Avatrombopag Improves Persistent Chemotherapy-Induced Thrombocytopenia in Gastrointestinal Cancers: Results From the Phase II ACT-GI Trial
Persistent chemotherapy-induced thrombocytopenia can disrupt cancer treatment by forcing dose reductions and delays. In the phase II ACT-GI trial, oral avatrombopag improved platelet recovery and helped more patients with gastrointestinal cancers complete chemotherapy without CIT-related treatment modifications.
KEY FINDINGS: Avatrombopag significantly improved platelet recovery and reduced the likelihood of recurrent CIT that would interfere with chemotherapy delivery in patients with GI cancers. The oral administration and once-daily dosing may offer a practical approach to managing persistent CIT. However, the trial enrolled only 47 patients and was stopped early for efficacy, which may affect the precision of the estimated treatment benefit. The findings establish efficacy for the study's platelet and chemotherapy-delivery endpoints, but do not demonstrate improved cancer survival or other long-term oncologic outcomes. Larger studies are needed to establish the durability of benefit, broader safety profile, and impact on cancer treatment outcomes. ASCO Publications
BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a clinically important complication of cytotoxic cancer treatment. Persistent thrombocytopenia can lead to repeated chemotherapy delays, dose reductions, and compromised treatment intensity, potentially affecting cancer outcomes. Management remains challenging because widely available approved therapies are limited. Avatrombopag, an oral thrombopoietin receptor agonist, stimulates platelet production and may offer an alternative to injectable therapies for patients with persistent CIT. The ACT-GI trial evaluated its efficacy and safety in patients with gastrointestinal (GI) cancers receiving cytotoxic chemotherapy.
DETAILS: ACT-GI was a multicenter, randomized, double-blind, placebo-controlled, investigator-initiated phase II trial conducted in the United States. Adults with GI cancers and persistent CIT were randomly assigned in a 1:1 ratio to receive avatrombopag or placebo. Persistent CIT was defined as a platelet count of ≤85 x 109/L on the first day of a chemotherapy cycle, despite sufficient time for recovery from the preceding cycle. The primary endpoint was successful platelet recovery to ≥100 x 109/L, completion of the on-study chemotherapy cycle without dose modification or delay due to thrombocytopenia, and prevention of CIT recurrence at the subsequent cycle. Treatment began with avatrombopag 40 mg once daily, with protocol-directed dose adjustments. The trial enrolled 47 patients, including 23 assigned to avatrombopag and 24 to placebo. Enrollment was stopped at a planned interim analysis after prespecified efficacy criteria were met. The primary endpoint was achieved by 16 of 23 patients receiving avatrombopag (70%; 95% CI, 47 to 87) compared with 4 of 24 patients receiving placebo (17%; 95% CI, 5 to 37; Z = 3.67, P .001). Platelet recovery to ≥100 x 109/L during the initial treatment period occurred in 19 of 23 patients (83%) in the avatrombopag group and 11 of 24 patients (46%) in the placebo group. At the end of the chemotherapy treatment period, median platelet counts were 157 (IQR, 136-202) x 109/L with avatrombopag and 72 (IQR, 68-134) x 109/L with placebo. Adverse events occurred in 78% of patients receiving avatrombopag and 46% receiving placebo. Serious adverse events were reported in 17% and 0%, respectively. No serious adverse events were attributed to the study drug, and no treatment-related adverse events resulted in death or discontinuation of study medication.
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Source: Al-Samkari, H., Shatzel, J. J., Panch, S.R., et al. Avatrombopag Versus Placebo for Persistent Chemotherapy-Induced Thrombocytopenia in GI Cancers: The Phase II ACT-GI Trial. Journal of Clinical Oncology. 2026; 44(31): 3006-3014. Published: November 1, 2026. DOI: 10.1200/JCO-26-00568.
Stepwise Treatment Approach May Improve Management of Conjunctival Melanoma and Precursor Lesions
A stepwise, individualized treatment strategy may help improve disease control in patients with conjunctival melanoma and precursor lesions. A 10-year retrospective study identified residual pigmentation and nonbulbar tumor involvement as important factors associated with local recurrence, while ulceration and greater tumor thickness were linked to metastatic risk.
KEY FINDINGS: An individualized, sequential treatment strategy may provide an effective approach to managing conjunctival melanocytic lesions across different histopathological grades. Topical chemotherapy may be particularly useful in diffuse lesions that cannot be completely removed surgically, while radiotherapy and additional chemotherapy may have a role in localized full-thickness HG-CMIL and invasive disease. Persistent pigmentation following initial treatment and nonbulbar tumor location warrant particular attention because of their association with local recurrence. In invasive conjunctival melanoma, ulceration, nonbulbar involvement, and greater tumor thickness may help identify patients at increased risk of metastatic spread. The findings should be interpreted in the context of the study's retrospective, single-center design, incomplete long-term follow-up in some patients, and limited metastatic events. Further multicenter research is needed to establish the comparative effectiveness of individual treatment modalities.
