Multiple Myeloma remains incurable, and there is a need for therapies with novel mechanisms of action. Recently, B cell maturation antigen targeted therapy has demonstrated deep and durable responses in a largely treated population. However, the relapse rate of myeloma patients after anti-BCMA treatment strategies is increasing worldwide, and one of the most challenging issues for them is to choose the best therapy sequencing. After anti-BCMA treatment, retreatment with anti-BCMA drugs remains an option, but new targets are emerging strongly. One of them is G protein-coupled receptor, class C group 5 member D (GPRC5D), that due to the very promising data from the use of chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BsAb) seems to be the ideal candidate in the relay of myeloma treatment at relapse. In this literature review, we discuss data from treatment with the new drugs at relapse after anti-BCMA therapies, observing an undeniable benefit from the use of drugs directed against GPRC5D.

Objective: We investigate safety and efficacy in common clinical practice of the combination of carfilzomib and dexamethasone (Kd56) approved for the ENDEAVOR trial for the treatment of relapsed or refractory multiple myeloma.Methods: We retro‐prospective analyzed 75 patients in three centers in Tuscany, 48 of whom had a clinically relevant comorbidity and 50 of whom were older than 65 years, treated with a median use in the fourth line of therapy. We assessed the efficacy based on the International Myeloma Working Group criteria.Results: The overall response rate was 60%. Median PFS was 10 months in the general cohort; in patients treated for more than 1 cycle of therapy PFS was 12 months. Quality of response to Kd56 treatment was found to positively impact PFS. Refractory status to previous line of therapy or to lenalidomide or an history of exposure to pomalidomide, seemed to have no impact on survival. We also showed a low adverse events rate, with no neuropathy events, and a relatively small number of cardiovascular events above grade 3 (10%).Conclusion: Kd56 is an effective and well tolerated regimen in highly pretreated and elderly patients with a good safety profile.

Systemic amyloidosis arises from monoclonal CD38+ plasma cells that produce misfolded immunoglobulin light chains, which form amyloid fibrils that are deposited into different tissues, leading to organ damage. Daratumumab is a human IgG/k monoclonal antibody that targets CD38, a glycoprotein uniformly expressed on human plasma cells. Daratumumab has been utilized in recent years with unprecedented responses in multiple myeloma. In patients with relapsed or refractory AL amyloidosis, daratumumab has shown promising efficacy in terms of hematologic responses and improvement in organ function. Here, we report real-life treatment with Daratumumab in 33 AL amyloidosis patients treated within the Regional Tuscan Myeloma network at 5 centers with associated MGUS or SMM (n = 15) or symptomatic MM (n = 18). Patients were treated at relapsed/refractory disease stages (n = 29) with a median of one previous line of therapy or at diagnosis (n = 4). Daratumumab showed good efficacy, representing 60% of good hematological responses and 50% of organ responses in a real-life population of patients with an acceptable toxicity profile.

Background and Objectives: The treatment of Myeloma after the second relapse is still challenging. The aim of the study was to investigate the outcomes of the POM-DEX regimen in real clinical practice. Materials and Methods: We retrospectively and prospectively analyzed 121 patients with MM treated with POM-DEX in three Italian sites in Tuscany. We assessed the efficacy based on IMWG Uniform Response Criteria in 106 patients who had received at least two courses of the POM-DEX regimen. The median time from diagnosis to use of POM-DEX was 65 months. POM-DEX median use was in the fourth-line therapy. 63.6% were exposed to lenalidomide or thalidomide, 40.5% to bortezomib or carfilzomib or ixazomib, 5.8% to mAbs in the immediately preceding line of therapy. Results: ORR was 43.4%. Median PFS and OS were 8.5 and 14 months. Eighty-nine patients received more than two courses: their median PFS and OS were 11 and 16 months. When used as the third line of therapy, median PFS and OS were 9 and 20 months and, when patients received POM-DEX for more than two courses, median PFS and OS were 14.5 and 22.5 months. Conclusions: POM-DEX is effective in RRMM, regardless of the latest exposure to IMiDs, PIs, and mAbs in the previous line of therapy.

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.

Background: The management of multiple myeloma is challenging because the disease is incurable and unexpected relapses can threaten a patient's survival. Several assessment systems are currently available, but they often require invasive or costly procedures (e.g., instrumental bone marrow and whole‐body examinations) or rely on non‐specific markers in blood and urine that may not be sufficient to assess and monitor the disease.Aims: To address some of these limitations, the aim of this study was to evaluate the potential use of soluble B‐Cell Maturation Antigen (BCMA), a promising new serum biomarker, as a toll for moniting multiple myeloma patients.Materials & Methods: An unselected cohort of 57 newly diagnosed or relapsed myeloma patients was followed up for 6 months after starting a new therapy. Soluble BCMA levels were measured in peripheral blood using a simple and inexpensive ELISA assay.Results: Soluble BCMA was detectable in peripheral blood by a simple and inexpensive assay in all patients, even in non‐secretory disease or during BCMA‐targeted therapies, and significant changes in its levels were observed over time. The analysis showed that the decrease in sBCMA at 1 and 6 months reflects the quality of the clinical response to anti‐myeloma regimens.Discussion & Conclusion: The data provide interesting insights into the usefulness of sBCMA as a non‐invasive tool for early assessment of treatment efficacy. Its simple and cost‐effective detection in peripheral blood could provide clinicians with an addiotional resource for monitoring disease progression and tailoring treatment strategies.