Revised "iRR6" model in intermediate-1 risk myelofibrosis patients treated with ruxolitinib.

Background: The response to ruxolitinib after 6 months (RR6) model allows early identification of ruxolitinib-treated myelofibrosis (MF) patients with poorer overall survival (OS); however, it is less applicable to lower-risk patients.

Methods: To further explore this, the authors performed a subanalysis of the "RUX-MF" study (NCT06516406) with an aim to validate the RR6 and to develop a score specific for intermediate-1 DIPSS/MYSEC-PM risk patients.

Results: Among the 776 evaluable patients, 34.

Bortezomib-melphalan-prednisone versus lenalidomide-dexamethasone in elderly patients with multiple myeloma: the Real MM phase IV trial.

Not available.

Carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial.

Background: Before the introduction of daratumumab-lenalidomide-dexamethasone as a first-line treatment for patients with newly diagnosed transplant-ineligible multiple myeloma, lenalidomide-dexamethasone was a standard of care. We aimed to explore whether addition of the second-generation proteasome inhibitor carfilzomib to lenalidomide-dexamethasone improved the rates of measurable residual disease (MRD) negativity and progression-free survival.

Methods: EMN20 is a randomised, open-label, multicentre, phase 3 trial comparing weekly carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed transplant-ineligible multiple myeloma, conducted in 27 centres in Italy.

Exploring thromboembolic risk factors in polycythemia vera: from current evidence to PROSPERO study design.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm with a substantial risk of thromboembolic events (TEs), which contribute to morbidity and mortality. Traditional thrombotic risk stratification primarily considers age and thrombosis history, yet these parameters alone do not capture the complexity of thrombotic risk. Growing evidence highlights the role of additional factors influencing the risk of TEs, underscoring the need for a more comprehensive approach to patient stratification.

Impact of ELN clinical signs and symptoms on the thrombotic risk in polycythemia vera patients treated with front-line hydroxyurea.

The European LeukemiaNet recently proposed specific Clinical Signs and Symptoms (CSSs) that may trigger cytoreduction in patients with polycythemia vera (PV) at low thrombotic risk (LR). To evaluate the impact of CSSs on the thrombotic risk of patients at LR, high risk by age only (HR-AGE) or by previous thrombosis (HR-THRO), we conducted a multicenter cooperative study (NCT06134102) involving 739 PV patients treated with first-line hydroxyurea. At hydroxyurea start, 443 patients had at least one CSS.

Disease Phenotype Significantly Influences the Outcome After Discontinuation of Ruxolitinib in Chronic Phase Myelofibrosis.

Introduction: In patients with myelofibrosis (MF), overall survival (OS) after ruxolitinib discontinuation is poor, with leukemic transformation, clonal evolution and thrombocytopenia as the main factors worsening prognosis.

Patients And Methods: To assess the impact of disease phenotype on outcome after ruxolitinib discontinuation in chronic phase patients, we performed a sub-analysis of the "RUX-MF" study (NCT06516406), which now includes 1055 MF patients who received ruxolitinib in a real-life context.

Results: After a median follow-up of 3.

Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI).

Background: Myelofibrosis (MF) significantly impacts patients' overall survival (OS) and quality of life (QOL). This prospective study analyzed ruxolitinib dosing patterns and associated clinical outcomes in patients with MF over 12 months.

Methods: ROMEI, a multicenter, observational, ongoing study, enrolled 508 adult patients with MF treated with ruxolitinib.

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single-arm FIL-BRB trial.

This multicentre phase II study Fondazione Italiana Linfomi (FIL)-bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m on days 1-2), rituximab (375 mg/m intravenously on day 1) and bortezomib (1.3 mg/m sc on days 1, 8, 15, 22) every 28 days for six cycles in 38 symptomatic patients with relapsed/refractory Waldenstrom macroglobulinaemia (RR-WM). Moreover, MYD88 and CXCR4 mutations were tested by droplet digital polymerase chain reaction (ddPCR) both at baseline and at the end of treatment in 21 patients.

Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera.

BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2 open-label randomized trial, we compared ropeginterferon alfa-2b (ropeg; 100 μg every 2 weeks) with phlebotomy only regarding maintenance of a median hematocrit level (≤45%) over 12 months in the absence of progressive disease (primary end point). In follow-up, crossover to the alternative treatment group was allowed if the primary end point was not met.

Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs.

Diagnosis and Management of Cardiovascular Risk in Patients with Polycythemia Vera.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by aberrant myeloid lineage hematopoiesis with excessive red blood cell and pro-inflammatory cytokine production. Patients with PV present with a range of thrombotic and hemorrhagic symptoms that affect quality of life and reduce overall survival expectancy. Thrombotic events, transformation into acute myeloid leukemia, and myelofibrosis are largely responsible for the observed mortality.

Report of consensus Panel 4 from the 11th International Workshop on Waldenstrom's macroglobulinemia on diagnostic and response criteria.

Consensus Panel 4 (CP4) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with reviewing the current criteria for diagnosis and response assessment. Since the initial consensus reports of the 2nd International Workshop, there have been updates in the understanding of the mutational landscape of IgM related diseases, including the discovery and prevalence of MYD88 and CXCR4 mutations; an improved recognition of disease related morbidities attributed to monoclonal IgM and tumor infiltration; and a better understanding of response assessment based on multiple, prospective trials that have evaluated diverse agents in Waldenstrom's macroglobulinemia. The key recommendations from IWWM-11 CP4 included: (1) reaffirmation of IWWM-2 consensus panel recommendations that arbitrary values for laboratory parameters such as minimal IgM level or bone marrow infiltration should not be used to distinguish Waldenstrom's macroglobulinemia from IgM MGUS; (2) delineation of IgM MGUS into 2 subclasses including a subtype characterized by clonal plasma cells and MYD88 wild-type, and the other by presence of monotypic or monoclonal B cells which may carry the MYD88 mutation; and (3) recognition of "simplified" response assessments that use serum IgM only for determining partial and very good partial responses (simplified IWWM-6/new IWWM-11 response criteria).

Report of Consensus Panel 6 from the 11 th International Workshop on Waldenström's Macroglobulinemia on Management of Waldenström's Macroglobulinemia Related Amyloidosis.

Consensus Panel 6 (CP6) of the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM-11) was tasked with reviewing the state of the art for diagnosis, prognosis, and therapy of AL amyloidosis associated with Waldenström macroglobulinemia (WM). Since significant advances have been made in the management of AL amyloidosis an update for this rare disease associated with WM was necessary. The key recommendations from IWWM-11 CP6 included: (1) The need to improve the diagnostic process by recognizing red flags and using biomarkers and imaging; (2) The essential tests for appropriate workup; (3) The diagnostic flowchart, including mandatory amyloid typing, that improves the differential diagnosis with transthyretin amyloidosis; (4) Criteria for therapy response assessment; (5) State of the art of the treatment including therapy of wild type transthyretin amyloidosis associated with WM.