BACKGROUND: Conjunctival melanocytic lesions range from low-grade conjunctival melanocytic intraepithelial lesions (LG-CMIL) to high-grade lesions (HG-CMIL) and invasive conjunctival melanoma (iCoM). Their management can be challenging because of variations in disease extent, histopathological grade, and risk of local recurrence and metastasis. A sequential treatment strategy combining surgical biopsy, topical chemotherapy, and radiotherapy may help achieve disease control while tailoring treatment to individual lesion characteristics.
DETAILS: This single-center retrospective study, conducted at the Liverpool Ocular Oncology Centre, evaluated patients diagnosed with conjunctival melanocytic lesions between 2015 and 2025. The investigators assessed outcomes following an individualized, stepwise treatment approach based on histopathological findings and the clinical pattern of lesion growth. Treatment included excisional or incisional biopsy, topical chemotherapy, and adjuvant radiotherapy when indicated. The analysis included 165 eyes: 39 with LG-CMIL, 39 with HG-CMIL, and 87 with invasive conjunctival melanoma. Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate factors associated with local recurrence and metastatic disease. Particular attention was given to residual pigmentation following treatment, tumor location, ulceration, and tumor thickness. HG-CMIL lesions demonstrated the highest local recurrence rate (24.3%) and the shortest median time to recurrence (8.2 months). These lesions were frequently diffuse (71.1%), initially managed with incisional biopsy (59.0%), and associated with persistent residual pigmentation (55.6%). Local recurrence rates were 11.1% for LG-CMIL and 15.0% for invasive conjunctival melanoma. Across all lesion types, nonbulbar involvement (HR 2.76) and residual pigmentation after primary treatment (HR 2.77) were associated with increased local recurrence risk. Metastatic disease occurred exclusively in patients with invasive conjunctival melanoma, affecting 11.4% of this group. Independent risk factors associated with metastasis included ulcerative features (HR 15.08), nonbulbar involvement (HR 7.28), and increased tumor thickness (HR 2.15).
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High-Dose Oxytocin Protocol Associated With Reduced Postpartum Hemorrhage Following Vaginal Birth
Could increasing the oxytocin dose after childbirth help prevent postpartum hemorrhage? A quality-improvement study involving 2,674 births found lower overall hemorrhage rates after implementation of a high-dose protocol, with the clearest reduction observed following vaginal delivery.
KEY FINDINGS: Implementation of a higher-dose oxytocin protocol during the third stage of labor was associated with a reduction in overall PPH, primarily driven by improved outcomes following vaginal delivery. The findings suggest that modifying oxytocin administration may represent a potentially useful approach to postpartum hemorrhage prevention. However, the study's single-center, before-and-after design limits causal interpretation. The findings do not establish the optimal oxytocin dose or demonstrate that the protocol is appropriate for all delivery settings. Further research is needed to assess safety, effectiveness across delivery modes, and reproducibility in other clinical settings.
BACKGROUND: Postpartum hemorrhage (PPH) remains a major cause of maternal morbidity and mortality. Oxytocin is routinely administered after childbirth to promote uterine contraction and prevent excessive bleeding. However, the optimal prophylactic dose and administration protocol remain uncertain. A quality-improvement study conducted at a high-volume academic medical center evaluated whether increasing the oxytocin dose administered during the third stage of labor was associated with reduced postpartum blood loss and hemorrhage.
DETAILS: The single-center quality-improvement study compared maternal outcomes before and after implementation of a high-dose oxytocin protocol at the University of Michigan Health Von Voigtlander Women's Hospital. The analysis included 2,674 births between January 1 and July 6, 2024, comprising 1,309 births before and 1,365 births after protocol implementation. The standard protocol administered 30 units of oxytocin over 1 hour, followed by 3.6 units over an additional hour. The revised protocol administered 60 units over 1 hour during the third stage of labor. Implementation involved modifications to medication orders and infusion pumps, along with staff education and training. The primary outcome was PPH, defined as quantitatively measured blood loss of 1,000 mL or greater. Secondary outcomes included quantitative blood loss, with additional analyses stratified by delivery mode. Postpartum hemorrhage occurred in 14.3% of births before implementation and 11.2% afterward (adjusted relative risk [aRR], 0.77; 95% CI, 0.64-0.93). Median quantitative blood loss decreased from 444 mL (IQR, 240-749 mL) to 396 mL (IQR, 200-673 mL), with an adjusted median difference of -43 mL (95% CI, -72 to -14 mL). Among vaginal births, PPH rates decreased from 8.5% to 5.2% (aRR, 0.60; 95% CI, 0.42-0.86). Median blood loss declined from 317 mL (IQR, 153-545 mL) to 266 mL (IQR, 147-480 mL), with an adjusted median difference of -33 mL (95% CI, -65 to -1 mL). Among cesarean births, PPH occurred in 23.4% before implementation and 21.8% afterward (aRR, 0.89; 95% CI, 0.71-1.11), indicating no statistically significant reduction.
