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IACH NEWS OF THE WEEK

September 14, 2025
Prepared by Dr Edwin Uriel Suárez

Apixaban for Extended Treatment of Provoked Venous Thromboembolism [Phase 3 clinical trial]

Highlights:

-        The appropriate duration of anticoagulation for venous thromboembolism (VTE) in patients who have a transient provoking factor (e.g., surgery, trauma, or immobility) and concomitant enduring risk factors is uncertain.

-        In this double-blind, randomized trial, adult patients with provoked VTE and enduring risk factors, treated with low-intensity therapy with apixaban for 12 months, had a lower risk of symptomatic recurrent VTE than those on placebo, with a low risk of major bleeding.

 

In this single-center study (HI-PRO; NCT04168203; Brigham and Women’s Hospital in Boston, USA), adults with VTE after the occurrence of a transient provoking factor who had at least one enduring risk factor and had completed at least 3 months of anticoagulation were assigned to receive oral apixaban (at a dose of 2.5 mg twice daily; n=300) or placebo (n=300) for 12 months. The mean age was 59.5 years. The trial population had a broad range of provoking factors and enduring risk factors (mainly obesity and chronic inflammatory or autoimmune disorder; see Table 2 in the original publication). Symptomatic recurrent VTE occurred in 4 of the 300 patients (1.3%) in the apixaban group and in 30 of the 300 patients (10.0%) in the placebo group (hazard ratio [HR] 0.13; 95% confidence interval [CI], 0.04 to 0.36; P<0.001). Major bleeding occurred in 1 patient in the apixaban group and none in the placebo group. Clinically relevant nonmajor bleeding was observed in 14 of 294 patients (4.8%) in the apixaban group and in 5 of 294 patients (1.7%) in the placebo group (HR 2.68; 95% CI, 0.96 to 7.43; P=0.06).  
Click for the full article

Arsenic Trioxide and All-Trans Retinoic Acid Combination Therapy for the Treatment of High-Risk Acute Promyelocytic Leukemia: Results From the APOLLO Trial

We mentioned the results in “IACH NEWS OF THE WEEK: Highlights 29th European Hematology Association Hybrid Congress (EHA2024; June 13-16, Madrid, Spain).” Here is the summary of the full publication.

 

Highlights:

-        The study was discontinued prematurely in August 2022, due to slow recruitment during the COVID-19 pandemic, and expiration of study-drug reserved for the trial.

-        Two-year event-free survival (EFS) was significantly higher among patients treated with all-trans retinoic acid plus arsenic trioxide (ATRA-ATO) when compared with patients treated with ATRA plus anthracycline-based chemotherapy (ATRA-CHT), and rates of molecular relapse were significantly lower among patients receiving ATRA-ATO when compared with patients receiving ATRA-CHT.   

-        The results of the APOLLO trial support the use of ATO and ATRA for the treatment of newly diagnosed patients with high-risk acute promyelocytic leukemia (APL).

 

In this phase III clinical trial  (EudraCT 2015-01151-68; NCT02688140) adult patients with newly diagnosed high-risk APL in the ATRA-ATO arm (n =68) received ATO 0.15 mg/kg once daily and ATRA 45 mg/m2 twice daily until complete remission (CR), with two doses of idarubicin 12 mg/m2 on days 1 and 3, followed by consolidation therapy (four ATRA-ATO cycles). Patients in the ATRA-CHT arm (n= 65) received induction with ATRA 45 mg/m2 twice daily and idarubicin 12 mg/m2 once daily on days 1, 3, 5, and 7, followed by three cycles of chemotherapy-based consolidation and 2 years of maintenance therapy. After a median follow-up of 37 months (range, 1.7-88.6 months), 2-year EFS was 88% in the ATRA-ATO arm and 71% in the ATRA-CHT arm (hazard ratio, 0.4 [95% confidence interval, 0.17 to 0.92]; log-rank test P = 0.02). At a median of 7.8 and 12.1 months from achievement of CR, molecular relapse occurred in one (1.5%) ATRA-ATO patient versus eight (12.3%) ATRA-CHT patients (P=0.014). Overall, 32% and 68% of patients receiving ATRA-ATO and ATRA-CHT, respectively, reported serious treatment-emergent adverse events (P < 0.01).
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Monoclonal Antibodies in the Pathogenesis of Heparin-Induced Thrombocytopenia [Case series]

Highlights:

-        Heparin-induced thrombocytopenia (HIT) is an immune-mediated platelet disorder caused by antibodies that target complexes of platelet factor 4 (PF4) and heparin. HIT has been characterized as a polyclonal immune response; however, studies of other rare anti-PF4 disorders have identified clonally restricted antibodies.

