18 results on '"Roschewski, Mark"'
Search Results
2. Phase 1/2 study of acalabrutinib and the PI3K delta inhibitor ACP-319 in relapsed/refractory B-cell Non-Hodgkin lymphoma.
- Author
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Barr PM, Smith SD, Roschewski MJ, O'Brien SM, Sharman JP, Melear JM, Patel P, Calvo R, Yang H, and Spurgeon SE
- Subjects
- Adenosine, Benzamides, Humans, Pyrazines, Quinolines, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell pathology, Phosphatidylinositol 3-Kinases
- Published
- 2022
- Full Text
- View/download PDF
3. CD5-negative mantle cell lymphoma: clinicopathologic features of an indolent variant that confers a survival advantage.
- Author
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Soleimani A, Navarro A, Liu D, Herman SEM, Chuang SS, Slavutsky I, Narbaitz M, Safah H, Schmieg J, Lefante J, Roschewski M, Wilson WH, Wiestner A, and Saba NS
- Subjects
- Adult, Humans, Lymphoma, Mantle-Cell diagnosis, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell therapy
- Abstract
Conventionally, mantle cell lymphoma (MCL) is an aggressive CD5-positive B-cell malignancy with poor prognosis and limited survival. However, a small subset of patients presents with indolent disease and can be managed on a 'watch and wait' approach. CD5-negative MCL has recently been recognized as a more favorable variant of MCL, but its clinical and biological implications remain ill-defined. We performed the most extensive review to-date of all reported cases of CD5-negative MCL and included unpublished cases diagnosed at our institutions to further characterize this disease subset. Based on our analysis of 356 cases of CD5-negative MCL, we conclude that median overall survival exceeds 14 years and is independent of favorable prognostic markers such as leukemic non-nodal disease, absence of SOX11, and low Ki-67.
- Published
- 2022
- Full Text
- View/download PDF
4. A phase 1/2 study of the combination of acalabrutinib and vistusertib in patients with relapsed/refractory B-cell malignancies.
- Author
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Collins GP, Clevenger TN, Burke KA, Yang B, MacDonald A, Cunningham D, Fox CP, Goy A, Gribben J, Nowakowski GS, Roschewski M, Vose JM, Vallurupalli A, Cheung J, Raymond A, Nuttall B, Stetson D, Dougherty BA, Schalkwijk S, Carnevalli LS, Willis B, Tao L, Harrington EA, Hamdy A, Izumi R, Pease JE, Frigault MM, and Flinn I
- Subjects
- B-Lymphocytes, Benzamides, Humans, Morpholines, Pyrazines, Pyrimidines, Neoplasm Recurrence, Local, Protein Kinase Inhibitors therapeutic use
- Abstract
In a phase 1b study of acalabrutinib (a covalent Bruton tyrosine kinase (BTK) inhibitor) in combination with vistusertib (a dual mTORC1/2 inhibitor) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), multiple ascending doses of the combination as intermittent or continuous schedules of vistusertib were evaluated. The overall response rate was 12% (3/25). The pharmacodynamic (PD) profile for acalabrutinib showed that BTK occupancy in all patients was >95%. In contrast, PD analysis for vistusertib showed variable inhibition of phosphorylated 4EBP1 (p4EBP1) without modulation of AKT phosphorylation (pAKT). The pharmacokinetic (PK)/PD relationship of vistusertib was direct for TORC1 inhibition (p4EBP1) but did not correlate with TORC2 inhibition (pAKT). Cell-of-origin subtyping or next-generation sequencing did not identify a subset of DLBCL patients with clinical benefit; however, circulating tumor DNA dynamics correlated with radiographic response. These data suggest that vistusertib does not modulate targets sufficiently to add to the clinical activity of acalabrutinib monotherapy. Clinicaltrials.gov identifier: NCT03205046.
- Published
- 2021
- Full Text
- View/download PDF
5. Hybrid dosing of the cyclin-dependent kinase (CDK) inhibitor flavopiridol in relapsed/refractory mantle cell lymphoma and diffuse large B-cell lymphoma.
