. Individuals born outside the 1945-65 birth cohort (younger and older) made up 76.2% of those screened and 41% of the infected. The top 3 countries for HBV screenings were Haiti, Jamaica, and Ecuador. LTC rates, defined as attending first medical appointment or already in care, were 86.8% for HCV and 85.4% for HBV. Of those linked to care, 43 HCV+ patients were seen at a outpatient primary care practice part of SBMC, and of those, 39 initiated HCV cure therapy and 33 were cured (confirmed sustained virologic response at 12 weeks), and 35 HBV+ patients were seen and 6 initiated treatment. Conclusions: This automated program for VH has led to a significant scale up of screening with successful LTC and treatment of patients. Expansion to universal screening of all adults and to the inpatient setting found additional viral hepatitis patients who would have otherwise been missed. In addition to the automated screening, a multidisciplinary team including internists, pharmacists, and patient navigators were part of creating a primary care based program. Integration of viral hepatitis screening and care in a hospital system can be initial steps towards establishing liver cancer prevention program.
Sixty seconds on . . . Ronaldo and Coke
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Quite the opposite. Cristiano Ronaldo—the footballing superstar and global icon—has been widely praised by public health experts after he shunned Coca-Cola during a press conference at the UEFA Euro 2020 football championships, where the soft drinks giant is an official sponsor.

Not as far as we’re aware (although he has advertised both brands in the …
The imprecise promise of the Precision Medicine Initiative (PMI): Where we got it wrong and how can we fix it?
Authors: Natasha Clinton, Kashyap B. Patel
Journal: Journal of Clinical Oncology (2021)

e15102 Background: Over the last several years, science has taken strides in how we understand and treat cancer. We have learned that each person’s cancer is unique, in part because it is influenced by a patient’s biological characteristics, environmental exposures, lifestyle and epigenetic influence. There is excitement about the potential of PMI to transform healthcare delivery and improve population health. Targeted therapies developed based on specific mutations can result in improved outcomes and reduced toxicities. Limited knowledge of cancer biology and the genomic underpinnings of cancer in racial and ethnic minorities diminishes the potential of PMI. Previous efforts of obtaining biospecimens from institutional or local biobanks presents a challenge of inadequate representation of racial and ethnic diversity. This can result in exacerbation in the therapies efficaciousness. Methods: Numerous research studies have surfaced indicating that PMI has resulted in widening racial and ethnic health care disparities since state-of-the art diagnostic and treatment options are unequally distributed across the entire cancer population. A literature review highlighted the racial inequalities and disparities. Results: A report examining the racial diversity of samples in TCGA found that whites were overrepresented in the U.S. population while Asian and Hispanic patients were underrepresented at a 5 percent frequency. In the BATTLE study, 82 percent of participants were white, and only 6% were African American (AA). The NCI-MATCH trial preliminary numbers show that AAs accounted for about 10 percent of patients. Therefore, it should not be assumed that the response rates or clinical effectiveness of the therapeutics tested in these trials will generalize to all racial and ethnic groups. The underrepresentation of racial and ethnic minorities in cancer clinical trials and prevention research, along with the documented challenges to enrolling these individuals into studies pose a barrier for the implementation of precision medicine in these populations. Collectively, these challenges can slow the pace of medical innovation, decrease the generalizability of research findings, lead to incorrect interpretations, and limit our full understanding of precision medicine. Conclusions: It is imperative we develop solutions to solve for issues identified related to precision medicine testing and treatment development. We have developed a framework to address disparities in PMI through community-based initiatives. A two-step solution could be considered to address this unmet need. Through the development of a registry and biospecimen banking as well as just in time trials that include pharmacogenomics, we can follow the patient journey to identify unique characteristics by race and/or socioeconomic status to begin solving for the disparities across the population.
Association between baseline geriatric domains and survival in older adults with chronic lymphocytic leukemia (CLL).
Authors: Julia Rice, Ryan David Nipp, Daniel E Lage, Ashley M. Nelson, Richard Newcomb, Mitchell W. Lavoie, Carlisle E. W. Topping, Christine Ritchie, Areej El-Jawahri, Patrick Connor Johnson
Journal: Journal of Clinical Oncology (2021)

