A rare extra- and intracranial mixed vascular malformation involving the scalp soft tissues and the dura mater, associated with skull erosion, and characterized by both a low-flow capillary-venous component and a high-flow component consistent with a dural arteriovenous fistula involving a diploic vein, represents a complex therapeutic challenge. An 18-year-old man underwent multimodal imaging for evaluation of non-disabling headaches and intermittent pulsatile sensation. MRI and CT demonstrated focal calvarial erosion, while MRA and digital subtraction angiography revealed a direct shunt between the middle meningeal artery and a diploic vein, in addition to a diffuse low-flow capillary-venous network supplied by branches of the external carotid artery and the middle meningeal artery. Treatment consisted of selective embolization of the shunt using n-butyl cyanoacrylate, followed by intra-arterial bleomycin administration combined with reversible electroporation targeting the slow-flow component. At 6-month follow-up, the patient was asymptomatic, with only localized alopecia at electrode application sites. Follow-up MRI demonstrated near-complete resolution of the dural component and marked reduction of the extracranial lesion, indicating a favorable clinical and radiological outcome.
Abstract Introduction: In RRMM, increasing rates of pt attrition and decreasing durability of responses with each line of therapy (LOT) necessitate early treatment (tx) with the most effective therapies. Immunotherapies that are widely accessible across different MM tx settings have the potential to change the trajectory of RRMM. Teclistamab (Tec), the first approved BCMA×CD3 bispecific antibody (BsAb) for heavily pretreated RRMM, provided deep, durable responses in MajesTEC-1, with improved efficacy and safety in earlier LOTs. Daratumumab (Dara), a standard-of-care (SoC) foundational CD38 targeted therapy with direct on-tumor activity, has been shown to deplete immunosuppressive T-cells and expand cytotoxic T-cells, creating an immune-permissive microenvironment for synergistic Tec-mediated killing of MM cells. MajesTEC-3 (NCT05083169) evaluates Tec-Dara vs SoC DPd/DVd in RRMM. We report initial results for this first phase 3 study of BsAb therapy in MM. Methods: Eligible pts had 1-3 prior LOTs including a PI and lenalidomide (Len; pts with 1 prior LOT must have been Len-refractory) with progressive disease (PD) on or after the last LOT. Pts with prior BCMA-directed therapy or refractory to anti-CD38 were excluded; prior anti-CD38 exposure was permitted. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. The Tec-Dara group received 28-day cycles (C) of Tec (1.5 mg/kg QW in C1-2 [C1 preceded by the approved step-up dose schedule]; 3 mg/kg Q2W in C3-6; and 3 mg/kg Q4W in C7+) with Dara; steroids were not required after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. Progression-free survival (PFS) by IRC was the primary endpoint; secondary endpoints included complete response or better (≥CR), overall response, minimal residual disease (MRD) negativity (10–5; next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety. Results: 587 pts were randomized (Tec-Dara, n=291; DPd/DVd, n=296). Median (range) age was 64 (25-88) yrs, median number of prior LOTs was 2 (1-3). With 34.5-mo median follow-up, Tec-Dara significantly improved PFS vs DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P<0.0001); mPFS was NR and 18.1 mo, and 36-mo PFS rate was 83.4% and 29.7%, respectively. PFS benefit was consistent across all prespecified and clinically relevant pt subgroups, including age ≥75 yrs, Len-refractory, high-risk cytogenetics, ≥60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposed. Significantly higher rates of ≥CR (81.8% vs 32.1%; OR, 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68-4.18), and MRD-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53-10.15) were observed with Tec-Dara (P<0.0001). There were 45 deaths with Tec-Dara and 96 with DPd/DVd, primarily due to PD (4.6%; 20.3%). OS significantly favored Tec-Dara (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001), including across all prespecified subgroups. The 36-mo OS rates were 83.3% and 65.0%, respectively and >90% of Tec-Dara pts alive at 6 mo were also alive at 30 mo. Median time to worsening of MM symptoms was NR with Tec-Dara vs 39.9 mo with DPd/DVd (HR, 0.50; 95% CI, 0.34-0.72; P=0.0002). At data cutoff, 49.4% of pts remained on study tx (Tec-Dara, 71.0%; DPd/DVd, 28.3%). Median tx duration was twice as long with Tec-Dara vs DPd/DVd (32.4 vs 16.1 mo). Frequency of grade 3/4 (Tec-Dara, 95.1%; DPd/DVd, 96.6%) and grade 5 (7.8%; 6.2%) treatment-emergent adverse events (TEAEs), were comparable (safety set: Tec-Dara, n=283; DPd/DVd, n=290). Serious TEAEs occurred in 70.7% Tec-Dara and 62.4% DPd/DVd pts; tx discontinuations due to TEAEs were low (4.6% vs 5.5%). Any grade infections occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd pts, respectively; grade 3/4 infections occurred in 54.1% and 43.4%. New onset grade ≥3 infections decreased over time, coinciding with transition to Q4W dosing and supported by antimicrobial and Ig prophylaxis guidance. CRS rate was 60.1% (grade 1/2: 44.2%/15.9%) and ICANS was 1.1% with Tec-Dara. Conclusion: We demonstrate the clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs. Infections with Tec-Dara were well managed with established protocols. This highly effective, off-the-shelf, immunotherapy combination represents a new SoC for RRMM as early as first relapse.
