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British Journal of Haematology Nov 2016In the last two decades outcomes in multiple myeloma (myeloma) have greatly improved, due to the introduction of newer, more effective therapies. This improvement is not... (Review)
Review
In the last two decades outcomes in multiple myeloma (myeloma) have greatly improved, due to the introduction of newer, more effective therapies. This improvement is not uniform. Response to treatment and survival remains heterogeneous, with some patients living for 1-2 years whilst others are alive and progression-free at 10 years. This variation in outcome is due to patient characteristics plus features intrinsic to the myeloma tumour. Alongside the introduction of novel therapies there has been a greater understanding of disease biology and mechanisms of resistance. This has led to an increase in the number of prognostic markers that can be used in myeloma. This is important not only for more accurate counselling of patients in terms of disease outcome, but also in paving the way for risk-adapted therapy. Both newer and traditional prognostic markers need to be used in the context of planned therapy. Indeed, the prognostic value of certain markers varies according to which therapy the patient receives. As such, these prognostic factors will require constant re-evaluation as agents with new mechanisms of action are added into the myeloma treatment algorithm. This article summarises current concepts of prognostic markers in myeloma.
Topics: Age Factors; Biomarkers; Combined Modality Therapy; Comorbidity; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Multimodal Imaging; Multiple Myeloma; Neoplasm Staging; Phenotype; Prognosis; Transcriptome; Treatment Outcome
PubMed: 27604166
DOI: 10.1111/bjh.14304 -
Blood Cancer Journal Sep 2021
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Disease Management; Humans; Immunotherapy, Adoptive; Lenalidomide; Multiple Myeloma; Stem Cell Transplantation
PubMed: 34535632
DOI: 10.1038/s41408-021-00550-z -
The New England Journal of Medicine May 2018
Topics: Fatal Outcome; Humans; Male; Middle Aged; Multiple Myeloma; Radiography; Skull
PubMed: 29768151
DOI: 10.1056/NEJMicm1714471 -
Blood Cancer Journal May 2023Overall survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional survival (CS) provides dynamic...
Overall survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional survival (CS) provides dynamic survival predictions over time. This study was conducted to estimate CS at 1-8 years from diagnosis and the impact of baseline prognostic factors on CS in multiple myeloma (MM) patients. This is a retrospective study including 2556 MM patients diagnosed between 2004 and 2019. CS (t | s) was defined as the probability of surviving t years given survival of s years. Median age was 64 years. Median follow-up was 6.2 years and median overall survival from diagnosis was 7.5 years. The 5-year CS estimates at s = 0, 1, 2, 3, and 5 years were 0.64, 0.61, 0.61, 0.61, and 0.58, respectively. On multivariate analysis, age ≥ 65 and proteasome inhibitor+immunomodulatory-based induction were associated with decreased survival and increased survival, respectively, retained at 5 years. The adverse impact of 1q gain/amplification, high-risk IgH translocation, and ISS-3 was significant at 1 and 3 years but not 5 years. Chromosome 17 abnormality was associated with decreased survival only at 1 year. Among MM patients, 5-year CS was stable at 1-5 years from diagnosis. The prognostic impact of high-risk cytogenetic factors decreased with additional years survived.
Topics: Humans; Middle Aged; Child, Preschool; Multiple Myeloma; Prognosis; Retrospective Studies; Risk Factors; Chromosome Aberrations
PubMed: 37188699
DOI: 10.1038/s41408-023-00852-4 -
Blood Jan 2023
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 36656612
DOI: 10.1182/blood.2022018157 -
Panminerva Medica Mar 2021Multiple myeloma (MM) represents the second-most common hematologic malignancy. In the 1980s, induction therapy with alkylating agents, such as anthracyclines and... (Review)
Review
Multiple myeloma (MM) represents the second-most common hematologic malignancy. In the 1980s, induction therapy with alkylating agents, such as anthracyclines and steroids, as well as high-dose chemotherapy followed by autologous stem cell transplantation were the main therapeutic approaches for MM. Since the introduction of more effective drugs, such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies and histone deacetylase inhibitor, the new therapeutic algorithm allows of achieving a significantly improvement of prognosis. Numerous regimens, which differently combine these new agents, have been developed and tested in clinical trials. The results of these new regimens are reported each year. In this variegated new contest, old chemotherapeutic drugs still maintain an overriding weight, especially when beneficially combined with new drugs. Also, this is particular true in specific situations, such as extramedullary manifestations, in which tumor mass reduction becomes an urgent clinical need, or in case of chemotherapy-induced stem-cell mobilization. Moreover, melphalan represents the gold standard conditioning regimen since 2002, either alone or, possibly in the next future, in combination with busulfan. Finally, new chemotherapeutic agents with new mechanisms of action, such as melflufen, are in early experimental phase.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Multiple Myeloma; Treatment Outcome