12041 Background: CLL is a disease that commonly affects older adults. Although the value of geriatric assessment is increasingly being recognized in older adults with cancer, few studies have examined the relationship between baseline geriatric domains and clinical outcomes in older adults with CLL. Methods: We conducted a secondary data analysis of 369 adults diagnosed with CLL and treated in a phase 3 randomized trial of patients age ≥65 with bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone. We evaluated geriatric domains of functional status (activities of daily living [ADL], instrumental activities of daily living [IADL], Timed “Up and Go,” and number of falls in last 6 months), psychological status (Mental Health Inventory), social activity (Medical Outcomes Study [MOS] Social Activity Survey), cognition (Blessed Orientation Memory Concentration Test), social support (MOS Social Support Tangible and Emotional/Informational subscales), and nutritional status ( &gt; 5% weight loss in the preceding 6 months). We examined associations among baseline geriatric domains with overall survival (OS) and progression-free survival (PFS) using multivariable Cox regression models. Results: The median age of patients was 71 years (range: 65-89). Most were male (67.1%) and had an ECOG performance status of 0 or 1 (96.9%). In multivariable models, the following geriatric domains were significantly associated with OS: better functional status (ADL score: HR 0.67, p = 0.012; IADL score: HR 0.98, p = 0.007); social activity score (HR 0.97, p = 0.004); and nutritional status (HR 2.58, p = 0.008). Similarly, functional status (ADL score: HR 0.77, p = 0.028; IADL score: HR 0.99, p = 0.007); social activity score (HR 0.97, p &lt; 0.001); and nutritional status (HR 2.87, p &lt; 0.001) were all associated with PFS. Additionally, the number of impaired geriatric domains was also associated with OS (HR 1.50, p = 0.004) and PFS (HR 1.45, p &lt; 0.001). Timed “Up and Go”, number of falls in last 6 months, psychological status, cognition, and social support were not significantly associated with clinical outcomes. Conclusions: Geriatric domains of functional status, social activity, and nutritional status were associated with OS and PFS in this cohort of older adults with CLL. These findings highlight the importance of assessing geriatric domains to identify high-risk patients with CLL who may benefit from additional support during their treatment.
Updated single institution outcome data from the first-in-human CEND-1 trial in metastatic pancreatic cancer.
Authors: Andrew Peter Dean, Fiona Mulligan, Geena Kelly, Emma Shaughnessy, Kate Wilson
Journal: Journal of Clinical Oncology (2021)

