Osteonecrosis of the Jaw and Bisphosphonates Durie, Brian G M; Katz, Michael; Crowley, John
The New England journal of medicine,
07/2005, Letnik:
353, Številka:
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Journal Article
Recenzirano
Odprti dostop
To the Editor:
Cases of osteonecrosis of the jaw in connection with the use of bisphosphonates were reported in 2003.
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In 2004, the International Myeloma Foundation conducted a Web-based survey ...to assess the risk factors for osteonecrosis of the jaw. Of 1203 respondents, 904 had myeloma and 299 breast cancer. Both osteonecrosis and suspicious findings, including bone erosions and spurs plus exposed bone, were assessed. Sixty-two patients with myeloma had osteonecrosis of the jaw and 54 had suspicious findings; 13 patients with breast cancer had osteonecrosis and 23 had suspicious findings — a total of 152 patients with either . . .
Summary Treatment of multiple myeloma has undergone substantial developments in the past 10 years. The introduction of novel drugs has changed the treatment of the disease and substantially improved ...survival outcomes. Clinical practice guidelines based on evidence have been developed to provide recommendations on standard treatment approaches. However, the guidelines do not take into account resource limitations encountered by developing countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs in Asian countries hinder the delivery of optimum care to every patient with multiple myeloma in Asia. In this Review we outline the guidelines that correspond with different levels of health-care resources and expertise, with the aim to unify diagnostic and therapeutic guidelines and help with the design of future studies in Asia.
The t (11;14) (q13;32) translocation t (11;14) is present in ∼20% of patients with newly diagnosed multiple myeloma (NDMM), but studies examining its prognostic ability have yielded divergent ...results, and data are lacking on outcomes from first-line therapy.
Data from the Connect MM Registry, a large US, multicenter, prospective observational cohort study of patients with NDMM were used to examine the effect of t (11;14) status on first-line therapy outcomes in the Overall population (n = 1574) and race groups (African American AA vs. non-African American NAA).
Baseline characteristics were generally similar between patients with (n = 378) and without (n = 1196) t (11;14). Prevalence of t (11;14) was similar by race (AA, 27%; NAA, 24%). In the overall population, regardless of first-line therapy, t (11;14) status did not affect progression-free survival (hazard ratio, 1.02; P = 0.7675) or overall survival (hazard ratio, 0.99; P = .9417). AA patients with t (11;14) had higher likelihood of death (Nominal Cox regression P = .0298) vs. patients without t (11;14).
Acknowledging observational study and inferential limitations, this exploratory analysis of a predominantly community-based population suggests that t (11;14) is a neutral prognostic factor in the general MM population but may be a negative factor for overall survival in AA patients.
Connect MM Registry is a large, US, multicenter (84% community-based), prospective observational cohort study where the effect of t (11;14) status on first-line therapy outcomes was examined in the newly diagnosed multiple myeloma population. Exploratory analysis results suggest t (11;14) is a neutral prognostic factor in the overall population but may negatively affect overall survival in African American patients.
Whole Body Low Dose CT (WBLDCT) has important advantages as a first-line imaging modality for bone disease assessment in patients with plasma cell disorders and has been included in the 2014 ...International Myeloma Working Group (IMWG) criteria for multiple myeloma (MM) definition. Nevertheless, standardization guidelines for the optimal use of WBLDCT in MM patients are still lacking, preventing its more widespread use, both in daily practice and clinical trials. The aim of this report by the Bone Group of the IMWG is to provide practical recommendations for the acquisition, interpretation and reporting of WBLDCT in patients with multiple myeloma and other plasma cell disorders.
Hemodilution of bone marrow (BM) aspirates is a limitation of multiparameter flow cytometry (MFC) in plasma cell disorders. There is a need for a validated approach for assessing sample quality and ...the distribution of non-plasma cell BM populations by MFC could provide a solution. We evaluated BM-associated cell populations, assessed by next-generation flow cytometry (NGF) and white blood cell (WBC) count in 351 BM aspirated samples from 219 participants with plasma cell disorders in the Iceland Screens, Treats, or Prevents MM study (iStopMM), as markers of hemodilution by their discriminatory ability between first and (generally more hemodiluted) second pull BM aspirated samples. The most discriminating markers were used to derive a novel BM quality index (BMQI). Nucleated red blood cells and myeloid precursors provided the greatest discriminatory ability between first vs second pull samples (area under the curve (AUC): 0.87 and 0.85, respectively), significantly better than B cell precursors (AUC = 0.64; p < 0.001), mast cells (AUC = 0.65; p < 0.001), and the BM WBC count (AUC = 0.77; p < 0.05). We generated a novel BMQI that is intrinsic to current NGF protocols, for evaluating quality of diagnostic BM samples and suggest the use of a BMQI scoring system for interpreting results and guiding appropriate actions.
Proteasome inhibition is an established treatment strategy for patients with multiple myeloma as proteasome inhibitors (PIs) selectively target and disrupt the protein metabolism of aberrant plasma ...cells. Since the introduction of the first-in-class PIs bortezomib, the therapeutic landscape for multiple myeloma has shifted with the development of next-generation PIs (carfilzomib and ixazomib) and new classes of agents. Treatment with modern combination therapies has been shown to result in deep responses and improved outcomes, and these potent regimens are increasingly used as frontline therapy. As patients continue to live longer with modern frontline therapy, there will be an increased need for effective regimens after initial treatment failure. Several recent studies have shown that treatment with combination therapy incorporating PIs induces deep and durable responses in patients with relapsed and/or refractory multiple myeloma. In this review, we review pivotal data and discuss the role of PIs-based doublet and triplet regimens for the management of relapsed/refractory multiple myeloma in the era of modern combination therapy.
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical ...conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.
There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with higher prevalence or increased ...progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore present a target population for MGUS screening. This two-part study is the first study to evaluate the relationship of MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio (OR)= 1.10; 95% confidence interval (CI): 1.00-1.20). This excess risk was limited to prior cancers in the year preceding MGUS screening. A history of prior cancer associated with the progression of MGUS, except for myeloid malignancies which were associated with lower risk of progression (hazard ratio (HR)=0.37; 95%CI: 0.16-0.89; p=0.028). Our findings indicate that a prior cancer are not a significant aetiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a prior cancer.
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