Novelties on Multiple Myeloma from the Main 2024 Hematology Conferences.

Despite the introduction of several therapies in recent years, multiple myeloma (MM) remains a hematologic malignancy difficult to treat due to its extreme inter- and intra-patient heterogeneity. However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced diseases. Up-front quadruplet combinations, including anti-CD38 monoclonal antibodies, proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant-eligible and not-eligible patients with MRD assessment that could play a key role in determining the duration of therapy, avoiding unnecessary overtreatment.

Comparison of isatuximab-pomalidomide-dexamethasone elotuzumab-pomalidomidedexamethasone in relapsed/refractory multiple myeloma patients: a target trial emulation using real-world data.

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Long-Term Survival with Multiple Myeloma: An Italian Experience.

Background/objectives: Treatments for multiple myeloma (MM) have expanded in the last decade, and the overall survival (OS) of MM patients (pts) is in continuous improvement. With the availability of new treatments and the use of high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation (ASCT), the median OS of newly diagnosed MM (NDMM) pts is 6-8 years. To date, approximately 50% and 28% of MM patients are still alive at 5 years and 10 years.

Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab-Refractory Multiple Myeloma Patients: A Multicenter Real-World Study.

This multicenter real-world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple myeloma (MM) who were refractory to daratumumab (Dara-R). The majority were under 70 years old (60.8%), predominantly female (56.

Shaping the Future of Myeloproliferative Neoplasm Therapy: Immune-Based Strategies and Targeted Innovations.

Numerous cutting-edge immunotherapy approaches have been developed for hematological malignancies, such as immune-checkpoint inhibitors for lymphomas, chimeric antigen receptor (CAR)-T-cell treatments for B-cell cancers, and monoclonal antibody therapies for acute myeloid leukemia (AML). However, achieving similar breakthroughs in MPNs has proven challenging. The key obstacles include the absence of universally expressed and MPN-specific surface markers, significant cellular and molecular variability among both individual patients and across different MPN subtypes, and the failure of treatments to stimulate an anti-tumor immune response due to the immune system disruptions caused by the myeloid neoplasm.

A rare case of solitary plasmacytoma mimicking submucosal lesion of ascending colon: a case report and literature review.

Solitary primary extraosseous plasmacytoma is a rare disease in the gastrointestinal tract, recently classified as an "exceptional" tumor of the colon site. The real incidence (one case/population/year) is unknown but reasonably less than 1/10,000,000 cases/year with very few descriptions in the literature. The rare cases described in the literature are often diagnosed after surgery for perforation and with predominant localization of the left colon.

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.

The Challenging Approach to Multiple Myeloma: From Disease Diagnosis and Monitoring to Complications Management.

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment.

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.

Second Neoplasms in Italian Patients with Hairy Cell Leukemia after Treatment with Cladribine: A Multicenter Investigation and Literature Review.

Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.

Predictors of unsustained measurable residual disease negativity in patients with multiple myeloma.

The prognostic impact of achieving and in particular maintaining measurable residual disease (MRD) negativity in multiple myeloma is now established; therefore, identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter.

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.

High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma.

Purpose: High levels of circulating tumor plasma cells (CTC-high) in patients with multiple myeloma are a marker of aggressive disease. We aimed to confirm the prognostic impact and identify a possible cutoff value of CTC-high for the prediction of progression-free survival (PFS) and overall survival (OS), in the context of concomitant risk features and minimal residual disease (MRD) achievement.

Methods: CTC were analyzed at diagnosis with two-tube single-platform flow cytometry (sensitivity 4 × 10) in patients enrolled in the multicenter randomized FORTE clinical trial (ClinicalTrials.

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.