e16274 Background: In our phase I trial of the first-in-class agent CEND-1 with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer, we reported a preliminary overall RR of 59% in 29 patients across 3 institutions. Our site enrolled 19 of these patients and we present updated outcome data from this institution. CEND-1 is a bifunctional cyclic peptide (a.k.a. iRGD) that homes to tumors via RGD motif interaction with alphav-integrins and then transforms the solid tumor microenvironment into a temporary drug conduit via interaction with neuropilin-1. This leads to an enhanced tumor delivery of co-administered anti-cancer agents. Methods: We reviewed our updated outcome data from the first in human CEND-1 trial in pancreatic cancer. Patients received a combination of CEND-1 with nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, 15 of a 21-day treatment cycle. Data was analysed to determine response rate, progression free survival and ongoing benefit. Results: Of the 19 patients that were enrolled at this institution; 13 (69%) showed partial response, 5 (26) % had stable disease, and 1 (3.4%) had progressive disease. Median progression free survival for this cohort was 8.8 months. 4 patients (21%) remain on the trial without disease progression to date. Median treatment duration for these patients is 20 months (range 17.1 – 24.6 months). Adverse events were as previously described¹ with no new significant events or toxicities. Conclusions: Ongoing follow-up data from the CEND-1 study at our institution shows ongoing continuing benefit for patients who remain on trial with notable progression free survival. No new safety signals or adverse events have been detected with this prolonged follow-up. The randomised phase 2 trial of this combination will be proceeding later this year. Clinical trial information: ACTRN12618000804280.
Under the Radar: Global Minimum Estimates for COVID-19-associated Orphanhood and Deaths among Caregivers
Authors: S Hillis, Hjt Unwin, Y Chen, L Cluver, L Sherr, PY Goldman, O Ratmann, C Donnelly, S Bhatt, A Villaveces, A Butchart, G Bachman, L Rawlings, P Green, CA Nelson, S Flaxman
Journal: The Lancet (2021)
A phase 1 first-in-human study of the anti-LAG-3 antibody MK4280 (favezelimab) plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer.
Authors: Elena Garralda, Ammar Sukari, Nehal J. Lakhani, Amita Patnaik, Yanyan Lou, Seock-Ah Im, Talia Golan, Ravit Geva, Martin Wermke, Maria De Miguel, John Palcza, Sujata Jha, Marya F. Chaney, Jane Anne Healy, Gerald Steven Falchook
Journal: Journal of Clinical Oncology (2021)

3584 Background: Patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that progressed on ≥2 prior therapies have limited treatment options, with median OS ranging from 6-9 months (mo). In the dose-escalation phase of this first-in-human multicohort study (NCT02720068), the anti-lymphocyte activation gene (LAG)-3 antibody favezelimab (fave) was well tolerated alone and with pembrolizumab (pembro) across all dose levels (Lakhani, SITC, 2018, abstract O26). Here, we evaluate the safety and efficacy of fave alone or in combination with pembro in pts with advanced MSS CRC from the dose confirmation phase. Methods: Eligible pts with MSS PD-1/PD-L1-treatment-naïve mCRC that progressed on prior standard-of-care (3L+) were enrolled (cohort A) to receive the RP2D of 800 mg fave alone (Arm 1), 800 mg fave + 200 mg pembro (Arm 2C), or 800 mg fave + 200 mg pembro (MK-4280A) co-formulation (Arm 5), all Q3W. Treatment continued for 35 cycles or until progression, unacceptable toxicity, or investigator/pt decision. Pts with confirmed progression per irRECIST v1.1 on fave alone could crossover to 800 mg fave + pembro. Safety was assessed in all treated pts; efficacy in the full analysis set (FAS) of all treated pts with baseline scan. Objectives included safety (primary), ORR (RECIST v1.1 by investigator [secondary]), and DOR, PFS, and OS (exploratory). Interim analysis data cut-off was: Oct. 23, 2020. Results: A total of 20 pts received fave (Arm 1); 89 pts (including 9 crossover) received fave + pembro (Arms 2C+5); 12 pts (Arm 1) and 36 pts (Arms 2C+5), had PD-L1 CPS ≥1 tumors. At data cut-off, median follow-up was 5.8 months (mo) in Arm 1 and 6.2 mo in Arms 2C+5. Treatment-related adverse events (TRAEs) were 65% with fave (Arm 1) and 65.2% with fave + pembro (Arms 2C+5). Grade ≥3 TRAEs were 15% (Arm 1), and 20% [Arms 2C+5]). No grade 5 TRAEs were reported. Common TRAEs (≥15%) included fatigue (20.0%), nausea (15%) with fave, and fatigue (16.9%) with fave + pembro. Confirmed ORR was 6.3% (4PR, 1CR) with fave + pembro (Arms 2C+5). No pt receiving fave alone responded. In Arms 2C+5, median DOR was 10.6 mo (range, 5.6-12.7). ORR, OS and PFS by PD-L1 status are reported in the Table. Conclusions: Favezelimab alone or in combination with pembrolizumab had a manageable safety profile, with no treatment-related deaths. Promising antitumor activity was observed with combination therapy, including with MK-4280A, compared with monotherapy most notably in pts with PD-L1 CPS ≥1 tumors. Clinical trial information: NCT02720068. [Table: see text]
Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).
Authors: Bradley Alexander McGregor, Daniel M. Geynisman, Mauricio Burotto, Camillo Porta, Cristina Suarez Rodriguez, Maria Teresa Bourlon, Pedro C. Barata, Shuchi Gulati, Brian Stwalley, Viviana Del Tejo, Ella X. Du, Aozhou Wu, Andi Chin, Keith A. Betts, Stephen Huo, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2021)

