Pomalidomide, Cyclophosphamide, and Dexamethasone for Relapsed/Refractory Multiple Myeloma: A Single-Center Experience.

Introduction: Pomalidomide, a third-generation IMiD, has shown efficacy in relapsed/refractory multiple myeloma (RRMM). The addition of cyclophosphamide to pomalidomide and dexamethasone (PCd) has been explored as a potential therapeutic option in this challenging setting.

Methods: We conducted a retrospective analysis of RRMM patients treated with PCd in the Department of Clinical Therapeutics, Athens, Greece.

Prevention and treatment of venous thromboembolism in patients with multiple myeloma: Clinical practice guidelines on behalf of the European Myeloma Network.

Venous thromboembolism (VTE) is a frequent complication in patients with multiple myeloma (MM) that leads to increased morbidity, mortality, treatment interruptions, and reduced quality of life. Αn Expert Panel Consensus Guideline on behalf of the European Myeloma Network provides evidence-based recommendations for VTE prevention and treatment in patients with MM. Key recommendations include the following: .

Serum Proteomics of Ribociclib-Mediated Cardiovascular Toxicity: An Exploratory Case-Control Study.

Cyclin-dependent kinase 4/6 inhibitors have transformed hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC) therapeutics. Ribociclib has been associated with survival gain, yet its potential cardiovascular toxicities (CVTs) remain an area of uncertainty. Our single-center study prospectively recruited adult patients in order to assess treatment-related CVT incidence and spectrum as well as decipher proteins' differential expression in affected patients by data-independent acquisition liquid chromatography-tandem mass spectrometry (DIA LC-MS/MS).

Proteomic Analysis of Bone Marrow CD138+ Cells to Identify Proteins Associated With the Response of Multiple Myeloma Patients to Commonly Used Therapeutic Regimens.

Multiple myeloma (MM) remains incurable; gaps in our understanding of MM molecular pathogenesis and drugs' resistance mechanisms are involved in the failure of therapies. This study aims to identify proteins significantly impacting MM patients' response to commonly used therapeutic regimens. Bone marrow CD138+ selected plasma cells were isolated from patients who had achieved Response (Responders, R) and those who were Non-Responders (NR) to their primary MM therapy.

Modification of Belantamab Mafodotin Dosing to Balance Efficacy and Tolerability in the DREAMM-7 and DREAMM-8 Trials.

Belantamab mafodotin (belamaf) combined with standard therapies demonstrated significant progression-free survival (PFS) and overall survival benefits in DREAMM-7 and PFS benefit in DREAMM-8 in relapsed/refractory multiple myeloma. Belamaf dose modifications managed adverse events, including belamaf-related ocular events. Ocular events included ocular adverse reactions (eg, dry eyes, photophobia, eye irritation) and protocol-mandated ophthalmic examination findings.

Practical Guidance on Clinical Management of Belantamab Mafodotin-Associated Ocular Events.

Importance: Belantamab mafodotin (belamaf)-containing regimens are effective treatment options for patients with relapsed and/or refractory multiple myeloma. Ocular events are a common adverse effect of belamaf treatment, which can be managed by physicians, following appropriate training, to minimize their impact on the patient.

Objective: To develop clinical recommendations for the identification, monitoring, and management of ocular events associated with belamaf therapy, and guidance for any required dose modification.

Determinants of 15-Year Progression-Free Survival in Multiple Myeloma; Real-World Data From a Single Institution.

The therapeutic advances during the last two decades have rendered multiple myeloma a chronic disease and, thus, it is important to identify patient subgroups which may have extremely favorable outcomes and optimize their treatment. The current study aimed to evaluate the clinical and disease characteristics of patients with very long follow-up (minimum 15 years), to identify those with very long survival (> 15 years) and those with very long disease remissions (> 15 years) after frontline treatment diagnosed at a single center from 1994 to 2009. Among 323 consecutive, unselected patients, the calculated 15-year and 20-year cumulative survival rates were 18% and 14%, respectively.

Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial.

Background: In the primary (first interim) analysis of the DREAMM-7 trial (median follow-up 28·2 months), belantamab mafodotin, bortezomib, and dexamethasone (BVd) showed a statistically significant and clinically meaningful progression-free survival benefit versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM) after at least one line of therapy. The aim of this study is to report overall survival from the second interim analysis, with extended follow-up.

Methods: In the ongoing global, open-label, randomised, phase 3 DREAMM-7 trial done at 142 study centres (research facilities, hospitals, and institutions) in 20 countries across North America, South America, Europe, and the Asia-Pacific region, eligible patients were aged at least 18 years and had confirmed multiple myeloma (according to International Myeloma Working Group criteria), an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and progression on or after at least one previous line of therapy.

