|
|
IACH NEWS OF THE WEEK |
February 2, 2026
Prepared by Dr Edwin Uriel Suárez |
|
|
|
|
How I individualize frontline treatment for chronic-phase CML [Review · How I Treat Series in Blood journal]. |
Key points: ● BCR::ABL1 activates the STAT5, PI3K, and RAS/RAF/MEK/extracellular signal-regulated kinase pathways, resulting in increased proliferation and survival. ● The firm establishment of a diagnosis of chronic-phase chronic myeloid leukemia (CP-CML) requires a bone marrow aspiration to formally assess blast percentage and the potential presence of additional cytogenetic abnormalities in patients potentially eligible for allogeneic stem cell transplantation (Allo-SCT). ● The first therapies shown to be disease modifying for CML were interferon alfa and Allo-SCT, although only a minority of patients were able to benefit from these modalities (Check out other article in this series: How I approach hematopoietic stem cell transplantation for CML in a TKI world). ● CML was the first malignancy to be treated with orthosteric (adenosine triphosphate [ATP]– competitive) small-molecule tyrosine kinase inhibitors (TKIs) that compete with ATP for its binding pocket, and disable downstream signaling. ● The availability of 5 effective and generally well-tolerated BCR::ABL1 TKIs: imatinib, dasatinib, nilotinib, bosutinib, and asciminib) for the treatment of newly diagnosed CP-CML offers patients and their treating physicians a welcome luxury of choice. ● Recently, the first-in-class allosteric (ATP-noncompetitive) BCR::ABL1 TKI, asciminib (pivotal frontline ASC4FIRST study), was approved. Asciminib targets a distinct regulatory pocket (myristoyl binding pocket) thereby inducing an autoinhibited/inactive BCR::ABL1 kinase conformation. ● The long-term outlook for patients with newly diagnosed CP-CML is excellent, with expected survival similar to age-matched controls. However, most patients are expected to require lifelong treatment. ● The choice of frontline TKI therapy is affected, in part, by the goals of treatment (Table 1 and Figure 2 in original paper). ● Although data are limited, lower doses of second generation TKIs and asciminib offer an opportunity to maximize quality of life in a substantial proportion of patients. ● As a result, important considerations when choosing frontline treatment include not only treatment efficacy but also response durability, tolerability, maximizing quality of life, avoidance of serious and irreversible toxicities, the ease of treatment administration, and, increasingly, the cost of treatment to the patient as well as to society. |
| Click for the full article |
|
|
Diagnosis, risk stratification and management of smouldering multiple myeloma [Review]. |
Key points: ● Multiple myeloma (MM) always develops from an asymptomatic precursor state called smouldering multiple myeloma (SMM: clonal bone marrow plasma cells 10–59%, or serum M-protein ≥3 g/dl, or urinary M-protein ≥500 mg/24 h and no symptoms attributable to the clone). ● Advanced imaging, especially positron emission tomography-computational tomography scan and magnetic resonance imaging, is crucial in the diagnosis of SMM, to rule out overt MM and enhance prognostication. ● Within the first 5 years following diagnosis, SMM has a tenfold higher risk of progression to MM compared with monoclonal gammopathy of undetermined significance (MGUS). ○ The clinical course of SMM is heterogeneous (Table 1 in original paper); high-risk SMM is associated with a 40–50% risk of progression to MM within the first 2 years of diagnosis. ○ Progression from MGUS to SMM and symptomatic MM is characterized by the presence of an APOBEC mutational signature, copy-number alternations, MYC structural variants and RAS mutations. ● For patients with high-risk SMM, both early therapeutic intervention and active surveillance are reasonable management options, with decisions individualized through a detailed risk–benefit discussion with the patient (Fig. 2 in original paper). ● Harmonizing post-protocol therapy will be essential for meaningful interpretation of overall survival outcomes; yet it remains a substantial challenge owing to regional regulatory approvals and variability in drug availability |
| Click for the full article |
|
|
American Society of Hematology (ASH) 2026 Guidelines on Diagnosis of Light Chain Amyloidosis. |