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Bundibugyo Ebola Outbreak Expands Across Countries: Kenya Reports Second Death Amid Ongoing Transmission in the Democratic Republic of the Congo
The 2026 Bundibugyo Ebola outbreak continues to expand, with sustained transmission in the Democratic Republic of the Congo and imported cases reported in Kenya and Nigeria. Kenya has reported a second death, highlighting the importance of rapid case detection, isolation, and contact tracing.
KEY FINDINGS: The outbreak is caused by Bundibugyo virus, a distinct Ebola virus species for which no licensed vaccine or specific treatment is currently available. This limits the availability of virus-specific medical countermeasures and reinforces the importance of early diagnosis, supportive clinical care, and rigorous infection prevention and control.
Healthcare facilities should maintain heightened awareness of compatible illness in patients with relevant travel or exposure histories. Prompt identification, appropriate isolation, laboratory testing, contact tracing, and coordinated public health response remain critical to reducing transmission. ECDC continues to monitor the outbreak and provide epidemiological updates and risk assessments.
BACKGROUND: An outbreak of Ebola disease caused by Bundibugyo virus (BDBV) has been ongoing in the Democratic Republic of the Congo (DRC) since May 2026. The outbreak has expanded beyond the DRC, with imported cases reported in Kenya and Nigeria during October. The emergence of cases across multiple countries underscores the importance of early case recognition, cross-border surveillance, infection prevention and control (IPC), and coordinated public health preparedness.
DETAILS: According to the European Centre for Disease Prevention and Control (ECDC), as of 29 October 2026, the DRC had reported 10,274 confirmed cases and 4,992 related deaths, based on data through 28 October. Community transmission continues across eight provinces. Kenya reported nine confirmed cases, including two deaths, as of 26 October. All cases were epidemiologically linked to the initial imported case, with no evidence of wider community transmission reported in the available assessment. The second death was reported on 23 October in a patient who was the third confirmed case in the Kenyan cluster.
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Nigeria reported an Ebola case on 20 October in an individual with a travel history to Uganda. The patient was subsequently medically evacuated to Switzerland. As of 29 October, 62 contacts had been identified and were under follow-up. Epidemiological investigations and contact tracing remain ongoing.
The outbreak continues to pose a substantial public health challenge, particularly in the DRC, where sustained community transmission and high mortality have been reported. The expansion into Kenya and Nigeria highlights the potential for international spread through population movement and travel.
In Kenya, the identification of nine cases, including two deaths, within a single epidemiologically linked cluster suggests that contact tracing and isolation have been central to containing transmission. However, the continued occurrence of cases requires sustained monitoring. ECDC emphasizes that the outbreak may be larger than currently reported because of gaps in epidemiological information and incomplete contact follow-up.
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Source: European Centre for Disease Prevention and Control (ECDC). Ebola disease: Multi-country outbreak 2026. ECDC. 2026; Published: October 30, 2026.
Single-Dose CRISPR Gene Editing Reduces Hereditary Angioedema Attacks by 87%
A single infusion of investigational CRISPR-based lonvoguran ziclumeran reduced monthly hereditary angioedema attacks by 87% compared with placebo in the phase 3 HAELO trial. Although the findings point to the potential of gene editing as a treatment strategy for this rare genetic disorder, longer follow-up is needed to establish durability and assess uncommon or delayed safety risks.
KEY FINDINGS: A single infusion of investigational CRISPR-based lonvo-z substantially reduced HAE attack frequency compared with placebo in the phase 3 HAELO trial. The findings support further development of in vivo gene editing as a potential long-term treatment strategy for HAE. However, the trial was relatively small and follow-up remains limited for assessing the durability of gene editing and uncommon or delayed adverse effects. Longer-term monitoring and additional evidence will be important to establish the treatment's sustained efficacy and safety. Lonvo-z remains investigational; these results should not be interpreted as establishing it as an approved replacement for currently available HAE therapies.
BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of swelling that can affect the skin, gastrointestinal tract, and upper airway. Laryngeal attacks can be life-threatening. Current management relies on preventive and on-demand therapies, often requiring repeated administration. In vivo gene editing offers a potential alternative by targeting the underlying pathway responsible for attacks. The phase 3 HAELO trial evaluated lonvoguran ziclumeran (lonvo-z), an investigational CRISPR-based treatment administered as a single intravenous infusion.
DETAILS: In this randomized, double-blind, placebo-controlled phase 3 trial, 80 patients aged 16 years or older with HAE associated with C1 inhibitor deficiency were assigned in a 2:1 ratio to receive a single 50-mg intravenous infusion of lonvo-z (52 patients) or placebo (28 patients). The primary endpoint was the rate of investigator-confirmed HAE attacks per month from week 5 through week 28 after infusion. Follow-up data were available through February 10, 2026, with a median follow-up duration of 7.5 months (range, 4.9-12.8 months).
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The least-squares mean monthly HAE attack rate from weeks 5 through 28 was 0.26 (95% confidence interval [CI], 0.15-0.45) in the lonvo-z group, compared with 2.10 (95% CI, 1.55-2.86) in the placebo group. This represented an 87% relative reduction in monthly attacks (95% CI, 78%-93%; P < .001).
Adverse events occurring during or after infusion through week 28 were reported in 92% of patients receiving lonvo-z and 86% receiving placebo. Events reported more frequently with lonvo-z included infusion-related reactions, headache, fatigue, back pain, and upper respiratory tract infection. No serious adverse events or adverse events of grade 3 or higher were reported in the lonvo-z group during the reported period.
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Source: Cohn, D. M., Gurugama, P., Longhurst, H. J., et al. Lonvoguran Ziclumeran — In Vivo CRISPR Gene Editing in Hereditary Angioedema. New England Journal of Medicines. 2026; 395: 1471-1482. Published: October, 2026. DOI: 10.1056/NEJMoa2600931.
Lean MASLD Associated With Higher In-Hospital Mortality and Hepatic Complications
Lean body weight does not necessarily mean lower risk in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In a US hospitalization-based analysis, lean MASLD was associated with higher odds of mortality, hepatic complications, and several gastrointestinal malignancies compared with nonlean MASLD. Although the observational findings cannot establish causality, they highlight the importance of assessing disease severity rather than relying on BMI alone.
KEY FINDINGS: Lean MASLD may carry substantial hepatic and oncological risks despite the absence of obesity. Clinicians should avoid relying on BMI alone when assessing disease severity and should consider liver complications and associated comorbidities in patients with steatotic liver disease across body-weight categories.
The study's retrospective design and reliance on hospitalization data are important limitations. The findings do not establish causality and may not be generalizable to all individuals with MASLD, particularly those managed in outpatient settings. Further research is needed to clarify the mechanisms underlying these associations and determine how risk assessment and management should be tailored to lean patients.
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important cause of chronic liver disease and related complications. Although it is commonly associated with overweight and obesity, the condition also occurs in individuals with a lean body mass index (BMI). The clinical risks in this population remain an important area of investigation, particularly because normal body weight may not reliably indicate the absence of advanced liver disease or metabolic dysfunction.
DETAILS: Researchers conducted a retrospective comparative study using the US National Inpatient Sample (NIS) database from 2016 through 2020. Adult hospitalizations involving MASLD were identified, with exclusions for other specified liver conditions, including viral hepatitis, alcoholic hepatitis, primary biliary cholangitis, hereditary hemochromatosis, autoimmune hepatitis, and Wilson disease. Outcomes were compared between patients classified as lean and those with nonlean BMI. The analysis assessed mortality, hepatic complications, and gastrointestinal malignancies among hospitalized patients with MASLD.
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Hospitalized patients with lean MASLD had significantly higher odds of mortality than those with nonlean MASLD (odds ratio, 2.10; P .001). The lean group also had higher odds of cirrhosis, portal hypertension, spontaneous bacterial peritonitis (SBP), and ascites.
In addition, lean MASLD was associated with higher odds of several gastrointestinal malignancies, including esophageal, gastric, pancreatic, and colorectal cancers. These findings suggest that lean body weight should not be interpreted as a reliable indicator of lower clinical risk in patients hospitalized with MASLD.
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Source: Desai, C., Lohani, S., Sharma, A. R., et al. Lean Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Hepatic and Oncological Outcomes. Journal of Clinical Gastroenterology. 2026; 60(10): 922-926. Published: November/December 2026. DOI: 10.1097/MCG.0000000000002153.s
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