Isatuximab for the treatment of multiple myeloma: current clinical advances and future directions.

Introduction: The addition of the anti-CD38 monoclonal antibody isatuximab to standard therapies is transforming the care of patients with newly diagnosed multiple myeloma (NDMM), as previously seen in the relapsed/refractory setting. This is particularly important for patients with NDMM as early treatment with effective, well tolerated therapies may ensure better clinical outcomes.

Areas Covered: Here, we examine recent results from pivotal Phase 3 and 2 clinical trials that demonstrate efficacy and safety of isatuximab across multiple combinations, for both transplant-ineligible and transplant-eligible NDMM patients.

EHA-EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma.

Since the publication in 2021 of the European Hematology Association (EHA) Clinical Practice Guidelines for the treatment of patients with smouldering multiple myeloma (SMM) and multiple myeloma (MM), developed in collaboration with the European Society for Medical Oncology, a novel international staging system (R2-ISS) has been developed, several prognostic factors are entering clinical practice (such as minimal residual disease, circulating plasma cells and monoclonal protein assessed by mass spectrometry) and, at the time of writing, 14 novel regimens have been approved by the EMA and/or the FDA for the treatment of patients with MM. A multidisciplinary group of experts from the EHA and European Myeloma Network, based in various institutions mostly located in Europe, have updated the previous guidelines and produced algorithms for everyday clinical practice that incorporate levels of evidence and grades of recommendation based on the aforementioned new data. In these Evidence-Based Guidelines, we provide key treatment recommendations for both patients with newly diagnosed MM and those with relapsed and/or refractory MM, including guidance for the use of established drugs as well as contemporary immunotherapies.

Optimising T-cell immunotherapy in patients with multiple myeloma: practical considerations from the European Myeloma Network.

Novel T-cell immunotherapies (chimeric antigen receptor [CAR] T cells and T-cell redirecting bispecific antibodies) are changing the treatment landscape of relapsed or refractory multiple myeloma. In this Review, the European Myeloma Network provides recommendations to optimise both safety and efficacy of T-cell immunotherapy. In patients who are eligible for both CAR T-cell therapy and bispecific antibodies, we recommend using CAR T-cell therapy first due to the high response rate and durable progression-free survival, accompanied by improved quality of life.

Enhanced Risk Stratification of Smoldering Multiple Myeloma with Dynamic Biomarkers: A Multinational, Multicenter Study including 2,270 Participants (PANGEA 2.0).

Accurate prediction of risk of progression from smoldering (SMM) to active multiple myeloma (MM) is paramount to individualized early therapeutic strategies with minimum risk of overtreatment. Current risk stratification models do not account for evolving biomarker trajectories. We assembled the largest cohort to date of 2,270 SMM patients from six international centers with longitudinal clinical and biological data to train and validate the PANGEA 2.

Report of Consensus Panel 3 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with high-risk disease.

The Consensus Panel 3 (CP3) of the 12th International Workshop on Waldenström macroglobulinemia (IWWM-12) has reviewed and incorporated current data to make recommendations for the management of patients with high-risk WM (HR-WM). Recognizing the considerable heterogeneity in survival outcomes and identifying a subgroup of patients with a very poor prognosis, the key recommendations from CP3 include: (1) Risk stratifying patients with smoldering WM (SWM) and active (symptomatic) WM at diagnosis (2) Using the degree of i) bone marrow lymphoplasmacytosis, ii) serum beta-2 microglobulin (β2M) elevation, iii) IgM increase, iv) serum albumin decrease and the presence of wild-type MYD88 status markers that adversely dictate the time-to-progression from smoldering to active WM to the define HR-SWM. (3) Among patients with active WM, the presenting parameters: advanced chronological age, low serum albumin, elevated serum lactate dehydrogenase, elevated β2M and the presence of TP53 alterations (TP53 mutation or deletion 17p) unfavorably impact the prognosis and should be utilized to risk-stratify patients into the HR category.

Report of Consensus Panel 1 from the 12th International Workshop on the management of patients with IgM and Waldenstrom's Macroglobulinemia related neuropathy.

The IgM-related peripheral neuropathies (IgM-PN) are a group of chronic disorders characterized by the presence of monoclonal IgM that may be associated with one of several diseases affecting the peripheral nerves. In many cases, there is a monoclonal IgM associated with activity against neural targets, leading to progressive peripheral nerve demyelination. Neurological symptoms in this setting can also result from direct invasion of the peripheral or central nervous system by lymphoplasmacytic cells (neurolymphomatosis and Bing-Neel syndrome respectively) or via other mechanisms (for example AL amyloid deposition or cryoglobulinemic vasculitis).

Immunotherapy in primary hormone-receptor positive breast cancer: A systematic review.

