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| Name | Class |
|---|---|
| Sun Yat-Sen University Cancer Center | OTHER |
| Ruijin Hospital | OTHER |
| Second Hospital of Shanxi Medical University | OTHER |
| The First Affiliated Hospital of Air Force Medicial University |
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Frailty is dynamic and confers poor outcomes in elderly patients with newly diagnosed multiple myeloma (NDMM), mainly because of the high prevalence of treatment discontinuation due to intolerability. We designed a multi-center prospective study (DynaFiT) based on our real-life practice to evaluate the feasibility and benefits of a dynamic frailty-tailored therapy in elderly patients with different fitness/frailty statuses.
Since Dara-based treatment have recently become the new standard regimens, in this amendment of the study, daratumumab added to VRd is recommended as induction therapy regimen.
Older patients with MM represent a heterogeneous population with different fitness/frailty statuses. Unlike fit patients who can benefit from intensive therapies due to their endurance, frail patients are often susceptible to treatment-related toxicity, leading to treatment discontinuation and poor outcomes. More importantly, frailty can diminish the prognostic impact of disease-related factors over disease trajectory. Thus, it is of utmost importance to determine the fitness/frailty status for treatment decision-making that carefully balances efficacy and safety in this vulnerable population. However, geriatric assessment is often conducted at diagnosis in clinical practice. Although baseline frailty status, as a static risk factor, is significantly associated with OS, its predictive ability decreases over time. Of note, emerging evidence indicates that the fitness/frailty status is highly dynamic because of age increase, disease trajectory, and treatment, raising the notion that frailty-tailored therapy should be designed based on the baseline fitness/frailty status and also according to its longitudinal changes during the treatment course. Thus, current frailty status better predicts OS.
To improve outcomes in elderly patients, this study was designed to investigate an entirely novel therapeutic strategy, the dynamic frailty-tailored therapy, in elderly MM patients with different fitness/frailty statuses.
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| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (at least PR) on induction therapy | Overall response rate(ORR) is defined as the percentage of participants with presence of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). ORR assessment will be based on International Myeloma Working Group (IMWG) response criteria. | From the date of inclusion to the end of induction therapy, up to 8 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of treatment discontinued(TD) | The effect of intensive or mild treatment based on dynamic frailty status on treatment discontinued(TD) in elderly newly diagnosed multiple myeloma. | The time from the date of inclusion to the date of treatment discontinued from any cause, up to 24 months. |
| Treatment related adverse event(TRAE) |
| Measure | Description | Time Frame |
|---|---|---|
| To establish a new and better comprehensive geriatric assessment system to predict prognosis of elderly NDMM | To establish a new and better comprehensive geriatric frailty assessment system that can predict TD and OS in NDMM patients, combining objective biological markers (biomarkers of sarcopenia, n-terminal pro-brain natriuretic peptide, inflammatory markers such as C-reactive protein, aging biomarkers, and immune markers). |
Inclusion Criteria:
Monoclonal plasma cells in the bone marrow 10% or presence of a biopsy-proven plasmacytoma;
Measurable disease as defined by any of the following:
Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
IgA multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
Light chain multiple myeloma: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
Exclusion Criteria:
