Outcomes differed markedly between GEP70-defined low-risk and high-risk disease (Figure 4): 5- years PFS rates for low-risk CMM were 41% in TT2–Thal, 59% in TT2+Thal, and 71% in TT3a (P < .0001) (Figure 4A), whereas those for high-risk CMM were 10%, 19%, and 25%, respectively (P = .10) (Figure 4B). In the subset of 627 patients with plasma cell gene expression profiling data, cure plateaus were apparent at 5 years in the 14% with high-risk myeloma compared with 10 years in the remainder with low-risk disease. Results of either method can be complicated by MRI-defined and positron emission tomography–defined focal lesions or macrofocal growth patterns in many CMM patients, which can persist years after onset of clinical CR.

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F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma.

Thus, although increased use of all available therapeutic tools upfront shortened postrelapse survival, the gap between OS and PFS narrowed toward increasing cure fractions. Based on CRD at baseline and a 5-year landmark, TT3a effectuated cure fractions estimated at almost 50% and 75%, respectively, pertaining to the majority of patients with GEP-defined low-risk MM. A relative survival ratio of at least 1 means patient mortality does not exceed that of the general population. Barlogie B, Tricot G, Rasmussen E, Anaissie E, van Rhee F, Zangari M, Fassas A, Hollmig K, Pineda-Roman M, Shaughnessy J, Epstein J, Crowley J. Worldwide: 1-818-487-7455. In the subset of 627 patients with plasma cell gene expression profiling data, cure plateaus were apparent at 5 years in the 14% with high-risk myeloma compared with 10 years in the remainder with low-risk disease. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. We also use analytics & advertising services. (A) Cumulative incidence of CR: GEP-70 low-risk only. We showed persistence of magnetic resonance imaging (MRI)-defined focal lesions in serological and hematological CR,27  extending to the level of MRD negativity defined by multicolor flow cytometry.28  With further follow-up, about 60% of patients qualified for MRI-defined CR (MRI-CR) emerging almost 2 years after onset of clinical CR. The goal? Advances in biology and therapy of multiple myeloma. GEP data of bone marrow biopsies from patients who achieved and remained in CR were compared with those of age- and gender-matched healthy donors. For a disease for which recurrent relapse with new disease has been the "norm," the prospect for cure is a tantalizing opportunity. Bone marrow angiogenesis in myeloma and its precursor disease: a prospective clinical trial. Clipboard, Search History, and several other advanced features are temporarily unavailable.

In the case of TT2, all 258 currently surviving patients of initially 668 have been followed for at least 10 years. The genetic architecture of multiple myeloma. Epub 2013 Nov 22. Of note, despite similar times of onset of CR in TT2+Thal and TT3a, CRD is far superior with TT3a, suggesting that a deeper level of CR was effectuated. A parametric mixture cure model45  was used to estimate PFS and CRD for each protocol, overall and by GEP-70 risk from baseline, as well as from a 5-year landmark for all patients. In the case of myeloma and precursor conditions, myeloma plasma cells coexist in the biopsy material with normal hematopoietic and stromal elements. Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. The Institute’s research nurses and data managers have been critical to the execution of our clinical research efforts. Incorporating new agents with novel mechanisms of action into transplant trials has markedly contributed to improved outcomes14  by achieving high rates of complete remission (CR) as an essential first step toward long-term disease control and cure.15-17  Recent trials with novel agent combinations have achieved high CR rates comparable to those previously reported only with transplants.18  The quality of comparable rates of CR effectuated by different treatment approaches can be judged by their durability after cessation of treatment. The TT approach uses all myeloma-active drugs upfront to target drug-resistant subclones during initial treatment to prevent later relapse. With transition to later protocols, the slopes of time to progression (TTP) (C) and time to relapse (TTR) from CR (D) progressively flatten and reach lower plateaus. (D) OS and PFS: TT3a. Please enable it to take advantage of the complete set of features! Progression estimates by protocol and GEP-70 risk. To identify and treat MGUS at its earliest stage, before it has a chance to develop into full-blown disease. “We can talk about the potential for curing myeloma, because we are so close, and we feel that we are, in fact, already most likely curing patients in the cure trials,” says Dr. Durie. But other factors , such as the tumor’s cytogenetics (chromosome changes), the levels of certain proteins and other substances in the blood, your kidney function, your age and overall health, can also affect your outlook. (B) CRD by protocol. High CR rates comparable to those achieved with more toxic autotransplant-supported high-dose melphalan have recently been reported with the sole use of novel-agent combinations. Our data show that for patients with high-risk CMM, novel therapies are needed. Tumor microenvironment and drug resistance in hematologic malignancies. Eight-year median survival in multiple myeloma after total therapy 2: roles of thalidomide and consolidation chemotherapy in the context of total therapy 1. Complete response in myeloma: a Trojan horse? Components of Total Therapy trials TT1, TT2, and TT3a. The baseline characteristics of patients accrued to TT trials are similar across studies (supplemental Table 1, see supplemental Data available at the Blood Web site). Here, we address the curability of myeloma from the vantage point of having followed all patients treated in the Arkansas program for life. The use of mixture models for the analysis of survival data with long-term survivors. COVID-19 is an emerging, rapidly evolving situation. One of the major impediments to curing MM is ITH. Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. A subset of 627 patients enrolled in TT2 and TT3a trials had available gene expression profiling (GEP) data. Essential Tests for Diagnosis and Monitoring.

By exerting stimulatory effects also on MM cells, such cytokine release may contribute to MM survival and disease escape.

Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease. Get the latest research from NIH: https://www.nih.gov/coronavirus. Complete remission in multiple myeloma examined as time-dependent variable in terms of both onset and duration in Total Therapy protocols. A minority of patients had discordant readings between CR and MRD designations, 4 CRs were MRD-positive and 3 MRD-negative patients did not fulfill clinical CR criteria.