- Author
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Miljkovic MD, Roschewski M, Dunleavy K, and Wilson WH
- Subjects
- Adult, Aged, Aged, 80 and over, Cyclin-Dependent Kinases antagonists & inhibitors, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Resistance, Neoplasm, Flavonoids adverse effects, Humans, Infusions, Intravenous methods, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Mantle-Cell pathology, Middle Aged, Neoplasm Recurrence, Local pathology, Piperidines adverse effects, Protein Kinase Inhibitors adverse effects, Treatment Outcome, Young Adult, Flavonoids administration & dosage, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Mantle-Cell drug therapy, Neoplasm Recurrence, Local drug therapy, Piperidines administration & dosage, Protein Kinase Inhibitors administration & dosage
- Published
- 2019
- Full Text
- View/download PDF
6. Phase 1/2 study of alemtuzumab with dose-adjusted EPOCH in untreated aggressive T and NK cell lymphomas.
- Author
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Roswarski J, Roschewski M, Melani C, Pittaluga S, Lucas A, Steinberg SM, Jaffe ES, Waldmann TA, and Wilson WH
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide adverse effects, Cyclophosphamide therapeutic use, Doxorubicin adverse effects, Doxorubicin therapeutic use, Etoposide adverse effects, Etoposide therapeutic use, Female, Humans, Kaplan-Meier Estimate, Lymphoma, Extranodal NK-T-Cell diagnosis, Lymphoma, Extranodal NK-T-Cell mortality, Male, Middle Aged, Neoplasm Staging, Prednisone adverse effects, Prednisone therapeutic use, Treatment Outcome, Vincristine adverse effects, Vincristine therapeutic use, Young Adult, Alemtuzumab administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Extranodal NK-T-Cell drug therapy
- Abstract
To evaluate the feasibility and clinical efficacy of the combination of alemtuzumab with dose-adjusted etoposide/cyclophosphamide/doxorubicin/vincristine/prednisone (DA-EPOCH) as upfront therapy for untreated aggressive T and NK cell lymphomas, a phase 1/2 trial was conducted. Thirty patients were treated with the study regimen, consisting of alemtuzumab on day 1 of a 21 day cycle with standard dosing of DA-EPOCH for 6-8 cycles. Alemtuzumab 30 mg IV was used for the phase 2 component. Of 30 treated patients, 17 had a complete response (CR) and eight had a partial response (83.3% overall response rate). The median overall survival and progression-free survival were 20.2 and 6.6 months, respectively. There were five treatment-related deaths on study mainly due to infectious complications, including one case each of disseminated toxoplasmosis and pneumonia and two cases of sepsis. Alemtuzumab with DA-EPOCH is of limited clinical utility due to unacceptable toxicity, despite the high rate of CR.
- Published
- 2019
- Full Text
- View/download PDF
7. Phase I dose escalation study of the anti-CD2 monoclonal antibody, siplizumab, with DA-EPOCH-R in aggressive peripheral T-cell lymphomas.
- Author
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Roswarski J, Roschewski M, Lucas A, Melani C, Pittaluga S, Jaffe ES, Steinberg SM, Waldmann TA, and Wilson WH
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide adverse effects, Cyclophosphamide therapeutic use, Disease Progression, Doxorubicin adverse effects, Doxorubicin therapeutic use, Etoposide adverse effects, Etoposide therapeutic use, Humans, Kaplan-Meier Estimate, Lymphoma, T-Cell, Peripheral mortality, Lymphoma, T-Cell, Peripheral pathology, Neoplasm Staging, Prednisone adverse effects, Prednisone therapeutic use, Rituximab administration & dosage, Treatment Outcome, Vincristine adverse effects, Vincristine therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, T-Cell, Peripheral drug therapy
