Breast Cancer With Release of Tumor Cells in Peripheral Blood Mimicking Acute Myeloid Leukemia.

A 75-year-old woman with a history of lobular breast adenocarcinoma treated with mastectomy and radiotherapy in 2021 and on maintenance hormone therapy, presented with asthenia and tremors. Laboratory tests showed leucocytosis, anemia and low platelet count, with increased serum calcium, lactate dehydrogenase and indirect bilirubin levels. Haptoglobin was decreased and renal function was normal.

Belantamab mafodotin in triple-refractory multiple myeloma patients: A retro-prospective observational study in Italy.

Belantamab mafodotin is the first-in-class antibody-drug conjugates targeting B-cell maturation antigen to have demonstrated effectiveness in triple-class refractory multiple myeloma (TCR-MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42-86 years), ECOG performance status was ≥1 in 45% of patients.

Belantamab Mafodotin: From Clinical Trials Data to Real-Life Experiences.

Despite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody-drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy.

Real-world assessment of treatment patterns and outcomes in patients with relapsed-refractory multiple myeloma in an Italian haematological tertiary care centre.

Despite significant improvements in therapeutic options, multiple myeloma (MM) patients experience a series of remissions and relapses requiring further lines of therapy (LOTs). We analysed treatment pathways, attrition rates (ARs) and refractoriness patterns across LOTs in 413 MM patients treated from 2011 and 2021. Across LOT-2 to LOT-5 ARs were 26%, 27%, 34% and 37.

Maintenance therapy in multiple myeloma: Two is not always better than one.

In multiple myeloma (MM) long-term therapy aims to control disease and delay progression for as long as possible. In this issue Jenner et al. failed to demonstrate a benefit of maintenance with lenalidomide plus vorinostat compared with lenalidomide in both transplant eligible (TE) and ineligible (NTE) patients enrolled in the Myeloma XI trial.

An update on novel multiple myeloma targets.

Introduction: Despite therapeutic progress, leading to a significant improvement of outcome, multiple myeloma (MM) remains a difficult to treat hematologic disease due to its biological heterogeneity and clinical complexity.

Areas Covered: Treatment of patients refractory and resistant to all classes of agents used in newly diagnosed MM is becoming a relevant problem for every hematologist. New generation immunotherapies, such as conjugated mAb, bispecific mAbs and CAR-T cells, targeting novel molecules as BCMA, have showed relevant results in very advanced MM.

Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS).

Belantamab Mafodotin for the Treatment of Multiple Myeloma: An Overview of the Clinical Efficacy and Safety.

Despite the introduction of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and, more recently, monoclonal antibodies (mAbs), in the chemotherapy regimens for newly diagnosed (NDMM) and relapsed/refractory MM (RRMM), the occurrence of drug resistance remains a challenge in MM patients. This is mainly in the advanced stage of the disease when treatments are limited, and the prognosis is abysmal. Nevertheless, novel molecules and therapeutic approaches are rapidly moving through the several phases of drug development and could address the need for new treatment options.

Novel Experimental Drugs for Treatment of Multiple Myeloma.

Multiple myeloma (MM) is the second most frequent hematological malignancy characterized by bone marrow aberrant plasma cells proliferation leading to a genetic complex and heterogeneous disease, with a median survival ranging from two to more than 10 years. By using new drugs such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs) in different combinations and high-dose therapy followed by auto-transplantation, there has been an amazing improvement in the outcome of this disease in recent years. Despite this, MM is still considered an incurable disease, characterized by remission periods alternated with relapse/progression episodes finally leading to resistant disease.

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments.

Immunotherapy is changing the paradigm of multiple myeloma (MM) management and daratumumab is the first-in-class human monoclonal antibody targeting CD38 approved for the treatment of this malignancy. Daratumumab exerts anti-myeloma activity by different mechanisms of action as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), direct apoptosis, and immunomodulation. After GEN501 and SIRIUS trials showed efficacy of daratumumab monotherapy in heavily pretreated relapsed-refractory multiple myeloma (RRMM), in patients with at least two previous line of therapy, two phase III trials demonstrated superior overall response rate (ORR) and progression free survival (PFS) using triplets daratumumab-bortezomib-dexamethasone (DVd) Vd (CASTOR) or daratumumab-lenalidomide-dexamethasone (DRd) Rd (POLLUX) in relapsed-refractory MM patients; so these combinations have been approved and introduced in clinical practice.

