Experts' consensus on the definition and management of high risk multiple myeloma.

High risk multiple myeloma (HRMM) at diagnosis is currently recognized according to the Revised International Staging System (R-ISS) which was set up in 2015. Since then, new clinical and biological prognostic factors have been developed, which could implement the definition of High Risk (HR) category. We conducted a survey in order to identify which additional parameters, both clinical and biological, are considered more useful for the clinical practice and to evaluate if the management of Multiple Myeloma (MM) should change on the basis of the risk category.

Management of infectious risk of daratumumab therapy in multiple myeloma: A consensus-based position paper from an ad hoc Italian expert panel.

Daratumumab is approved for newly diagnosed or relapsed/refractory multiple myeloma (MM). The use of daratumumab has improved patient outcomes but has changed the frequency and epidemiology of infections. However, the optimal approach to prophylaxis and supportive therapy for daratumumab-emergent infections is unknown and represents an unmet clinical need in MM.

A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study.

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death.

Pomalidomide, bortezomib, and dexamethasone at first relapse in lenalidomide-pretreated myeloma: A subanalysis of OPTIMISMM by clinical characteristics.

Objective: We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high-risk cytogenetic abnormalities in lenalidomide-pretreated patients with multiple myeloma at first relapse.

Methods: OPTIMISMM was a phase 3, multicenter, open-label, randomized study (NCT01734928; N = 559). The primary endpoint was progression-free survival (PFS).

Daratumumab Monotherapy for Relapsed or Refractory Multiple Myeloma: Results of an Early Access Treatment Protocol in Europe and Russia.

Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38. Despite the demonstrated benefit of daratumumab in multiple myeloma, not all patients have access to commercially available daratumumab. Here we report a pooled analysis of patients from the UK, Spain, Italy, and Russia enrolled in an open-label, early access treatment protocol (EAP) that provided daratumumab (16 mg/kg) monotherapy to patients with heavily pre-treated relapsed or refractory multiple myeloma (RRMM).

Pomalidomide, bortezomib, and dexamethasone for multiple myeloma previously treated with lenalidomide (OPTIMISMM): outcomes by prior treatment at first relapse.

In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone (PVd) demonstrated superior efficacy vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma previously treated with lenalidomide, including those refractory to lenalidomide. This analysis evaluated outcomes in patients at first relapse (N = 226) by lenalidomide-refractory status, prior bortezomib exposure, and prior stem cell transplant (SCT). Second-line PVd significantly improved PFS vs Vd in lenalidomide-refractory (17.

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study.

Background: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19.

Methods: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19.

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses.

Background: Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions.

Methods: Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination).

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse.

Bortezomib- and lenalidomide-containing regimens are well-established therapies in multiple myeloma (MM). However, despite their extensive use, head-to-head comparisons have never been performed. Therefore, we compared bortezomib and lenalidomide in fixed-duration therapies.

Smoldering multiple myeloma: the role of different scoring systems in identifying high-risk patients in real-life practice.

We explore the predictive role of 2014-updated International Myeloma Working Group (IMWG) diagnostic criteria and of some of currently available risk models for progression to symptomatic myeloma when applied in our unselected population of 75 smoldering multiple myeloma (SMM) patients observed between 2000 and 2015. Risk scores including routinely used clinical parameters such as bone marrow plasmacell infiltration rate, immunoparesis, serum monoclonal component (sMC) value, and altered free light chain ratio (FLCr), were clinically useful to identify SMM patients at higher risk of progression. Time to myeloma progression in our ultra-high risk SMM according to IMWG diagnostic update criteria was very short (12.

Management of infectious complications in multiple myeloma patients: Expert panel consensus-based recommendations.

The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunoregulatory drugs and monoclonal antibodies, has improved the outcomes of patients, but in parallel has changed the frequency and epidemiology of infections. Hence, the great strides in the indications and use of new active treatments for MM need parallel progresses on the best approach to prophylaxis and supportive therapy for infections. Moving from the recognition that the above issue represents an unmet clinical need in MM, an expert panel assessed the scientific literature and composed a framework of recommendations for optimal infection control in patients candidate to active treatment for MM.

Non-Secretory Myeloma: Ready for a new Definition?

Non-secretory myeloma is a rare myeloma subtype whose diagnosis, until a few years ago, was established by demonstration of monoclonal plasma cells ≥10% in the bone marrow and by negative results on serum and urine electrophoresis and immunofixation studies. However, this type of myeloma could be misdiagnosed if the workup does not include an accurate study of serum free light chain test since some of the patients diagnosed as non-secretory could be light chain only with small amounts monoclonal proteinuria. Due to this limit in classification, all the information available today, generally coming from retrospective studies including patients studied completely and incompletely, could be misleading.

The amyloidogenic light chain is a stressor that sensitizes plasma cells to proteasome inhibitor toxicity.

Systemic light chain (AL) amyloidosis is caused by the clonal production of an unstable immunoglobulin light chain (LC), which affects organ function systemically. Although pathogenic LCs have been characterized biochemically, little is known about the biology of amyloidogenic plasma cells (PCs). Intrigued by the unique response rates of AL amyloidosis patients to the first-in-class proteasome inhibitor (PI) bortezomib, we purified and investigated patient-derived AL PCs, in comparison with primary multiple myeloma (MM) PCs, the prototypical PI-responsive cells.

Bendamustine, Low-dose dexamethasone, and lenalidomide (BdL) for the treatment of patients with relapsed/refractory multiple myeloma confirms very promising results in a phase I/II study.

Lenalidomide and dexamethasone are an effective treatment for naïve and relapsed multiple myeloma (MM) patients. Bendamustine is a good option for B-cell malignancies showing only partial cross resistance with alkylating agents used in MM patients. Based on these considerations, we proposed a phase I/II study testing escalating doses of bendamustine and lenalidomide and fixed low doses of dexamethasone (BdL).

Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice.

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years.

Implemented myeloma management with whole-body low-dose CT scan: a real life experience.

A total of 318 consecutive myeloma patients underwent whole-body low-dose CT scan (WBLDCT) at baseline and during follow-up as a radiological assessment of lytic lesions in place of skeletal X-ray survey. After WBLDCT baseline assessment, 60% had bone involvement. The presence of lytic lesions represented the only met CRAB (hyperCalcaemia, Renal insufficiency, Anaemia, Bone lesions) criteria in 29% of patients.

Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: A retrospective study.

Objective: Multiple myeloma remains incurable and retreatment with available therapies is of substantial interest.

Methods: This retrospective observational study included data from 35 patients treated initially and at the first relapse with bortezomib-containing regimens.

Results: Bortezomib retreatment provided a similar depth and time to response as first-line therapy; however, as could be expected, the duration of response was shorter with retreatment.