Key points: ● Serum and urine protein electrophoresis should not be the screening tests or only tests for suspected or confirmed light chain (AL) amyloidosis. A combination of electrophoresis and immunofixation (IFE) on serum and urine along with serum immunoglobulin free light chains (sFLC) testing are required. ● Urine IFE should be performed on a 24-hour urine collection or a random sample, the latter preferably from an early morning first void as this would be the most concentrated specimen for detection of a urine monoclonal protein. ○ Of note, 24-hour urine collection is needed for assessment of proteinuria/albuminuria for renal involvement from AL amyloidosis. ○ sFLC values should be interpreted with caution in patients with renal impairment and autoimmune conditions. Monoclonal protein testing may also help to increase the suspicion of other kidney diseases associated with monoclonal gammopathy beyond AL amyloidosis. ● Diagnostic echocardiographic findings that increase clinical suspicion for cardiac amyloidosis include unexplained left ventricular hypertrophy, reduced left ventricular global longitudinal strain (especially when accompanied by an apical sparing pattern), myocardium with a sparkling appearance, worsening degrees of diastolic dysfunction, elevation in left ventricular filling pressures, elevations in right heart pressures, and presence of varying degrees of pericardial effusion. ○ In this clinical scenario to enhance clinical suspicion, an abnormal cardiac biomarker is defined as any one, or combination of the NT pro-brain natriuretic peptide (BNP), BNP, troponin (hs, I, or T) above the reference range for that laboratory test. ● For patients without evidence of a plasma cell disorder (normal sFLC levels and no monoclonal proteins on serum and urine IFE) and suspicion of cardiac amyloidosis, the ASH Guideline Panel recommends the use of bone scintigraphy for the diagnosis of cardiac amyloid transthyretin protein amyloidosis (ATTR) (before or once diagnosis is confirmed, genetic counselling should be offered regardless of family history since family history is frequently missing in late onset hereditary ATTRv amyloidosis). ● The diagnosis of AL amyloidosis can be made effectively through surrogate biopsies which require both a bone marrow biopsy and fat pad sampling. However, target organ biopsies maybe favoured in certain clinical situations. ○ For individuals with suspected AL cardiac amyloidosis with abnormal cardiac biomarkers, diagnostic echocardiogram, and positivity in any of the following studies: serum IFE, urine IFE, or sFLC, the ASH Guideline Panel suggests either starting with performing both fat pad sampling and bone marrow biopsy or with endomyocardial biopsy. ○ A positive abdominal fat pad sampling or bone marrow biopsy with subtyping makes renal biopsy unnecessary. However, in the case of a negative fat pad sampling and bone marrow biopsy, a renal biopsy is necessary to look for amyloidosis or other pathology. ○ For individuals with a monoclonal gammopathy and generalized small or large fiber peripheral neuropathy or autonomic neuropathy suspected of having AL amyloidosis, the ASH Guideline Panel suggests performing both fat pad sampling and bone marrow biopsy over nerve biopsy. |
| Click for the full article |
|
|
Safety and efficacy of a pre-phase with dexamethasone followed by fractionated R-CHOP in diffuse large B-cell lymphoma patients with gastrointestinal involvement at diagnosis [Retrospective observational study]. |
Highlights: ● Standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, ● and prednisone) immunochemotherapy for diffuse large B-cell lymphoma (DLBCL) with gastrointestinal (GI) involvement is associated with an increased risk of severe GI complications, including perforation and acute hemorrhage. ● A pre-phase of dexamethasone (DEX) followed by fractionated R-CHOP in the first cycle, before transitioning to standard R-CHOP, significantly reduces the incidence of GI complications while preserving therapeutic efficacy in DLBCL patients with GI involvement. An approach offering a safer induction strategy without compromising survival outcomes. The authors retrospectively analyzed 65 DLBCL patients with GI involvement. Group 1 (n=33) received a 3-day pre-phase DEX followed by a fractionated R-CHOP regimen (cyclophosphamide, doxorubicin, and vincristine split on days 1 and 4) in cycle 1, then transitioned to standard R-CHOP from cycle 2 onwards. Group 2 (n=32) received six cycles of standard R-CHOP without pretreatment. No treatment-related GI perforation or acute hemorrhage occurred in Group 1, compared with an incidence of 18.7% in Group 2 (p=0.03). There were no significant differences in overall response rate (84.9% vs. 82.7%), 5-year progression-free survival (73.0% vs. 68.1%; p=0.62), or 5-year overall survival (83.7% vs. 78.0%; p=0.58). Hematologic toxicities were comparable between groups, and no treatment-related deaths occurred in Group 1. |
| Click for the full article |
|
|
|
|
IACH Webinars |
Stay tuned for the upcoming IACH webinars |
| Click here |
|
|
|
|
|