Monoclonal Antibodies: Leading Actors in the Relapsed/Refractory Multiple Myeloma Treatment.

Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and daratumumab, directed against CD38, in combination with Rd and with bortezomib and dexamethasone (Vd), have been approved for the treatment of relapsed/refractory MM (RRMM) after they demonstrated excellent efficacy.

Developments in consolidation and maintenance strategies in post-remission multiple myeloma.

: Multiple Myeloma (MM) is a very heterogeneous clonal plasma cell hematological malignancy for which new therapies and transplantation effectively improve Progression-free survival (PFS) and overall survival (OS). Maintenance seems to have made a significant contribution in achieving these advances, whereas the real role of consolidation is still controversial. Despite lenalidomide having been approved as maintenance therapy after autologous stem cell transplantation (ASCT), the optimal maintenance agent, drug combinations, schedules, and duration are still under investigation.

Triplet vs. doublet drug regimens for managing multiple myeloma.

Introduction: Multiple Myeloma (MM) is a complex and heterogeneous plasma cell disorder. Sub-clones present before therapy and clonal evolution during therapy make this disease more resistant and finally refractory. These findings make us aware of the difficulty to target MM with few agents.

A review discussing elotuzumab and its use in the second-line plus treatment of multiple myeloma.

Monoclonal antibodies (mAb) represent a new frontier to treat newly diagnosed and relapsed-refractory multiple myeloma (MM). Elotuzumab, an mAb targeted SLAM7 in the plasma cells and natural killer cells surface, is the first mAb approved for the treatment of relapsed-refractory MM in combination with lenalidomide and dexamethasone. This approval was the final result of several preclinical and Phase I-II clinical studies leading to ELOQUENT-2 Phase III trial that demonstrated that elotuzumab adds a significant and durable value to standard therapy, paved the way of this new treatment strategy for MM.

Stem Cell Transplantation in Multiple Myeloma.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients younger than 65 years of age with multiple myeloma (MM). However, this therapeutic approach has undergone substantial advances in this last decade, mainly due to the introduction of new drugs such as thalidomide, lenalidomide and bortezomib. These new drugs, in different combinations, have shown to significantly increase response rates after induction therapy and ASCT.

Oral ixazomib maintenance therapy in multiple myeloma.

Continuous therapy has proven to be an effective therapeutic strategy to improve the outcome of both young and elderly multiple myeloma patients. Remarkably, lenalidomide and bortezomib showed to play a crucial role in this setting due to their safety profile allowing long-term exposure. Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy.

Ixazomib for the treatment of multiple myeloma.

Introduction: Proteasome inhibition is a mainstay in the treatment of multiple myeloma (MM). Bortezomib, the first proteasome inhibitor (PI) approved for MM therapy, has shown efficacy in relapsed/refractory patients and in the front-line setting. Among second-generation PIs, MLN9708 ( ixazomib ) is the first oral compound to be evaluated in MM treatment and has shown improvement in pharmacokinetic and pharmacodynamic parameters compared with bortezomib with a similar efficacy in the control of myeloma growth and in the prevention of bone loss.

Smoldering multiple myeloma: to treat or not to treat.

Introduction: Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥ 30 g/l serum M-protein and/or ≥ 10% bone marrow plasma cell infiltration. The progression risk to active multiple myeloma (MM) is not uniform, and several prognostic parameters are useful for identifying patients at high risk of progression. A watch-and-wait approach has been the standard of care up to now.

An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma.

Proteasome inhibition represents one of the more important therapeutic targets in the treatment of multiple myeloma (MM), since by suppressing nuclear factor-κB activity, which promotes myelomagenesis, it makes plasma cells susceptible to proapoptotic signals. Bortezomib, the first proteasome inhibitor approved for MM therapy, has been shown to increase response rate and improve outcome in patients with relapsed/refractory disease and in the frontline setting, particularly when combined with immunomodulatory drugs and alkylating agents. Among second-generation proteasome inhibitors, ixazomib (MLN9708) is the first oral compound to be evaluated for the treatment of MM.