Impact of minimal residual disease detection by next-generation flow cytometry in multiple myeloma patients with sustained complete remission after frontline therapy

Minimal residual disease (MRD) was monitored in 52 patients with sustained CR (≥2 years) after frontline therapy using next-generation flow (NGF) cytometry. 25% of patients initially MRD- reversed to MRD+. 56% of patients in sustained CR were MRD+; 45% at the level of 10−5; 17% at 10−6. All patients who relapsed during follow-up were MRD+ at the latest MRD assessment, including those with ultra-low tumor burden. MRD persistence was associated with specific phenotypic profiles: higher erythroblasts’ and tumor-associated monocytes/macrophages’ predominance in the bone marrow niche. NGF emerges as a suitable method for periodic, reproducible, highly-sensitive MRD-detection at the level of 10−6

Clinical implications of chromosomal abnormalities in multiple myeloma

The adverse prognostic role of cytogenetic abnormalities has recently been established in plasma cell dyscrasias. Modern techniques such as fluorescence in situ hybridization and comparative genomic hybridization have revealed a higher incidence of cytogenetic abnormalities in patients with multiple myeloma (MM) compared to conventional cytogenetics. Hypodiploidy and chromosome 13 abnormalities are found in more than 50% of myeloma patients, representing well known factors with adverse prognosis. Rearrangements involving the switch regions of immunoglobulin heavy chain (IgH) gene at 14q32 with various partner genes represent the most common structural abnormalities, having an incidence of 70% in MM. Structural abnormalities of chromosomes 17 and 8 involving the p53 and c-myc genes are considered to be less frequent events, but carry a poor prognosis. New therapeutic approaches such as non-myeloablative allotransplantation and modern therapeutic agents (thalidomide, lenalidomide, and bortezomib) and their combinations give promise for an improved therapeutic management of patients with MM. The detection of t(4; 14), t(14; 16), deletion of chromosome 13 on metaphase analysis, or deletion of p53 by FISH will define high-risk prognostic groups that are not generally controlled with high-dose melphalan and autologous stem cell transplantation (ASCT), and should therefore be treated with more investigational therapies. Alternatively, eligible patients who do not have these poor risk factors are more likely to benefit from a high-dose, melphalan-based, regimen followed by ASCT

Efficacy of panobinostat for the treatment of multiple myeloma

Panobinostat represents a potent oral nonselective pan-histone deacetylase inhibitor (HDAC) with activity in myeloma patients. It has been approved by the FDA and EMA in combination with bortezomib and dexamethasone for the treatment of multiple myeloma, in patients who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. In order to further explore its clinical potential, it is evaluated in different combinations in relapsed/refractory and newly diagnosed multiple myeloma. This review focuses on available data about panobinostat's pharmacology and its role in clinical practice. This review will reveal panobinostat's efficacy as antimyeloma treatment, describing drug evolution from preclinical experimental administration to administration in phase III trials, which established its role in current clinical practice. Based on the latest data, we will present its mechanism of action, its efficacy, and most important issues regarding its toxicity profile. We will further try to shed light on its role in current and future therapeutic landscape of myeloma patients. Panobinostat retains its role in therapy of multiple myeloma because of its manageable toxicity profile and its efficacy, mainly in heavily pretreated multiple myeloma patients. These characteristics make it valuable also for novel regimens in combination with second-generation proteasome inhibitors, IMiDs, and monoclonal antibodies. Results of ongoing trials are expected to shed light on drug introduction in different therapeutic combinations or even at an earlier level of disease course. © 2020 Evangelos Eleutherakis-Papaiakovou et al

Elotuzumab in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma

Introduction: Despite major advances in the therapeutic management of multiple myeloma (MM), it remains an incurable disease. Several combinations of monoclonal antibodies with novel agents are being investigated with promising results in order to prolong progression-free and overall survival. Areas covered: This paper aims to critically present available data from clinical trials investigating the combination of elotuzumab with pomalidomide and dexamethasone in refractory/relapsed MM patients and determine its current role in clinical practice. Expert opinion: Pomalidomide-based combinations with monoclonal antibodies have been shown to be effective in patients with MM who are refractory to or have relapsed following treatment with lenalidomide and/or a proteasome inhibitor (PI). These regimens seem to be more effective than the standard combination of pomalidomide with dexamethasone alone. Taking into consideration that the vast majority of MM patients will receive upfront treatment including a PI and lenalidomide in the near future, pomalidomide-based triplets, such as elotuzumab-pomalidomide-dexamethasone, will become the standard of care in the second line of therapy. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group