PubMed: 32955186
DOI: 10.23736/S0031-0808.20.04145-2 -
Advances in Experimental Medicine and... 2020It has been speculated for many years that heparanase plays an important role in the progression of cancer due largely to the finding that its expression is weak or... (Review)
Review
It has been speculated for many years that heparanase plays an important role in the progression of cancer due largely to the finding that its expression is weak or absent in normal tissues but generally as tumors become more aggressive heparanase expression increases. However, it is only in the last decade or so that we have begun to understand the molecular mechanism behind the sinister role that heparanase plays in cancer. In this review, we describe the many functions of heparanase in promoting the growth, angiogenesis and metastasis of multiple myeloma, a devastating cancer that localizes predominantly within the bone marrow and spreads throughout the skeletal system devouring bone and ultimately leading to death of almost all patients diagnosed with this disease. We also explore recent discoveries related to how heparanase primes exosome biogenesis and how heparanase enhances myeloma tumor chemoresistance. Discovery of these multiple tumor-promoting pathways that are driven by heparanase identified the enzyme as an ideal target for therapy, an approach recently tested in a Phase I trial in myeloma patients.
Topics: Disease Progression; Drug Resistance, Neoplasm; Exosomes; Glucuronidase; Humans; Multiple Myeloma
PubMed: 32274716
DOI: 10.1007/978-3-030-34521-1_12 -
American Journal of Hematology Jan 2016There have been major advances in the diagnosis, staging, risk-stratification, and management of multiple myeloma (MM). In addition to established CRAB (hypercalcemia,... (Review)
Review
There have been major advances in the diagnosis, staging, risk-stratification, and management of multiple myeloma (MM). In addition to established CRAB (hypercalcemia, renal failure, anemia, and lytic bone lesions) features, new diagnostic criteria include three new biomarkers to diagnose the disease: bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, and >1 focal lesion on magnetic resonance imaging. MM can be classified into several subtypes based on baseline cytogenetics, and prognosis varies according to underlying cytogenetic abnormalities. A Revised International Staging System has been developed which combines markers of tumor burden (albumin, beta-2 microglobulin) with markers of aggressive disease biology (high-risk cytogenetics and elevated serum lactate dehydrogenase). Although the approach to therapy remains largely the same, the treatment options at every stage of the disease have changed. Carfilzomib, pomalidomide, panobinostat, daratumumab, elotuzumab, and ixazomib have been approved for the treatment of the disease. These drugs combined with older agents such as cyclophosphamide, dexamethasone, thalidomide, bortezomib, and lenalidomide dramatically increase the repertoire of regimens available for the treatment of MM. This review provides a concise overview of recent advances in MM, including updates to diagnostic criteria, staging, risk-stratification, and management.
Topics: Antineoplastic Agents; Consolidation Chemotherapy; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Maintenance Chemotherapy; Multiple Myeloma; Neoplasm Staging; Recurrence
PubMed: 26565896
DOI: 10.1002/ajh.24236 -
Biology of Blood and Marrow... Feb 2017
Review
Topics: Aged; Aging; Geriatrics; Humans; Multiple Myeloma
PubMed: 27864162
DOI: 10.1016/j.bbmt.2016.11.007 -
American Journal of Hematology Jul 2016Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma... (Review)
Review
Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. Patients with del(17p), t(14;16), and t(14;20) have high-risk multiple myeloma. Patients with t(4;14) translocation and gain(1q) have intermediate-risk. All others are considered standard-risk. Initial treatment consists of bortezomib, lenalidomide, dexamethasone (VRD). In high-risk patients, carfilzomib, lenalidomide, dexamethasone (KRD) is an alternative to VRD. In eligible patients, initial therapy is given for approximately 3-4 months followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT at first relapse. Patients not candidates for transplant are treated with Rd until progression, or alternatively, a triplet regimen such as VRD for approximately 12-18 months. After ASCT, lenalidomide maintenance is considered for standard risk patients especially in those who are not in very good partial response or better, while maintenance with a bortezomib-based regimen is needed for patients with intermediate or high-risk disease. Patients with indolent relapse can be treated with 2-drug or 3-drug combinations. Patients with more aggressive relapse require a triplet regimen or a combination of multiple active agents. Am. J. Hematol. 91:720-734, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Risk Assessment
PubMed: 27291302
DOI: 10.1002/ajh.24402