-        This case series study finding provides insight into the pathogenesis of HIT and has implications for improved diagnostics and targeted therapeutics.

 

Serum samples from all nine patients with HIT were positive for platelet-activating antibodies against PF4–heparin by enzyme immunoassay, as well as the P-selectin expression assay, and six samples (67%) had a monoclonal antibody detectable by immunofixation electrophoresis. The affinity-purified antibodies against PF4–heparin from all nine samples activated platelets in the P-selectin expression assay, and mass spectrometry showed monoclonality. After affinity purification, antibody-depleted serum samples lost binding activity in the enzyme immunoassay and functional activity in the P-selectin expression assay, which confirmed the removal of the pathogenic antibodies. The epitopes on PF4 targeted by anti–PF4– heparin antibodies from serum samples were the same as those targeted by the affinity-purified monoclonal antibodies. 
Click for the full article

Community-acquired respiratory virus infections in patients with haematological malignancies or undergoing haematopoietic cell transplantation: updated recommendations from the 10th European Conference on Infections in Leukaemia [Consensus]

Key points:

●      Laboratory-confirmed influenza virus respiratory tract infectious disease (RTID) in allogeneic and autologous haematopoietic cell transplantation (HCT) recipients, or patients with haematological malignancies who test positive during chemotherapy and in the following 6 months, should be treated with antivirals as soon as possible, preferably less than 48 hours (h) after symptom onset.


●      If rapid nucleic acid testing or direct antigen testing is not available, patients undergoing HCT and with haematological malignancies with compatible symptoms or signs and an epidemiological risk (e.g., during influenza season) should be treated promptly while awaiting laboratory confirmation.


●      The first-line antiviral is oseltamivir.


●      The recommended adult dose of oseltamivir is 75 mg twice per day until clinically significant improvement, usually within 5–10 days.


●      The first-line alternative antiviral is baloxavir marboxil.


●      Zanamivir inhalation is available for outpatient treatment of uncomplicated influenza, but data are insufficient for first-line treatment of patients with haematological malignancies or those undergoing HCT.


●      Due to insufficient data, ribavirin should not be used as pre-exposure or post exposure prophylaxis in adults or in children.


●      Allogeneic HCT recipients:

○      Recipients with high risk for progression to, or diagnosed with, respiratory syncytial virus-lower respiratory tract infectious disease (RSV-LRTID) should be considered for treatment with ribavirin.

○      For guidance on defining high risk for poor outcome, the MD Anderson Immunodeficiency Score Index or the Basel Severe Immunodeficiency grading can be considered.

○      In recipients at low risk for progression to RSV-LRTID, ribavirin treatment can be withheld.

○      Systemic ribavirin can be administered orally at 10–30 mg/kg of bodyweight in three divided doses (max 600 mg/8 h, up to a maximum dose of 1800 mg/day).

○      Patients receiving systemic ribavirin should be monitored and managed for adverse events (e.g., haemolysis, abnormal liver function tests, drug–drug interactions, or declining renal function).

○      Although currently rarely used because of high costs and demanding logistics, 2 g aerosolised ribavirin can be administered for 2 h every 8 h for 7–10 days to treat RSV.

○      Aerosolised ribavirin therapy should be accompanied by measures avoiding environmental exposure, and thereby potentially teratogenic effects, in pregnant health-care providers and visitors.

○      Patients on aerosolised ribavirin should be monitored and treated for adverse events including claustrophobia, bronchospasm, nausea, conjunctivitis, and declining pulmonary function.

