Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013

Mıkhael, Joseph; Dingli, David; Roy, Vivek; Reeder, Craig B.; Buadi, Francis K.; Hayman, Suzanne R.; Dispenzieri, Angela; Fonseca, Rafaël; Sher, Taimur; Kyle, Robert A.; Lin, Yi; Russell, Stephen J.; Kumar, Shaji; Bergsagel, P. Leif; Zeldenrust, Steven R.; Leung, Nelson; Drake, Matthew T.; Kapoor, Prashant; Ansell, Stephen M.; Witzig, Thomas E.; Lust, John A.; Dalton, Robert J.; Gertz, Morie A.; Stewart, Keith; Rajkumar, S. Vincent; Chanan‐Khan, Asher; Lacy, Martha Q.

doi:10.1016/j.mayocp.2013.01.019

Cited by 438 publications

(415 citation statements)

References 163 publications

(110 reference statements)

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“…36,37 Amongst the best results reported to date, OS and PFS at 10 years are 62 and 41%, with a long median follow-up of 8.8 years, 13,20,[29][30][31][32][33][34][35] despite sub-optimal induction regimens by today's standards (VAD was administered to 82% of our patients). 38 The main factors explaining these favorable results are very low rates of acute GvHD and NRM. It is well recognized that grades II-IV acute GvHD is associated with deleterious outcome and lower PFS and OS.…”

Section: Discussionmentioning

confidence: 99%

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

Ahmad

LeBlanc

Cohen

et al. 2015

Bone Marrow Transplant

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Despite survival improvement with novel agents and use of autologous hematopoietic stem cell transplantation (HSCT), cure of patients with multiple myeloma (MM) remains anecdotal. Initial observations suggested that chronic GvHD was accompanied by an anti-myeloma effect after myeloablative HSCT, but unfortunately this procedure was hampered by high non-relapse mortality (NRM). To maximize the anti-myeloma effect and minimize NRM, we developed a non-myeloablative (NMA) regimen associated with a high incidence of chronic GvHD and tested its efficacy on patient survival and disease eradication. From 2001 to 2010, 92 patients aged ⩽ 65 years with a compatible sibling donor received autologous HSCT followed by an outpatient NMA allogeneic HSCT using a conditioning of fludarabine and cyclophosphamide. Patient median age was 52 years and 97% presented DurieSalmon stages II-III disease. After a median follow-up of 8.8 years, probability of 10-year progression free and overall survival were 41% and 62%, respectively. Although the cumulative incidence of extensive chronic GvHD was high (at 79%), the majority of longterm survivors were off immunosuppressive drugs by year 5 and NRM was low (at 10%). Together, our results suggest that potential MM cure can be achieved with NMA transplantation regimens that maximize graft-versus-myeloma effect and minimize NRM.

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Section: Discussionmentioning

confidence: 99%

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

Ahmad

LeBlanc

Cohen

et al. 2015

Bone Marrow Transplant

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“…Several groups have worked to develop systems that use prognostic markers to stratify patients with MM into homogeneous survival subgroups 1, 6, 7, 8, 9. Risk stratification facilitates prognostication, allowing patients to be categorized as having lower risk (ie, longer OS) or higher risk (ie, shorter OS) disease.…”

Section: Introductionmentioning

confidence: 99%

Validation of multiple myeloma risk stratification indices in routine clinical practice: Analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies

et al. 2018

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This study used data from the Czech Myeloma Group Registry of Monoclonal Gammopathies to validate the International Myeloma Working Group (IMWG) and revised International Staging System (R‐ISS) indices for risk stratification in patients with multiple myeloma (MM) in clinical practice. Patients were included if they had symptomatic MM, complete data allowing R‐ISS and IMWG staging (including cytogenetic information regarding t(4;14), t(14;16), and del(17p)), and key parameters for treatment evaluation. Median overall survival (OS) in included patients (n = 550) was 47.7 (95% CI: 39.5‐55.9) and 46.2 (95% CI: 38.9‐53.5) months from diagnosis and initiation of first‐line therapy, respectively. Patients categorized as higher vs lower risk had reduced survival; median OS from diagnosis was 35.4 (95% CI: 30.5‐40.3) vs 58.3 (95% CI: 53.8‐62.9) months in high‐risk vs other patients (IMWG; P = .001) and 34.1 (95% CI: 30.2‐38.0) vs 47.2 (95% CI: 43.4‐51.0) months in Stage III vs Stage II patients (R‐ISS; P < .001). In conclusion, IMWG and R‐ISS risk stratification indices are applicable to patients with MM in a real‐world setting.

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“…[4][5][6] Standard pretransplant conditioning consists of 200 mg/m 2 of melphalan (Mel200) based on increased tolerability and efficacy compared with other regimens. 5,6 Most studies evaluating Mel200 excluded patients with RI (42 mg/dL) owing to concerns of increased treatment-related morbidity and non-relapse mortality. There are widely conflicting clinical and pharmacokinetic data in this patient population.…”

Section: Introductionmentioning

confidence: 99%

Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival

Sweiss

Patel

Culos

et al. 2016

Bone Marrow Transplant

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Data on the effectiveness and toxicity of high-dose melphalan in patients with renal impairment (RI) are lacking. We evaluated the impact of RI on outcomes of patients with multiple myeloma treated with melphalan 200 mg/m 2 (Mel200) and autologous stem cell transplantation. Similar baseline characteristics were seen among 46 patients with creatinine clearance (CrCl) o 60 mL/min (median 50 mL/min, range 20-59) and 103 patients with CrCl ⩾ 60 mL/min (median 83 mL/min, range 60-128). Patients with CrCl o60 mL/min had longer time to neutrophil (P = 0.008) and platelet engraftment (P o 0.001). Diarrhea, duration of total parenteral nutrition use and infection were significantly higher in the CrCl o 60 mL/min group. With a median follow-up of 35 months (range 2-132) in the CrCl o60 mL/min group and 47 months (range 1-45) in the CrCl ⩾ 60 mL/min group, overall survival was comparable between the two groups. Median treatment-free survival was longer in the RI group (37 vs 17 months, P = 0.0025). Multivariate analysis showed CrCl o 60 mL/min (hazard ratio (HR) 3.5), and prior proteasome inhibitor therapy (HR 2.441) both predicted longer treatment-free survival. We consider Mel200 safe and effective in patients with CrCl between 30 and 60 mL/min.

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Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013

Cited by 438 publications

References 163 publications

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

Validation of multiple myeloma risk stratification indices in routine clinical practice: Analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies

Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival

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