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Diagnosed with primary multiple myeloma according to the 2014 IMWG multiple myeloma diagnostic criteria,aged ≥65 years who were either transplant-ineligible or had no intent for immediate transplant.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Hospital of Jilin University | Recruiting | Changchun | Jilin | 130021 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28726797 | Background | Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, Gay F, Anderson KC. Multiple myeloma. Nat Rev Dis Primers. 2017 Jul 20;3:17046. doi: 10.1038/nrdp.2017.46. | |
| 31560378 | Background | Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, Abdel-Rahman O, Abdelalim A, Abdoli A, Abdollahpour I, Abdulle ASM, Abebe ND, Abraha HN, Abu-Raddad LJ, Abualhasan A, Adedeji IA, Advani SM, Afarideh M, Afshari M, Aghaali M, Agius D, Agrawal S, Ahmadi A, Ahmadian E, Ahmadpour E, Ahmed MB, Akbari ME, Akinyemiju T, Al-Aly Z, AlAbdulKader AM, Alahdab F, Alam T, Alamene GM, Alemnew BTT, Alene KA, Alinia C, Alipour V, Aljunid SM, Bakeshei FA, Almadi MAH, Almasi-Hashiani A, Alsharif U, Alsowaidi S, Alvis-Guzman N, Amini E, Amini S, Amoako YA, Anbari Z, Anber NH, Andrei CL, Anjomshoa M, Ansari F, Ansariadi A, Appiah SCY, Arab-Zozani M, Arabloo J, Arefi Z, Aremu O, Areri HA, Artaman A, Asayesh H, Asfaw ET, Ashagre AF, Assadi R, Ataeinia B, Atalay HT, Ataro Z, Atique S, Ausloos M, Avila-Burgos L, Avokpaho EFGA, Awasthi A, Awoke N, Ayala Quintanilla BP, Ayanore MA, Ayele HT, Babaee E, Bacha U, Badawi A, 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Drake TM, Dubey M, Dubljanin E, Duken EE, Ebrahimi H, Effiong A, Eftekhari A, El Sayed I, Zaki MES, El-Jaafary SI, El-Khatib Z, Elemineh DA, Elkout H, Ellenbogen RG, Elsharkawy A, Emamian MH, Endalew DA, Endries AY, Eshrati B, Fadhil I, Fallah Omrani V, Faramarzi M, Farhangi MA, Farioli A, Farzadfar F, Fentahun N, Fernandes E, Feyissa GT, Filip I, Fischer F, Fisher JL, Force LM, Foroutan M, Freitas M, Fukumoto T, Futran ND, Gallus S, Gankpe FG, Gayesa RT, Gebrehiwot TT, Gebremeskel GG, Gedefaw GA, Gelaw BK, Geta B, Getachew S, Gezae KE, Ghafourifard M, Ghajar A, Ghashghaee A, Gholamian A, Gill PS, Ginindza TTG, Girmay A, Gizaw M, Gomez RS, Gopalani SV, Gorini G, Goulart BNG, Grada A, Ribeiro Guerra M, Guimaraes ALS, Gupta PC, Gupta R, Hadkhale K, Haj-Mirzaian A, Haj-Mirzaian A, Hamadeh RR, Hamidi S, Hanfore LK, Haro JM, Hasankhani M, Hasanzadeh A, Hassen HY, Hay RJ, Hay SI, Henok A, Henry NJ, Herteliu C, Hidru HD, Hoang CL, Hole MK, Hoogar P, Horita N, Hosgood HD, Hosseini M, 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HMA, Majeed A, Maleki A, Malekzadeh R, Manafi A, Manafi N, Manamo WA, Mansourian M, Mansournia MA, Mantovani LG, Maroufizadeh S, Martini SMS, Mashamba-Thompson TP, Massenburg BB, Maswabi MT, Mathur MR, McAlinden C, McKee M, Meheretu HAA, Mehrotra R, Mehta V, Meier T, Melaku YA, Meles GG, Meles HG, Melese A, Melku M, Memiah PTN, Mendoza W, Menezes RG, Merat S, Meretoja TJ, Mestrovic T, Miazgowski B, Miazgowski T, Mihretie KMM, Miller TR, Mills EJ, Mir SM, Mirzaei H, Mirzaei HR, Mishra R, Moazen B, Mohammad DK, Mohammad KA, Mohammad Y, Darwesh AM, Mohammadbeigi A, Mohammadi H, Mohammadi M, Mohammadian M, Mohammadian-Hafshejani A, Mohammadoo-Khorasani M, Mohammadpourhodki R, Mohammed AS, Mohammed JA, Mohammed S, Mohebi F, Mokdad AH, Monasta L, Moodley Y, Moosazadeh M, Moossavi M, Moradi G, Moradi-Joo M, Moradi-Lakeh M, Moradpour F, Morawska L, Morgado-da-Costa J, Morisaki N, Morrison SD, Mosapour A, Mousavi SM, Muche AA, Muhammed OSS, Musa J, Nabhan AF, Naderi M, Nagarajan AJ, Nagel G, 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Salem MR, Salimzadeh H, Salomon JA, Samy AM, Sanabria J, Santric Milicevic MM, Sartorius B, Sarveazad A, Sathian B, Satpathy M, Savic M, Sawhney M, Sayyah M, Schneider IJC, Schottker B, Sekerija M, Sepanlou SG, Sepehrimanesh M, Seyedmousavi S, Shaahmadi F, Shabaninejad H, Shahbaz M, Shaikh MA, Shamshirian A, Shamsizadeh M, Sharafi H, Sharafi Z, Sharif M, Sharifi A, Sharifi H, Sharma R, Sheikh A, Shirkoohi R, Shukla SR, Si S, Siabani S, Silva DAS, Silveira DGA, Singh A, Singh JA, Sisay S, Sitas F, Sobngwi E, Soofi M, Soriano JB, Stathopoulou V, Sufiyan