Author
C. S. Chim
Bio: C. S. Chim is an academic researcher from Queen Mary University of London. The author has contributed to research in topics: Multiple myeloma & Transplantation. The author has an hindex of 9, co-authored 11 publications receiving 991 citations.
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National University of Singapore1, Mayo Clinic2, Queen Mary University of London3, Heidelberg University4, Columbia University5, Harvard University6, University of Turin7, Spanish National Research Council8, Erasmus University Medical Center9, University of Bologna10, University of Arkansas for Medical Sciences11, Cedars-Sinai Medical Center12
TL;DR: The International Myeloma Working Group proposes well-defined and easily applicable risk categories based on current available information and suggests the use of this set of prognostic factors as gold standards in all clinical trials and form the basis of subsequent development of more complex prognostic system or better prognostic Factors.
Abstract: Multiple myeloma is characterized by underlying clinical and biological heterogeneity, which translates to variable response to treatment and outcome. With the recent increase in treatment armamentarium and the projected further increase in approved therapeutic agents in the coming years, the issue of having some mechanism to dissect this heterogeneity and rationally apply treatment is coming to the fore. A number of robustly validated prognostic markers have been identified and the use of these markers in stratifying patients into different risk groups has been proposed. In this consensus statement, the International Myeloma Working Group propose well-defined and easily applicable risk categories based on current available information and suggests the use of this set of prognostic factors as gold standards in all clinical trials and form the basis of subsequent development of more complex prognostic system or better prognostic factors. At the same time, these risk categories serve as a framework to rationalize the use of therapies.
489 citations
University of Salamanca1, Harvard University2, Mayo Clinic3, University of Turin4, University of Texas MD Anderson Cancer Center5, University of Arkansas for Medical Sciences6, Carolinas Healthcare System7, Indiana University – Purdue University Indianapolis8, Cornell University9, University of Würzburg10, National and Kapodistrian University of Athens11, University of Toulouse12, University of Gothenburg13, Lund University14, Vrije Universiteit Brussel15, Roswell Park Cancer Institute16, Queen Mary University of London17, University of New Brunswick18, VU University Medical Center19, Tufts University20, National University of Singapore21, Erasmus University Rotterdam22
TL;DR: This work reviews the biological rationale for the use of the most important new agents for treating Multiple myeloma, and discusses data from already approved and active agents (including second- and third-generation proteasome inhibitors, immunomodulatory agents and alkylators).
Abstract: Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting.
210 citations
Harvard University1, University of California, San Francisco2, Karolinska University Hospital3, Memorial Hospital of South Bend4, University of North Carolina at Chapel Hill5, Aalborg University6, University of Cambridge7, Jagiellonian University Medical College8, Sahlgrenska University Hospital9, National University of Singapore10, Cross Cancer Institute11, Second Military Medical University12, University of Bologna13, Queen Mary University of London14, New York University15, Peking University16, Saint John Regional Hospital17, Royal Prince Alfred Hospital18, Dublin City University19, National and Kapodistrian University of Athens20, Roswell Park Cancer Institute21, University of Texas MD Anderson Cancer Center22, University of Navarra23, University of Turin24, Mayo Clinic25, Cedars-Sinai Medical Center26
TL;DR: This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics.
Abstract: The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.
189 citations
TL;DR: Multivariate analysis involving presentation features, international prognostic index (IPI), Korean prognostic score and EBV DNA parameters showed that negative EBVDNA after SMILE (I) had the most significant impact on overall survival and pattern AEBV DNA change had the largest impact on disease-free survival.
Abstract: Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its significance in natural killer/T-cell lymphoma treated with the novel regimen SMILE was investigated. EBV DNA was quantified with a World Health Organization EBV standard in 910 plasma samples collected during 230 courses of SMILE in 56 patients. Median presentation EBV DNA was 1900 (0-1.4 × 10(7)) IU/ml. Presentation EBV DNA was significantly associated with tumor load and treatment response. To examine lymphoma chemosensitivity, EBV DNA changes after SMILE were evaluated. EBV DNA after SMILE (I) significantly correlated with tumor load and treatment response. Two dynamic parameters were further analyzed: negative EBV DNA after SMILE (I) and EBV DNA change patterns during treatment (A: persistently undetectable; B: persistently detectable presentation). Negative EBV DNA after SMILE (I) and pattern A EBV DNA change significantly correlated with lower tumor load and superior outcome. Multivariate analysis involving presentation features, international prognostic index (IPI), Korean prognostic score and EBV DNA parameters showed that negative EBV DNA after SMILE (I) had the most significant impact (P<0.001) on overall survival and pattern A EBV DNA change had the most significant impact (P=0.002) on disease-free survival. Presentation EBV DNA, IPI and Korean prognostic scores were not independent prognostic factors.
