Explore the vast range of titles available.

Thalidomide plus dexamethasone (TD) is a standard induction therapy for myeloma. We aimed to assess the efficacy and safety of addition of bortezomib to TD (VTD) versus TD alone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma. Patients (aged 18–65 years) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May, 2006, and April, 2008, and data collection continued until June 30, 2010. Patients were randomly allocated (1:1 ratio) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily for the first 14 days and 200 mg daily thereafter) plus dexamethasone (40 mg daily on 8 of the first 12 days, but not consecutively; total of 320 mg per cycle), either alone or with bortezomib (1·3 mg/m 2 on days 1, 4, 8, and 11). The randomisation sequence was computer generated by the study coordinating team and was stratified by disease stage. After double autologous stem-cell transplantation, patients received two 35-day cycles of their assigned drug regimen, VTD or TD, as consolidation therapy. The primary endpoint was the rate of complete or near complete response to induction therapy. Analysis was by intention to treat. Patients and treating physicians were not masked to treatment allocation. This study is still underway but is not recruiting participants, and is registered with ClinicalTrials.gov, number NCT01134484, and with EudraCT, number 2005-003723-39. 480 patients were enrolled and randomly assigned to receive VTD (n=241 patients) or TD (n=239). Six patients withdrew consent before start of treatment, and 236 on VTD and 238 on TD were included in the intention-to-treat analysis. After induction therapy, complete or near complete response was achieved in 73 patients (31%, 95% CI 25·0–36·8) receiving VTD, and 27 (11%, 7·3–15·4) on TD (p<0·0001). Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD (n=132, 56%) than in those on TD (n=79, 33%; p<0·0001), with a higher occurrence of peripheral neuropathy in patients on VTD (n=23, 10%) than in those on TD (n=5, 2%; p=0·0004). Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD, and in three of five patients on TD. VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response, and represents a new standard of care for patients with multiple myeloma who are eligible for transplant. Seràgnoli Institute of Haematology at the University of Bologna, Bologna, Italy.

The introduction of chimeric antigen receptor T (CAR-T) cell and bispecific antibody (BsAb) therapies has revolutionized multiple myeloma (MM) treatment, offering exceptional efficacy, and culminating in recent regulatory approval. However, these therapies have brought unique toxicity challenges, manifesting not only with the well-established cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but also with the emergence of other common and equally distinctive toxicities, including cytopenias, hypogammaglobulinemia, infections, and the rare but life-threatening immune effector cell-like lymphohistiocytosis syndrome (IEC-HS). These adverse events are characterized by unique mechanisms of action that differ from those of previous treatments for MM, thereby requiring specialized knowledge to optimize day-to-day management and ultimately maximize therapeutic benefits while ensuring patient safety. Additionally, the toxicity profiles of these T-cell engager therapies are becoming increasingly important in treatment decisions, with implications for patient selection and therapy sequencing. In this review, we provide a comprehensive overview of the current state-of-the-art regarding the incidence, etiopathogenetic mechanisms, and clinical manifestations of these increasingly less non-prototypical but still lesser-known side effects than CRS and ICANS, in order to offer clear and actionable insights into their effective management, while emphasizing critical points for future improvement, in view of the increasing number of MM patients who will benefit from the newly approved and upcoming immunotherapies.

Objective Nocturnal hypoventilation (NH) is a complication of respiratory involvement in neuromuscular disorders (NMD) that can evolve into symptomatic daytime hypercapnia if not treated proactively with non-invasive ventilation. This study aimed to assess whether NH can be detected in the absence of other signs of nocturnal altered gas exchange. Methods We performed nocturnal transcutaneous coupled (tc) pCO2/SpO2 monitoring in 46 consecutive cases of paediatric-onset NMD with a restrictive respiratory defect (forced vital capacity < 60%). Nocturnal hypoventilation was defined as tcPCO2 > 50 mmHg for > 25% of recorded time, and hypoxemia as tcSpO2 < 88% for > 5 minutes. Daytime symptoms and bicarbonate were recorded after overnight monitoring. Results Twenty-nine of 46 consecutive patients showed NH. Twenty-three patients did not have nocturnal hypoxemia and 18 were clinically asymptomatic. In 20 patients, PaCO2 in daytime blood samples was normal. Finally, 13/29 patients with NH had isolated nocturnal hypercapnia without nocturnal hypoxia, clinical NH symptoms, or daytime hypercapnia. Conclusions Paediatric patients with NMD can develop NH in the absence of clinical symptoms or significant nocturnal desaturation. Therefore, monitoring of NH should be included among nocturnal respiratory assessments of these patients as an additional tool to determine when to commence non-invasive ventilation.

