Newly diagnosed multiple myeloma: current treatment strategies, emerging therapeutic approaches and beyond

2020 ◽  
Vol 13 (6) ◽  
pp. 669-686
Author(s):  
Mehmet H Kocoglu ◽  
Ashraf Z Badros
2020 ◽  
Vol 16 (1) ◽  
pp. 5-14 ◽  
Author(s):  
Andrew Branagan ◽  
Matthew Lei ◽  
Uvette Lou ◽  
Noopur Raje

The treatment of multiple myeloma (MM) continues to evolve with the approval of numerous agents over the past decade. Advances in treatment have led to the incorporation of these newer therapies into the treatment paradigm, with improvements in overall survival and the possibility of deep responses including a minimal residual disease–negative state. The strategy of triplet therapies for patients with newly diagnosed MM, followed by high-dose chemotherapy and autologous stem-cell transplantation for eligible patients, and subsequently consolidation and maintenance therapy, is the current treatment roadmap for patients. However, patients with MM will ultimately develop refractoriness to antimyeloma therapies. In this article, we summarize our current practice of managing patients with MM. We highlight our approach to patients with newly diagnosed MM who are transplantation eligible and ineligible and highlight risk-adapted strategies for these patients. In addition, we discuss our approach to the management of patients with relapsed or refractory MM. Last, we review standard therapies and emerging strategies such as targeted approaches, immune-based therapies, and drugs with novel mechanisms of action. Trials evaluating chimeric antigen receptor T cells targeting B-cell maturation antigen are ongoing and are only one of several novel approaches targeting cell maturation antigen, which include the use of bispecific T-cell engager antibodies and antibody drug conjugates. Emerging therapies offer the promise of more individualized approaches in the management of patients with MM and ultimately may result in the possibility of being one step closer to curing patients with MM.


2007 ◽  
Vol 7 ◽  
pp. S139-S144 ◽  
Author(s):  
Sheeba Thomas ◽  
Raymond Alexanian

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3213
Author(s):  
Cirino Botta ◽  
Francesco Mendicino ◽  
Enrica Antonia Martino ◽  
Ernesto Vigna ◽  
Domenica Ronchetti ◽  
...  

Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients.


Author(s):  
Andrew Woodhouse

Human immunodeficiency virus (HIV) infection is a worldwide infection and new cases continue to occur. Recognizing features of acute HIV infection and also underlying conditions that might reflect longer-standing infection are key to diagnosis. This allows treatment to be started which can maintain or improve health and prevent further deterioration of immune function. Treatment is indicated for the majority of newly diagnosed cases irrespective of immune function status. Current treatment strategies are so effective and tolerable now compared to early antiretroviral regimens that HIV has become a long-term manageable condition for the majority of newly diagnosed people who are able to access antiretroviral therapy.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 685-685 ◽  
Author(s):  
Sara Bringhen ◽  
Chiara Cerrato ◽  
Maria Teresa Petrucci ◽  
Mariella Genuardi ◽  
Fabiana Gentilini ◽  
...  

Abstract Background The current treatment for newly diagnosed elderly multiple myeloma (MM) patients, not eligible for transplant, induces approximately 30% near-complete response/complete response (nCR/CR). Carfilzomib is a novel, irreversible proteasome-inhibitor with significant activity and favourable toxicity profile, including very low rates of peripheral neuropathy and neutropenia. We evaluated efficacy and safety of the combination carfilzomib-cyclophosphamide-dexamethasone (CCd) in elderly newly diagnosed MM patients. Methods The Bryant and Day two-stage design was used to evaluate both efficacy and safety. Patients received oral cyclophosphamide (300 mg/m2 on days 1,8,15), oral dexamethasone (40 mg on days 1, 8, 15, 22) and iv carfilzomib administered over 30 minutes (20 mg/m2 on days 1, 2, and 36 mg/m2 on days 8, 9, 15, 16, cycle 1; 36 mg/m2 on days 1, 2, 8, 9, 15, 16, cycles 2-9) every 28 days for 9 cycles, followed by maintenance with iv carfilzomib (36 mg/m2 on days 1, 2, 15, 16) every 28 days until progression or intolerance. Results Enrollment is complete (58 pts): median age was 71 years, 28% of patients were older than 75 years, 40% had ISS stage III, 35% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p] and 31% are frail, defined according to Charlson co-morbidity index (≥2), geriatric assessment score ADL (<4) and IADL (<5) and age with cut-off setting at 80 years. Twenty-five patients completed induction. After 9 induction cycles, 96% of patients achieved at least PR, 76% VGPR, 64% CR/nCR, including 24% stringent-CR. The 1-year PFS was 86% and the 1-year OS was 87%. Grade (G) 4 hematologic AE included neutropenia (3 pts, 5%). G3-4 non-hematologic AEs were infections (4 pts, 7%), cardiac (3 pts, 5%), constitutional (2 pts, 4%), renal (2 pts, 4%) and gastrointestinal complications (1 pt, 2%). Peripheral neuropathy was experienced by 11% of patients and was limited in severity to grade 1 or 2. Overall, the CCd regimen was well tolerated, 20% of patients required dose reduction and only 11% of patients required drug discontinuation during induction due to AEs. Twenty-five patients were assessable for maintenance treatment. After a median duration of maintenance of 6 months, the PR rate was 100%, including 68% CR/nCR (Table). The most frequent toxicity (all grades) during maintenance was fever (G1-2 in 6 pts [24%], G3 in 2 pts [8%]), occurring during the evening following the Carfilzomib infusion and not associated with chills, rigors, dyspnea and/or creatinine increase. There was only 1 (4%) G3 neutropenia and 1 (4%) G2 pericardial effusion. Peripheral neuropathy remained limited (2 pts [8%], all G 1-2). Conclusions The CCd regimen is highly active, showing rapid and deep responses, reaching after 9 cycles, 64% (at least nCR) and 24% sCR, further improving approximately 10-15% during maintenance. These responses compare favorably with the best frontline regimens, showing a doubling in nCR rate. It is well tolerated with limited grade 3-4 AEs, only 11% of patients required drug discontinuation due to AEs. An update will be presented at the meeting. Disclosures: Bringhen: Onyx: Consultancy. Sonneveld:Onyx: Honoraria, Research Funding. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria.


Blood ◽  
2011 ◽  
Vol 118 (17) ◽  
pp. 4519-4529 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Heinz Ludwig ◽  
Meletios A. Dimopoulos ◽  
Joan Bladé ◽  
...  

Abstract Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes.


Blood Reviews ◽  
2019 ◽  
Vol 34 ◽  
pp. 56-66 ◽  
Author(s):  
Dávid Vrábel ◽  
Luděk Pour ◽  
Sabina Ševčíková

2002 ◽  
Vol 13 (2) ◽  
pp. 85-95 ◽  
Author(s):  
Bernard Grosbois ◽  
Olivier Decaux ◽  
Isabelle Azais ◽  
Thierry Facon ◽  
Hervé Avet-Loiseau

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