This multisociety, multidisciplinary consensus—formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology—was developed to standardise the assessment of ablation margins in liver tumour thermal ablation. A modified Delphi process, consisting of two online surveys and a hybrid (online and in-person meeting in Innsbruk) consensus meeting of 72 experts from North America, South America, Europe, and Asia. Formal consensus was reached for 150 (75%) of 199 statements. Strong agreement was observed between interventional and surgical oncologists, with only 12 (6%) of 199 statements showing significantly different ratings. Participants agreed that ablation margins should be assessed and documented for every treated tumour. Margins should be assessed quantitatively in three dimensions, with contrast-enhanced CT or MRI, preferably intraprocedurally with ablation confirmation software. Ablation margins should be categorised as A0 (tumour completely covered with sufficient margin), A1 (tumour completely covered but insufficient margin), or A2 (portion of tumour remains unablated). This effort is, to our knowledge, the first international consensus initiative to define best-practice recommendations for margin assessment in liver tumour thermal ablation to standardise practices, aiming to improve and promote uniform outcomes.
Most patients with large B-cell lymphoma (LBCL) progressing after CAR-T therapy experience poor survival and lack standardized treatment strategies. Prognostic tools are needed to guide decision-making at relapse. The Post-CAR Prognostic Index (PC-PI), recently proposed by Iacoboni et al., combines five routine clinical variables to stratify outcomes after CAR-T failure: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to progression (< 4 months). We evaluated the PC-PI in a retrospective multicenter study including 125 LBCL patients relapsing or refractory after axicabtagene-ciloleucel or tisagenlecleucel, treated between 2019 and 2023 across 16 Italian centers belonging to the Fondazione Italiana Linfomi network. Median overall survival (OS) was 4.9 months, with 6- and 12-month OS rates of 44.9% and 28.5%, respectively. The PC-PI discriminated prognosis effectively: high-risk patients had a median OS of 1.8 months, intermediate-high 2.2, intermediate-low 8.7, while in the low-risk group median OS was not reached (p<0.0001). Results remained consistent after excluding patients receiving only palliative care. Post-progression therapy markedly influenced survival: patients receiving active treatment achieved a median OS of 7.3 months versus 0.7 without further therapy (p<0.0001). Bispecific antibodies conferred the best outcomes (HR 0.44, p=0.02), with 6- and 12-month OS rates of 90% and 55%. Our findings confirm the prognostic value of the PC-PI and support its use in clinical practice as a tool for risk-adapted management of LBCL after CAR-T failure.
OBJECTIVE:To assess efficacy of voclosporin (VCL) from a retrospective, observational, clinical-practice-based, nationwide multicentre study of patients with LN. METHODS:Patients with biopsy-proven LN were enrolled from November 2023 to April 2025 from tertiary Rheumatology and Nephrology Italian Centres. Those with uncontrolled arterial hypertension and eGFR < 30 ml/min/1.73 m2 were excluded. Patients received oral 23.7 mg VCL BID and MMF 1 g BID. Glucocorticoid schedule followed existing recommendations for LN management. Clinical and serological data were collected at SLE diagnosis, VCL initiation and after 6, 12, 24 and 48 weeks. Complete renal response (CRR) was defined as eGFR ≥ 60 ml/min/1.73 m2, <20% eGFR decrease from baseline, 24-h proteinuria <0.5 g/day, no rescue therapy, prednisone ≤5 mg/day and partial renal response (PRR) as a 50% decrease of 24 h proteinuria and <20% eGFR decrease. RESULTS:Forty-two patients from 14 centres were enrolled, 26 females (61.9%), mean age 43.1 ± 11.9 years, follow-up 6.6 ± 5.1 months. A total of 31.5% of patients achieved CRR or PRR at 6 weeks, 68.9% at 12 weeks, 83.3% at 24 weeks and 91.6% at 48 weeks of follow-up. A significant decrease in 24-h proteinuria was observed at 6 weeks (P = 0.006) and at all subsequent time points. A mild eGFR decrease was observed at 6 (P = 0.008) and 24 weeks (P = 0.01), but not at 48 weeks. Significant decrease was also observed in anti-dsDNA positivity at 6 (P = 0.0016) and 12 weeks (P = 0.0009), and in SLEDAI-2K after 24 (P = 0.008) and 48 weeks (P = 0.05). CONCLUSIONS:VCL may provide a valuable therapeutic option in LN management, achieving early 24 h-proteinuria response consistent with clinical trial data.