This systematic review examines the available clinical data on CD34+ cell mobilization, collection, and engraftment in multiple myeloma patients treated with the anti-CD38 monoclonal antibodies daratumumab and isatuximab in clinical trials and in real life. Twenty-six clinical reports were published between 2019 and February 2024. Most studies documented lower circulating CD34+ cells after mobilization compared to controls, leading to higher plerixafor requirements. Although collection yields were significantly lower in approximately half of the studies, the collection target was achieved in similar proportions of daratumumab- and isatuximab-treated and nontreated patients, and access to autologous stem cell transplant (ASCT) was comparable. This could be explained by the retained efficacy of plerixafor in anti-CD38 monoclonal antibody-treated patients, while no chemotherapy-based or sparing mobilization protocol proved superior. Half of the studies reported slower hematopoietic reconstitution after ASCT in daratumumab- and isatuximab-treated patients, without an excess of infectious complications. While no direct effect on stem cells was observed in vitro, emerging evidence suggests possible dysregulation of CD34+ cell adhesion after daratumumab treatment. Overall, anti-CD38 monoclonal antibodies appear to interfere with CD34+ cell mobilization, without consistently leading to significant clinical consequences. Further research is needed to elucidate the underlying mechanisms and define optimal mobilization strategies in this patient population.

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

Multiple myeloma (MM) is a plasma cell (PC) disorder characterized by skeletal involvement at the time of diagnosis. Recently, cell-free DNA (cfDNA) has been proven to recapitulate the heterogeneity of bone marrow (BM) disease. Our aim was to evaluate the prognostic role of cfDNA at diagnosis according to disease distribution, and to investigate the role of the MM microenvironment inflammatory state in supplying the release of cfDNA. A total of 162 newly diagnosed MM patients were screened using 18F-FDG PET/CT and assessed by ultra low-pass whole genome sequencing (ULP-WGS). High cfDNA tumor fraction (ctDNA) levels were correlated with different tumor mass markers, and patients with high ctDNA levels at diagnosis were more likely to present with metabolically active paraskeletal (PS) and extramedullary (EM) lesions. Moreover, we demonstrated that microenvironment cancer-associated fibroblast (CAFs)-mediated inflammation might correlate with high ctDNA levels. Indeed, a high cfDNA TF level at diagnosis predicted a poorer prognosis, independent of R-ISS III and 1q amplification; the inclusion of >12% ctDNA in the current R-ISS risk score enables a better identification of high-risk patients. ctDNA can be a reliable and less invasive marker for disease characterization, and can refine patient risk.

Objective The aim of this paper was to report the 2‐year follow‐up in type I patients treated with Nusinersen and to assess whether possible changes in motor function are related to the subtype, age, or SMN2 copy number. Methods Sixty‐eight patients, with ages ranging from 0.20 to 15.92 years (mean: 3.96; standard deviation: +3.90) were enrolled in the study. All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the developmental section of the Hammersmith Infant Neurological Examination (HINE‐2) at the time they started treatment and 12 and 24 months after that. Results For both CHOP and HINE‐2 repeated measures analysis of variance showed a significant difference (P < 0.001) between baseline and 12 months, 12 months and 24 months, and baseline and 24‐month scores for the whole group. When age subgroups (<210 days, <2 years, 2–4 years, 5–11 years, 12–18 years) were considered, on the CHOP INTEND the difference was significant between baseline and 24 months in all age subgroups. On the HINE‐2, the difference between baseline and 24 months was significant in all the subgroups before the age of 4 years. Age was predictive of changes on both scales (P < 0.05), whereas SMN2 copy number and decimal classification were not. Interpretation Our results suggest that some improvement of motor function can be observed even after the first year of treatment. This is more obvious in the infants treated in the first 2 years but some improvement can also be found in older children.

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients’ outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient’s outcome.