- Published
- 2018
- Full Text
- View/download PDF
8. Host-related immunodeficiency in the development of multiple myeloma.
- Author
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Dosani T, Mailankody S, Korde N, Manasanch E, Bhutani M, Tageja N, Roschewski M, Kwok M, Kazandjian D, Costello R, Burton D, Zhang Y, Liewehr D, Steinberg SM, Maric I, and Landgren O
- Subjects
- Aged, Disease Progression, Female, Follow-Up Studies, Humans, Immunologic Deficiency Syndromes immunology, Immunologic Deficiency Syndromes physiopathology, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance pathology, Multiple Myeloma pathology, Paraproteinemias pathology, Prognosis, Prospective Studies, Immunologic Deficiency Syndromes complications, Lymphocytes immunology, Monoclonal Gammopathy of Undetermined Significance etiology, Multiple Myeloma etiology, Paraproteinemias etiology
- Abstract
Host-related immunodeficiency is known to play a role in the development of multiple myeloma (MM) from its precursor conditions (monoclonal gammopathy of undetermined significance, MGUS, smoldering multiple myeloma, SMM). In order to understand the underlying immune changes in this process, we characterized immune patterns from MGUS to SMM to MM. We further sought to identify potential novel immune biomarkers that may predict progression of SMM to MM. We characterized patterns of circulating lymphocytes in 181 patients using multiparametric flow cytometry. We found decreased B- (p = .0003), increased T- (p = .037) and unaltered NK cell proportions from MGUS to SMM to MM. To gain insights into functional variability, we further characterized immunophenotypic lymphocyte subsets, which uncovered differences in CD57 subsets. Specifically, we found that SMM patients who eventually progressed to MM showed decreased proportions of CD57-CD56 + (p = .0061) and CD57-CD16 + (p = .035) lymphocyte subsets. We thus report novel data characterizing the nature of host-related immunodeficiency in the development of MM. We show sequential changes in lymphocyte subsets from MGUS to SMM to MM. We further suggest that CD57 subsets may serve as potential markers of progression from SMM to MM. Our findings support the study of lymphocyte subsets in the search for immune biomarkers. Such markers could provide clinical guidance in managing myeloma precursor disease.
- Published
- 2018
- Full Text
- View/download PDF
9. MYC gene rearrangement in diffuse large B-cell lymphoma does not confer a worse prognosis following dose-adjusted EPOCH-R.
- Author
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Lai C, Roschewski M, Melani C, Pittaluga S, Shovlin M, Steinberg SM, Dunleavy K, Pack S, Jaffe ES, and Wilson WH
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide adverse effects, Cyclophosphamide therapeutic use, Doxorubicin adverse effects, Doxorubicin therapeutic use, Etoposide adverse effects, Etoposide therapeutic use, Humans, Kaplan-Meier Estimate, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse mortality, Prednisone adverse effects, Prednisone therapeutic use, Rituximab administration & dosage, Treatment Outcome, Vincristine adverse effects, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Gene Rearrangement, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Proto-Oncogene Proteins c-myc genetics
- Published
- 2018
- Full Text
- View/download PDF
10. Enzymatic activities of circulating plasma proteasomes in newly diagnosed multiple myeloma patients treated with carfilzomib, lenalidomide and dexamethasone.
