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IACH NEWS OF THE WEEK |
September 28, 2025
Prepared by Dr Edwin Uriel Suárez |
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Large B‐cell lymphoma (LBCL): EHA Clinical Practice Guidelines for diagnosis, treatment, and follow‐up |
Key points: ● Positron emission tomography computed tomography (PET‐CT) surpasses bone marrow (BM) biopsy in detecting BM involvement with large B‐cell lymphoma (LBCL) and is highly specific. The presence of nonfluorodeoxyglucose‐avid BM disease does not confer a worse prognosis. BM biopsy may be considered for selected patients in whom a coexisting hematological condition is suspected (e.g., low‐grade lymphoma or myelodysplasia), and where this would inform clinical management, but is otherwise unnecessary. ● First‐line management for LBCL (See FIGURE 1 - Algorithm 1L LBCL treatment- in the original paper) can be informed by interim PET to assess chemosensitivity, with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) or polatuzumab vedotin rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola‐R‐CHP) for advanced stages depending on International Prognostic Index (IPI) scores. ● Primary mediastinal B‐cell lymphoma (PMBCL) management favors R‐CHOP given every 14 days (R‐CHOP14) or dose‐adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone and rituximab (DA‐EPOCH‐R) without radiotherapy in complete responders. ● Elderly patients, unfit or not (≥80 years or <80 with poor fitness), need geriatric assessment to guide therapy, often R‐miniCHOP or non‐anthracycline regimens. ● The value of central nervous system (CNS) prophylaxis remains uncertain. CNS‐IPI scores and specific anatomical sites help identify high‐risk patients; magnetic resonance imaging and cerebrospinal fluid analysis are recommended in high risk of CNS relapse (CNS-IPI ≥4–6; two or more than two initial extra‐nodal sites; involvement of specific extranodal sites, named immune privileged sites: testis, breast, epidural space, orbit, kidney, and adrenal gland). ● Approximately 30%–40% of patients with LBCL experience relapsed or refractory disease after first line (1L) treatment. Treatment strategies vary based on the timing of relapse (<1 year or ≥1 year). See FIGURE 2 in the original paper. ○ For those refractory or relapsing within <1 year and fit for therapy, chimeric antigen receptor T (CART) therapies are the gold standard in 2L. ○ CART in CART‐naïve patients and bispecific antibodies appear to be the best approach in 3L. |
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ONS/ASCO Guideline on the Management of Antineoplastic Extravasation |
Key points: See FIGURE 1 in the original paper: “Algorithm on the management of antineoplastic extravasation of vesicant or irritant with vesicant properties in adults”. ● Table 1 in the original paper lists the vesicant (e.g., doxorobucin, daunorubicin, idarubicin, vincristine) and irritant (e.g., bendamustine, carmustine, oxaliplatin, etoposide, mitoxantrone) chemotherapeutic agents used in oncology and hematology. ● Table 3 in the original paper lists the main recommendations for managing antineoplastic extravasation. ○ In patients with extravasation of irritants with vesicant properties or vesicant antineoplastic agents, for all classes in which a pharmacologic antidote exists, ONS and ASCO recommend the use of antidotes rather than no antidotes ○ For patients with extravasation of irritants with vesicant properties or vesicant antineoplastic agents, Oncology Nursing Society (ONS) and American Society of Clinical Oncology (ASCO) suggest use of a thermal compress rather than no compress (choice of a warm or cold compress is dependent upon the agent that has extravasated). ■ Warm: vinca alkaloids, etoposide, oxaliplatin ■ Cold: alkylating agents (except oxaliplatin), anthracyclines, antimetabolites, taxanes (without hyaluronidase use). ○ For patients with extravasation of irritant with vesicant properties or vesicant antineoplastic agents, ONS and ASCO suggest a longer period of compress (repeated application over more than 24 hours) rather than a shorter period of compress (repeated application over 24 hours or less). ○ For patients with central line extravasation of irritant with vesicant properties or vesicant antineoplastic agents, ONS and ASCO suggest surgical referral/escalation of care in addition to conservative management rather than conservative management alone. High-risk populations—such as those receiving DNA-binding vesicants; those with high-volume estimated extravasation; and those with National Cancer Institute