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trial of P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]
Feasibility of digital life coaching during stem cell transplantation for multiple myeloma.
Authors: Rahul Banerjee, Chiung-Yu Huang, Lisa Dunn, Jennifer Knoche, Kelly Jean Brassil, Lindsey Jackson, Dhiren Patel, Mimi Lo, Shagun Arora, Sandy Wai Kuan Wong, Jeffrey Lee Wolf, Thomas G. Martin, Anand A. Dhruva, Nina Shah
Journal: Journal of Clinical Oncology (2021)

e24103 Background: Patients with multiple myeloma (MM) experience acute quality of life (QOL) exacerbations following autologous stem cell transplantation (ASCT) that can lead to long-term complications. Life coaching can improve QOL in a structured &amp; personalized manner. We investigated the feasibility of a digital life coaching (DLC) platform, where coaching is accomplished through phone calls and text messages, for patients with MM during ASCT. Methods: Our pilot study (clinicaltrials.gov ID: NCT04432818) enrolled adult patients with MM, English proficiency, and cellphone ownership (smartphone not required). The 16-week DLC program, beginning at Day -5 before ASCT, included unlimited digital access to a certified life coach to help with identifying and accomplishing wellness-related goals. Our primary outcome was ongoing DLC engagement (≥ 1 bidirectional conversation every 4 weeks). Secondary outcomes were ePRO assessments of QOL (PROMIS Global Health), insomnia (PROMIS Sleep Disturbances), and distress (NCCN DT). Electronic patient-reported outcome (ePRO) assessments were delivered via automated REDCap emails every 1-2 weeks. Results: Of 18 screened patients, 15 (83%) enrolled in our study; 2 patients dropped out before initiating DLC (including 1 who was unable to connect with her coach between Day -5 and 0). Of 13 remaining patients, median age was 65 (range 50-81) and 23% had an ECOG performance status of 1 (remainder 0). DLC conversations occurred a mean of every 7.6 days (range 3-28) overall and every 6.5 days (range 2.8-14) during the initial 28-day period including high-dose melphalan and hospitalization. 80% of patients maintained ≥ 1 conversation every 4 weeks. Selected ePRO results (mean ± standard error) are shown in the table. Conclusions: Certain MM patients are able to engage digitally with a life coach and complete email-based ePRO assessments during and after ASCT. Limitations of our study include selection bias and the Day -5 start date, which may be too late logistically and symptom-wise (given our ePRO findings suggestive of peak distress pre-ASCT). DLC may play an innovative and scalable role given the emphasis on remotely delivered care during the COVID-19 pandemic. A Phase II randomized study of DLC versus usual care is under way (clinicaltrials.gov ID: NCT04589286). Clinical trial information: NCT04432818. [Table: see text]
The Role of FDG PET for Evaluation of Bone Marrow Status and Prognosis in T Cell Lymphomas
Authors: Go-Un Woo, Jung Min Lee, Youngil Koh, Jin Chul Paeng, Youk Jeonghwan, Sung-Soo Yoon, Inho Kim, Dong-Yeop Shin, Junshik Hong, Hyo Jung Kim, Hyun Jung Lee
Journal: Blood (2017)