- Author
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Manasanch EE, de Larrea CF, Zingone A, Steinberg SM, Kwok M, Tageja N, Bhutani M, Kazandjian D, Roschewski M, Wu P, Carter G, Zuchlinski D, Mulquin M, Lamping L, Costello R, Burton D, Gil LA, Figg WD, Maric I, Calvo KR, Yuan C, Stetler-Stevenson M, Korde N, and Landgren O
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers, Dexamethasone administration & dosage, Enzyme Activation, Female, Humans, Immunoglobulin Isotypes blood, Lenalidomide, Male, Middle Aged, Multiple Myeloma diagnosis, Neoplasm Staging, Neoplasm, Residual diagnosis, Oligopeptides administration & dosage, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma blood, Multiple Myeloma drug therapy, Proteasome Endopeptidase Complex blood
- Abstract
The proteasome inhibitor carfilzomib is highly effective in the treatment of multiple myeloma. It irreversibly binds the chymotrypsin-like active site in the β5 subunit of the 20S proteasome. Despite impressive response rates when carfilzomib is used in combination with immunomodulatory agents in newly diagnosed multiple myeloma patients; no biomarker exists to accurately predict response and clinical outcomes. We prospectively assessed the activity in peripheral blood of the chymotrypsin-like (CHYM), caspase-like (CASP) and trypsin-like (TRYP) proteolytic sites in 45 newly diagnosed multiple myeloma patients treated with eight cycles of carfilzomib, lenalidomide and dexamethasone (CRd) (NCT01402284). Samples were collected per protocol and proteasome activity measured through a fluorogenic assay. Median CHYM levels after one dose of carfilzomib decreased by >70%. CHYM and CASP activity decreased throughout treatment reaching a minimum after eight cycles of treatment. Higher levels of proteasome activity associated with higher disease burden (r > 0.30; p < 0.05) and higher disease stage (0.10 < p <0.20). No association was found with the probability of achieving a complete response, minimal residual disease negativity or time to best response. Further studies evaluating proteasome activity in malignant plasma cells may help elucidate how proteasome activity can be used as a biomarker in multiple myeloma.
- Published
- 2017
- Full Text
- View/download PDF
11. Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging.
- Author
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Bhutani M, Turkbey B, Tan E, Korde N, Kwok M, Manasanch EE, Tageja N, Mailankody S, Roschewski M, Mulquin M, Carpenter A, Lamping E, Minter AR, Weiss BM, Mena E, Lindenberg L, Calvo KR, Maric I, Usmani SZ, Choyke PL, Kurdziel K, and Landgren O
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Female, Fluorodeoxyglucose F18, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance diagnostic imaging, Positron Emission Tomography Computed Tomography, Bone Marrow pathology, Bone and Bones pathology, Multiple Myeloma diagnostic imaging, Precancerous Conditions
- Abstract
The incidence and importance of bone marrow involvement and/or early bone lesions in multiple myeloma (MM) precursor diseases is largely unknown. This study prospectively compared the sensitivity of several imaging modalities in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM. Thirty patients (10 each with MGUS, SMM and MM) were evaluated with skeletal survey, [18F]FDG-PET/CT, [18F]NaF-PET/CT and morphologic dynamic contrast enhanced (DCE)-MRI. An additional 16 SMM patients had skeletal surveys and FDG-PET/CT. Among MGUS patients, DCE-MRI found only one focal marrow abnormality; other evaluations were negative. Among 26 SMM patients, five (19%) were re-classified as MM based on lytic bone lesions on CT and six had unifocal or diffuse marrow abnormality. Among MM, marrow abnormalities were observed on FDG-PET/CT in 8/10 patients and on DCE-MRI in nine evaluable patients. Abnormal NaF uptake was observed only in MM patients with lytic lesions on CT, providing no additional clinical information.
- Published
- 2016
- Full Text
- View/download PDF
12. Secondary diffuse large B-cell lymphoma of the central nervous system: the need for better predictors.
- Author
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Roschewski M and Dunleavy K
- Subjects
- Female, Humans, Male, Central Nervous System Neoplasms pathology, Lymphoma, Large B-Cell, Diffuse therapy
- Published
- 2015
- Full Text
- View/download PDF
13. Flow cytometric sensitivity and characteristics of plasma cells in patients with multiple myeloma or its precursor disease: influence of biopsy site and anticoagulation method.