Hormone-receptor positive (HR+), HER2 negative breast cancer (BC) is considered immunologically silent, thus investigation of immunotherapy in this subtype has evolved slower. This systematic review offers an overview of the clinical trials investigating the safety and efficacy of ICI in primary HR+ /HER2- BC. Literature search was conducted up to October 30, 2022 to identify immunotherapy trials with checkpoint inhibitors in non-metastatic HR+ /HER2- breast cancer.

Genomic landscape of multiple myeloma and its precursor conditions.

Reliable strategies to capture patients at risk of progression from precursor stages of multiple myeloma (MM) to overt disease are still missing. We assembled a comprehensive collection of MM genomic data comprising 1,030 patients (218 with precursor conditions) that we used to identify recurrent coding and non-coding candidate drivers as well as significant hotspots of structural variation. We used those drivers to define and validate a simple 'MM-like' score, which we could use to place patients' tumors on a gradual axis of progression toward active disease.

Report of Consensus Panel 5 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with intolerance or resistance to covalent BTK inhibitors.

Over the last decade, covalent Bruton tyrosine kinase (BTK) inhibitors have become a standard option for treating patients with symptomatic Waldenström Macroglobulinemia (WM) in the frontline or relapsed settings. However, the definition of intolerance and resistance to covalent BTK inhibitors has not been established. Understanding the best approaches to managing such patients is crucial to avoiding premature abandonment of effective therapy or pursuing futile therapies unlikely to be effective in controlling symptomatic disease progression.

Daratumumab for newly diagnosed multiple myeloma: Pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS.

Background: Older adults with newly diagnosed multiple myeloma (NDMM) have poor prognosis and constitute a subgroup of particular interest. In the GRIFFIN (NCT02874742) and PERSEUS (NCT03710603) studies, adding daratumumab to bortezomib/lenalidomide/dexamethasone (VRd) induction/consolidation and lenalidomide (R) maintenance deepened responses and improved progression-free survival (PFS) versus VRd/R in transplant-eligible patients with NDMM. Subgroup analyses of patients aged ≥65 years in PERSEUS demonstrated less pronounced PFS benefits (HRs: 0.

EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma.

Multiple myeloma (MM) is a plasma cell neoplasm that stems from the malignant transformation of clonal plasma cells. It is characterized by multiple periods of remission and relapse requiring multiple lines of therapy, with response to treatment and survival decreasing with each successive relapse. To achieve deep and durable responses in relapsed/refractory MM (RRMM), novel treatments are required.

A prospective study of small fiber neuropathy in AL amyloidosis.

The peripheral nervous system (PNS) is commonly affected in immunoglobulin light chain amyloid protein (AL) amyloidosis. PNS involvement and particularly small fiber neuropathy (SFN) is often clinically underestimated, requiring a standardized approach for comprehensive assessment. We prospectively evaluated the prevalence and clinical significance of SFN in 81 patients with newly diagnosed AL amyloidosis using clinical examination, nerve conduction studies (NCSs), quantitative sensory testing (QST) examination and distal-leg skin biopsy.

Predictive value of free light chain burden in patients with AL amyloidosis treated with bortezomib-based regimens.

A difference between involved and uninvolved free light chains (dFLC) ≥180 mg/L is part of the 2012 Mayo staging system for amyloid light chain (AL) amyloidosis given its negative impact on overall survival (OS). However, none of the 758 patients evaluated to develop and validate this staging system received bortezomib or daratumumab-containing regimens. Over the past 2 decades, cyclophosphamide-bortezomib-dexamethasone (CyBorD) and, more recently, daratumumab-CyBorD (DaraCyBorD) have become cornerstone treatments for AL amyloidosis, demonstrating high efficacy in rapidly normalizing FLC levels.

A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma.

Modakafusp alfa is a first-in-class immunocytokine-directing interferon alfa to CD38+ cells. Our previous phase 1/2 trial identified 2 potential phase 2 doses of modakafusp alfa for patients with relapsed/refractory multiple myeloma (RRMM): 1.5 or 3 mg/kg every 4 weeks.

Efficacy and safety of isatuximab monotherapy to treat relapsed or refractory multiple myeloma: a pooled analysis of clinical trials.

This pooled analysis of phase 1 and 2 clinical trials evaluated the efficacy and safety of isatuximab as monotherapy in individuals with relapsed or refractory multiple myeloma (RRMM) who had previously received a median of 4.0 lines of therapy; safety data for individuals on isatuximab plus dexamethasone has also been evaluated. The efficacy analysis (n = 167) showed that isatuximab 20 mg/kg monotherapy was effective in the treatment of individuals with RRMM, with an overall response rate (ORR) of 26.