Definitive results will come from the phase III trial APOLLO (“type”:”clinical-trial”,”attrs”:”text”:”NCT03180736″,”term_id”:”NCT03180736″NCT03180736) comparing Dara-Pd versus Pd in RRMM patients

Definitive results will come from the phase III trial APOLLO (“type”:”clinical-trial”,”attrs”:”text”:”NCT03180736″,”term_id”:”NCT03180736″NCT03180736) comparing Dara-Pd versus Pd in RRMM patients. signs and symptoms, Pixantrone such as hypercalcemia, renal insufficiency, anemia, and lytic bone lesions (CRAB criteria) [3]. The treatment options in MM has changed over the last two decades, and the therapy armamentarium of effective anti-myeloma drugs, used both at diagnosis and at relapse, has expanded significantly with the introduction of several novel agents, including proteasome inhibitors (PIs, bortezomib, carfilzomib, and ixazomib), Pixantrone immunomodulatory drugs (IMiDs, thalidomide, lenalidomide, and pomalidomide), and histone deacetylase blocked (HDAC, panobinostat) [3,4]. With improved treatment regimens and the use of high-dose chemotherapy, followed by autologous hematopoietic stem-cell transplantation (ASCT), median overall survival (OS) of newly diagnosed MM (NDMM) patients eligible for ASCT is 6C8 years. At present, approximately 50% of MM patients are still alive 5 years after the initial diagnosis, even though the OS of these patients, both young and elderly, has steadily risen over the last few years. One-third of the patients can live more than 10 years, according to disease risk staging (International Staging SystemISS) and cytogenetic abnormalities (Revised International Staging SystemR-ISS) that have an impact on prognosis [5]. However, despite the availability of these new drugs and high-dose chemotherapy followed by ASCT, MM still remains largely an incurable disease, even in standard risk patients. Despite most of the patients achieving response with the initial treatment, the majority of them experience a relapse [3]. Natural history of MM is characterized by an alternation of phases of disease remission, followed by phases of relapse. The duration of remission phases tends to progressively decrease at every subsequent relapse, until MM becomes refractory to all available drugs. In newly diagnosed eligible MM patients, a large proportion of patients with MM can now achieve a hematologic complete response (CR), thanks to recent treatment advances that include the combined use of immunomodulatory drugs and proteasome inhibitors, in association with high-dose chemotherapy with ASCT. Unfortunately, despite this, most MM patients achieving CR eventually relapse, suggesting that a very small, but clinically relevant, proportion of clonal plasma cells persist in the bone marrow after therapy, and these cells are not detected by current techniques. Over the last few years, newly specific assays with Pixantrone greater sensitivity have been developed to Rabbit Polyclonal to MMP-3 detect minimal residual disease (MRD), including multiparameter flow cytometry (MFC), allele-specific oligonucleotide quantitative polymerase chain reaction (ASO-qPCR), and next-generation sequencing (NGS) techniques [6]. Currently, the treatment goal of first-line therapy is the achievement of MRD negativity. A large-cohort analysis confirms that MRD status is a value surrogate marker both for progression-free survival (PFS) and OS in patients with MM, including those who had achieved a CR. About 50C80% of transplants-eligible and 15C30% of transplant-ineligible patients achieve MRD negativity after first line treatment based on the new drugs combination. In addition, all recent studies confirmed that MRD has an impact on MM patients outcome, regardless the treatment used [3,6]. In order to prevent and to overcome the natural relapse or treatment resistance, ongoing challenges to identify novel therapeutic strategies and new compounds with different mechanisms of actions are necessary. Over the last few years, scientific attention has been drawn increasingly to immunotherapeutic strategies with the potential for improved targeting for MM clonal plasma cells to maintain a prolonged response, and to achieve a possible cure for MM patients. The field of immune therapy has been accelerating in the treatment of hematological disease and also has a central role in MM. Allogenic stem-cell transplantation (allo-SCT) can be considered the first immunotherapy offering the potential for prolonged survival time in MM patients. T cells of the donor, co-administered with the stem cells, can recognize minor histocompatibility antigen-presenting myeloma cells in.