- Author
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Manasanch EE, Salem DA, Yuan CM, Tageja N, Bhutani M, Kwok M, Kazandjian D, Carter G, Steinberg SM, Zuchlinski D, Mulquin M, Calvo K, Maric I, Roschewski M, Korde N, Braylan R, Landgren O, and Stetler-Stevenson M
- Subjects
- Antigens, Surface metabolism, Biopsy, Bone Marrow pathology, Female, Humans, Immunophenotyping, Male, Plasma Cells metabolism, Flow Cytometry methods, Monoclonal Gammopathy of Undetermined Significance diagnosis, Multiple Myeloma diagnosis, Plasma Cells pathology
- Abstract
Flow cytometry has increasing relevance for prognosis in myeloma and precursor disease (monoclonal gammopathy of unknown significance/smoldering myeloma), yet it has been reported that plasma cell enumeration by flow varies depending on the quality of marrow aspirate and field biopsied in patchy disease. We demonstrated increased sensitivity of flow over immunohistochemistry in abnormal-plasma cell detection in monoclonal gammopathy (n = 59)/smoldering myeloma (n = 87). We prospectively evaluated treatment-na ve smoldering myeloma (n = 9)/myeloma (n = 11) patients for the percentage of abnormal plasma cells/total plasma cell compartment, plasma cell viability/infiltration and flow immunophenotype depending on anticoagulant use, biopsy site and pull sequence in uni-and-bilateral bone marrow biopsies and aspirates. We found no statistical difference regarding the percentage of abnormal plasma cells, their immunophenotype or number/distribution in marrow samples even when obtained by different sequence in aspirates, or anticoagulants (p > 0.05). Our results show that plasma cell enumeration and immunophenotyping by flow cytometry is consistent under different conditions in these populations.
- Published
- 2015
- Full Text
- View/download PDF
14. Moving beyond rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone for diffuse large B-cell lymphoma.
- Author
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Roschewski M, Dunleavy K, and Wilson WH
- Subjects
- Antibodies, Monoclonal, Murine-Derived administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Humans, Molecular Targeted Therapy trends, Prednisone administration & dosage, Rituximab, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Large B-Cell, Diffuse drug therapy, Molecular Targeted Therapy methods
- Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma (NHL). While the de facto treatment standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) is curative in most cases, it is ineffective for a significant proportion of patients, particularly those with intermediate and high-risk disease. Efforts to improve upon the results of R-CHOP have principally explored dose intensification of chemotherapy and resulted in considerable additive toxicity without clear benefit. DLBCL is not a uniform disease, however, and can be dissected into distinct molecular subtypes by gene expression profiling. These subtypes are characterized by distinct oncogenic mechanisms of activation and addictions to aberrant intracellular signaling pathways. Novel therapeutic agents that target these pathway addictions are emerging, and may have specific activity within molecular subtypes of DLBCL. To move beyond R-CHOP for all patients with DLBCL, targeted therapies added to the most effective chemotherapy platforms must be studied within the context of molecularly defined subsets.
- Published
- 2014
- Full Text
- View/download PDF
15. The proteasome: mechanisms of biology and markers of activity and response to treatment in multiple myeloma.
- Author
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Manasanch EE, Korde N, Zingone A, Tageja N, Fernandez de Larrea C, Bhutani M, Wu P, Roschewski M, and Landgren O
- Subjects
- Animals, Antineoplastic Agents therapeutic use, Apoptosis, Biomarkers, Humans, Multiple Myeloma drug therapy, Multiple Myeloma immunology, Plasma Cells immunology, Plasma Cells metabolism, Prognosis, Proteasome Endopeptidase Complex blood, Proteasome Endopeptidase Complex immunology, Proteasome Inhibitors therapeutic use, Treatment Outcome, Multiple Myeloma metabolism, Proteasome Endopeptidase Complex metabolism
- Abstract
Since the early 1990s, the synthesis and subsequent clinical application of small molecule inhibitors of the ubiquitin proteasome pathway (UPP) has revolutionized the treatment and prognosis of multiple myeloma. In this review, we summarize important aspects of the biology of the UPP with a focus on its structure and key upstream/downstream regulatory components. We then review current knowledge of plasma cell sensitivity to proteasome inhibition and highlight new proteasome inhibitors that have recently entered clinical development. Lastly, we address the putative role of circulating proteasomes as a novel biomarker in multiple myeloma and provide guidance for future clinical trials using proteasome inhibitors.