107 citations
TL;DR: An unusual patient in whom lymphoma occurred initially as isolated lymph node involvement, an exceptional presentation of an almost exclusively extranodal disease is described.
Abstract: Natural killer (NK) cell lymphomas are rare, and atypical features might lead to diagnostic pitfalls. This report describes an unusual patient in whom lymphoma occurred initially as isolated lymph node involvement, an exceptional presentation of an almost exclusively extranodal disease. Furthermore, during the terminal haemophagocytosis in the bone marrow, lymphoma cells lost the expression of the NK cell marker, CD56, making the histopathological diagnosis of bone marrow involvement difficult. This was resolved by in situ hybridisation for Epstein-Barr virus encoded small RNA, which detected occult bone marrow infiltration.
37 citations
Cited by
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Mayo Clinic1, University of Navarra2, Harvard University3, Cedars-Sinai Medical Center4, Memorial Sloan Kettering Cancer Center5, Emory University6, National and Kapodistrian University of Athens7, University of Turin8, Mount Sinai Hospital9, University of Texas MD Anderson Cancer Center10, Heidelberg University11, Alfred Hospital12, University Health System13, Carolinas Healthcare System14, University of Bologna15, Aalborg University16, Dalhousie University17, Erasmus University Rotterdam18, Roswell Park Cancer Institute19, Columbia University20, University of Toulouse21
TL;DR: Several aspects of disease response assessment are clarified, along with endpoints for clinical trials, and future directions for disease response assessments are highlighted, to allow uniform reporting within and outside clinical trials.
Abstract: Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.
1,681 citations
TL;DR: The addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited.
Abstract: BackgroundIxazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma. MethodsIn this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma to receive ixazomib plus lenalidomide–dexamethasone (ixazomib group) or placebo plus lenalidomide–dexamethasone (placebo group). The primary end point was progression-free survival. ResultsProgression-free survival was significantly longer in the ixazomib group than in the placebo group at a median follow-up of 14.7 months (median progression-free survival, 20.6 months vs. 14.7 months; hazard ratio for disease progression or death in the ixazomib group, 0.74; P=0.01); a benefit with respect to progression-free survival was observed with the ixazomib regimen, as compared with the placebo regimen, in all prespecified patient subgroups, including in patients with high-risk cytogenetic abnormalities. The overall rates of...
821 citations
Emory University1, University of Pennsylvania2, Carolinas Healthcare System3, Northwestern University4, Icahn School of Medicine at Mount Sinai5, University of Calgary6, Cross Cancer Institute7, City of Hope National Medical Center8, Cedars-Sinai Medical Center9, University of Salamanca10, New York University11, University of Texas MD Anderson Cancer Center12, University of British Columbia13, Oregon Health & Science University14, Sarah Cannon Research Institute15, Rutgers University16, Hôpital Maisonneuve-Rosemont17, University of Wisconsin-Madison18, University of Chicago19, Dalhousie University20, Harvard University21, Genmab22, Janssen Pharmaceutica23, University of North Carolina at Chapel Hill24
TL;DR: Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma, with a favourable safety profile in this population of patients.
680 citations
TL;DR: These Clinical Practice Guidelines are endorsed by the Japanese Society of Medical Oncology (JSMO) incidence and epidemiology Multiple myeloma accounts for 1% ofall cancers and ∼10% of all haematological malignancies.
658 citations
Erasmus University Rotterdam1, Emory University2, Carolinas Healthcare System3, Hackensack University Medical Center4, Harvard University5, Mayo Clinic6, Heidelberg University7, University of Navarra8, University of Barcelona9, University Hospital Heidelberg10, University of Turin11, University of Texas MD Anderson Cancer Center12
TL;DR: Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p), whereas lenalidomide may be associated with improved progression-based survival and progression- free survival int( 4;14), del( 17/17 p), and t(14;16), and gain(1q).
620 citations