○      For patients at high risk for progression to, or who have been diagnosed with, RSV-LRTID, adjunct treatment could be considered with at least three doses of intravenous immunoglobulin at 0.5 g/kg bodyweight within 1–2 weeks of diagnosis.

○      For patients testing positive for RSV and hypogammaglobulinaemia (<4.5 g/L), treatment with at least three doses of intravenous immunoglobulin at 0.5 g/kg bodyweight administered within 1–2 weeks of diagnosis could be considered.

○      Use of corticosteroids at more than 1 mg/kg per day at diagnosis of RSV-LRTID has been associated with disease progression and mortality; thus, reducing corticosteroid administration to less than 1 mg/kg of bodyweight can be considered if feasible.


●      Management considerations for RSV in patients undergoing autologous HCT or in patients with haematological malignancies:

○      Treatment of patients with a diagnosis of RSV-LRTID with ribavirin should be considered.

○      Systemic or aerosolised ribavirin administration and monitoring should follow the recommendations outlined for allogeneic HCT recipients.

○      For patients with RSV-LRTID (or at high risk for progression to RSV-LRTID) and hypogammaglobulinaemia (<4.5 g/L), adjunct treatment with at least three doses of intravenous immunoglobulin at 0.5 g/kg of bodyweight administered within 1–2 weeks of diagnosis can be considered. 
Click for the full article

BLAST: a globally applicable and molecularly versatile survival model for chronic myelomonocytic leukemia [Retrospective cohort]

Highlights:

-        The authors propose a new clinical survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables. They examined additional impact from mutations and karyotype. 

-        Molecular information helps identify BLAST low- or intermediate-risk patients in whom allogeneic transplant is advised earlier than later.

 

A total of 457 molecularly annotated patients were considered. Multivariable analysis identified circulating blasts ≥2% (1 point), leukocytes ≥13 × 109/L (1 point), and severe (2 points) or moderate (1 point) anemia as preferred risk variables in developing a clinical risk stratification tool for overall survival (OS), acronymized to “BLAST”: low-risk (0 points; median, 63 months); intermediate-risk (1 point; median, 28 months; hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.6-3.0), and high-risk (2-4 points; median, 13 months; HR, 5.4; 95% CI, 4.1-7.3); the corresponding 3/5-year OS rates were 68%/53%, 43%/18%, and 12%/1%. BLAST model performance (area under the receiver operating characteristic curve [AUC] 0.77/0.85 at 3/5 years) was shown to be comparable to that of the molecular CMML-specific prognostic scoring system (AUC 0.73/0.75) and the international prognostic scoring system-molecular (AUC 0.73/0.74). Multivariable analysis of mutations and karyotype identified PHF6MUT and TET2MUT as being “favorable” and DNMT3AMUT, U2AF1MUT, BCORMUT, SETBP1MUT, ASXL1MUT, NRASMUT, PTPN11MUT, RUNX1MUT, TP53MUT, and adverse karyotype, “unfavorable.” Molecular information was subsequently encoded in a combined clinical-molecular risk model (BLAST-mol; AUC 0.80/0.86 at 3/5 years) that included the aforementioned BLAST clinical risk variables and a 3-tiered molecular risk score. BLAST and BLAST-mol were subsequently validated by 2 separate external cohorts. Independent risk factors for blast transformation included DNMT3AMUT, ASXL1MUT, PHF6WT, leukocytes ≥13 × 109/L, and ≥2% circulating or ≥10% bone marrow blasts.

 

Accompanying the original article, the editorial commentary mentions: “Nevertheless, using molecular risk variables alone failed to significantly differentiate the 3 risk groups in the validation cohorts (low vs. intermediate in the MD Anderson cohort and intermediate vs. high in the Milan cohort), and validation of the favorable prognostic significance of PHF6 and TET2 mutations in other large cohorts is needed given the enrichment of otherwise low-frequency PHF6-mutated patients in the Mayo cohort”. It also designs appropriate questions for further research into this type of myeloid neoplasms. 
Click for the original paper
Click for the commentary

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