- Published
- 2014
- Full Text
- View/download PDF
16. Lack of MYD88 L265P in non-immunoglobulin M lymphoplasmacytic lymphoma.
- Author
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Manasanch EE, Braylan R, Stetler-Stevenson M, Yuan C, Gounden V, Korde N, Tageja N, Bhutani M, Calvo K, Maric I, Roschewski M, Staudt LM, and Landgren O
- Subjects
- Genetic Heterogeneity, Humans, Amino Acid Substitution, Mutation, Myeloid Differentiation Factor 88 genetics, Waldenstrom Macroglobulinemia genetics
- Published
- 2014
- Full Text
- View/download PDF
17. Modeling progression risk for smoldering multiple myeloma: results from a prospective clinical study.
- Author
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Cherry BM, Korde N, Kwok M, Manasanch EE, Bhutani M, Mulquin M, Zuchlinski D, Yancey MA, Maric I, Calvo KR, Braylan R, Stetler-Stevenson M, Yuan C, Tembhare P, Zingone A, Costello R, Roschewski MJ, and Landgren O
- Subjects
- Disease Progression, Humans, Prognosis, Prospective Studies, Risk, Time Factors, Cell Transformation, Neoplastic, Models, Biological, Monoclonal Gammopathy of Undetermined Significance etiology, Multiple Myeloma etiology
- Abstract
The risk of progression to multiple myeloma (MM) from the precursor condition smoldering MM (SMM) varies considerably among individual patients. Reliable markers for progression to MM are vital to advance the understanding of myeloma precursor disease and for the development of intervention trials designed to delay/prevent MM. The Mayo Clinic and Spanish PETHEMA have proposed models to stratify patient risk based on clinical parameters. The aim of our study was to define the degree of concordance between these two models by comparing the distribution of patients with SMM classified as low, medium and high risk for progression. A total of 77 patients with SMM were enrolled in our prospective natural history study. Per study protocol, each patient was assigned risk scores based on both the Mayo and the Spanish models. The Mayo Clinic model identified 38, 35 and four patients as low, medium and high risk, respectively. The Spanish PETHEMA model classified 17, 22 and 38 patients as low, medium and high risk, respectively. There was significant discordance in overall patient risk classification (28.6% concordance) and in classifying patients as low versus high (p < 0.0001), low versus non-low (p = 0.0007) and high versus non-high (p < 0.0001) risk. There is a need for prospectively validated models to characterize individual patient risk of transformation to MM.
- Published
- 2013
- Full Text
- View/download PDF
18. Evolving therapeutic paradigms for multiple myeloma: back to the future.
- Author
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Cherry BM, Korde N, Kwok M, Roschewski M, and Landgren O
- Subjects
- Combined Modality Therapy methods, Combined Modality Therapy trends, Glucocorticoids administration & dosage, Humans, Interferons administration & dosage, Melphalan administration & dosage, Prednisone administration & dosage, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma therapy, Stem Cell Transplantation methods
- Abstract
Multiple myeloma (MM) is an ancient disease, but until the alkylating agent melphalan was found to have anti-myeloma properties in the 1950s there was virtually no effective therapy. By the late 1960s, extended dosing with melphalan and prednisone tripled survival from diagnosis and became the standard of care for newly diagnosed MM. "Maintenance therapy" to prolong survival through sustained disease control following induction chemotherapy was sought by 1970, but early strategies were ineffective and toxic. Subsequent applications of high-dose therapy (HDT)/autologous stem cell transplant (ASCT) changed the treatment paradigm for MM from extended dosing to an intensive strategy designed to eradicate the malignant cells in a single course of treatment. Although HDT-ASCT resulted in prolonged duration of remission and improved survival, the vast majority of patients still relapsed. Interferon (IFN) and glucocorticoid maintenance therapies demonstrated marginal improvements in outcomes but significant adverse effects. Novel agents introduced over the last decade have prolonged survival when given for maintenance following HDT-ASCT, but have also challenged the HDT-ASCT paradigm by achieving comparable remission rates when used alone as extended frontline therapy. This article reviews the evolution of therapeutic strategies for MM and discusses future questions facing MM investigators.
- Published
- 2013
- Full Text
- View/download PDF
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