Common Terminology Criteria for Adverse Events grade 2 (erythema associated with symptoms such as edema, pain, induration, and phlebitis), grade 3 (ulceration or necrosis; severe tissue damage), or grade 4 (life-threatening consequences) extravasation— may have greater likelihood of benefiting from surgical referral/escalation in care. ● Table 4 in the original paper shows the antidotes used for management of antineoplastic extravasation. ○ Extravasation of anthracycline therapy = dexrazoxane. ○ Anthracycline extravasation when dexrazoxane is not available or is contraindicated = dimethyl sulfoxide. ○ Extravasation of vinca alkaloids = hyaluronidase. ○ Bendamustine extravasation = sodium thiosulfate. |
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A phase 2 trial of CHOP with anti-CCR4 antibody mogamulizumab for older patients with adult T-cell leukemia/lymphoma |
Highlights: ● No standard of care for older patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. ● This Japanese multicenter phase 2 trial evaluated the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 2 weeks with mogamulizumab (Moga; Moga-CHOP-14), for older patients with untreated ATL. ● Moga is a naked antibody that targets CC chemokine receptor 4 (CCR4), and binding to CCR4 on target cells can induce antibody-dependent cellular cytotoxicity. Moga-CHOP significantly improved 1-year progression-free survival (PFS) in older patients with CCR4-positive aggressive ATL. ● CCR4 mutations and Moga-associated cutaneous adverse events were related to better overall survival (OS). Patients aged ≥66 years and those aged 56 to 65 years ineligible for transplantation received 6 cycles of Moga-CHOP-14, followed by 2 cycles of Moga monotherapy. Among 48 evaluable patients, the 1-year PFS (primary outcome) was 36.2% (90% confidence interval, 24.9-47.6), with a median follow-up of 1.6 years. The 1-year OS and event-free survival were 66.0% and 29.9%, respectively. Complete response and overall response rate were 64.6% and 91.7%, respectively. No unexpected toxicities were observed. Although the optimal interval for CHOP remains undetermined, Moga-CHOP is now considered a preferable first-line treatment for this patient population. |
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Bleeding Patterns and Clinical Outcomes in Patients With Systemic AL Amyloidosis-Related Acquired Factor X Deficiency [Retrospective cohort] |
Highlights: ● Bleeding symptoms are frequent in light chain (AL) amyloidosis, and the underlying mechanisms include: increased vascular fragility and vasculopathy secondary to amyloid deposition; reduced coagulation factor production secondary to hepatic dysfunction; acquired von Willebrand syndrome; and acquired factor X (aFX; rare manifestation) deficiency attributed to adsorption of this coagulation factor onto amyloid fibril deposits. ● In this study the severity of aFX deficiency is not significantly associated with bleeding symptoms, highlighting the complexity of bleeding risk assessment in this population. ● The authors practice is to screen every patient for aFX deficiency irrespective of bleeding symptoms; to avoid the use of antiplatelet aggregation and anticoagulation agents; and to utilize higher thresholds for platelet transfusion during the period of thrombocytopenia during clone-directed therapies. ● Preventive and supportive measures— such as higher platelet transfusion thresholds, antifibrinolytics, fresh frozen plasma, prothrombin complex concentrates, or recombinant coagulation factors—are essential to minimize complications. Of 1956 patients (Boston University Amyloidosis Center between 2000 and 2023), 88 (4.4%) had aFX deficiency. Prior studies reported the prevalence of FX deficiency to range from 6% to 14% among patients with AL amyloidosis. FX activity showed a negative correlation with hepatic involvement (r = −0.291, p=0.006) and multi-organ disease (r = −0.239, p=0.025), indicating that a more severe aFX deficiency was associated with these clinical features. Conversely, FX activity showed a positive correlation with age at diagnosis (r=0.418, p<0.001), suggesting that younger patients were more likely to have more severe aFX deficiency. 56% (n=49/88) of patients reported at least one bleeding manifestation at or near the time of diagnosis, predominantly cutaneous. High-dose melphalan followed by autologous stem cell transplantation provides high rates and magnitudes of FX improvement but should be used carefully in selected patients, due to the risk of bleeding. |
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