MB, Tabares-Seisdedos R, Tabuchi T, Takahashi K, Tamtaji OR, Tarawneh MR, Tassew SG, Taymoori P, Tehrani-Banihashemi A, Temsah MH, Temsah O, Tesfay BE, Tesfay FH, Teshale MY, Tessema GA, Thapa S, Tlaye KG, Topor-Madry R, Tovani-Palone MR, Traini E, Tran BX, Tran KB, Tsadik AG, Ullah I, Uthman OA, Vacante M, Vaezi M, Varona Perez P, Veisani Y, Vidale S, Violante FS, Vlassov V, Vollset SE, Vos T, Vosoughi K, Vu GT, Vujcic IS, Wabinga H, Wachamo TM, Wagnew FS, Waheed Y, Weldegebreal F, Weldesamuel GT, Wijeratne T, Wondafrash DZ, Wonde TE, Wondmieneh AB, Workie HM, Yadav R, Yadegar A, Yadollahpour A, Yaseri M, Yazdi-Feyzabadi V, Yeshaneh A, Yimam MA, Yimer EM, Yisma E, Yonemoto N, Younis MZ, Yousefi B, Yousefifard M, Yu C, Zabeh E, Zadnik V, Moghadam TZ, Zaidi Z, Zamani M, Zandian H, Zangeneh A, Zaki L, Zendehdel K, Zenebe ZM, Zewale TA, Ziapour A, Zodpey S, Murray CJL. 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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D000073496 | Frailty |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| OTHER |
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Blood, Bone marrow
Toxicity and safety will be reported based on the adverse events, as graded by CTCAE V5 and determined by routine clinical assessments. |
| Baseline, end of every induction cycle and maintenance cycle, until disease progression or treatment discontinued, up to 24 months. |
| Early mortality(EM) | Early mortality is defined as death within 3, 6, 12 and 24 months (EM3,EM6,EM12 and EM24). | The time from the date of inclusion to the date of death from any cause, up to 24 months. |
| Progression-free survival(PFS) | Progression-free survival(PFS) is defined as the time from inclusion to the time of first documented evidence of disease progression or death from any cause. Individuals who are lost to follow-up or progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. Disease progression is defined according to the IMWG Uniform Response Criteria for Multiple Myeloma. | The time from the date of inclusion to the date of first documented evidence of disease progression or death from any cause, up to 24 months. |
| Overall survival (OS) | In each case it is the time from inclusion to the time of death from any cause. Individuals who are lost to follow-up or still alive at the time of analysis will be censored at their last known date to be alive. | The time from the date of inclusion to the date of death from any cause, up to 24 months |
| Through study completion, up to 24 months. |
| To explore the value of sarcopenia in predicting treatment discontinued(TD) and prognosis of the elderly newly diagnosed multiple myeloma | Number of participants with imaging sarcopenia as assessed by dual-energy X-ray absorptiometry and whole-body low-dose CT;Number of participants with functional sarcopenia as assessed by grip strength and 6-meter walking speed;Number of participants with objective biomarkers in sarcopenia as assessed by peripheral blood test. | Through study completion, up to 24 months. |
| Minimal residual disease (MRD) | By using multiparameter flow cytometry and/or next-generation sequencing techniques dynamically monitor MRD status and its effect on OS and PFS | Through study completion, up to 24 months. |
| Discovery and identification of frailty biomarkers in elderly newly diagnosed multiple myeloma | Discovery and identification of frailty biomarkers in elderly newly diagnosed multiple myeloma. | Through study completion, up to 24 months. |
| To explore the prognostic significance of blood liquid biopsy based on platelet RNA sequencing for multiple myeloma | Heterogeneity of disease as assessed by platelet RNA sequencing to explore the prognostic significance of blood liquid biopsy based on for multiple myeloma. | Through study completion, up to 24 months. |
| To establish a predictive model for treatment discontinuation in elderly NDMM. | To identify elderly NDMM who are intolerant to standard-dose therapy, a predictive model for treatment discontinuation will be constructed. Proactive management will be implemented for patients at high risk of treatment discontinuation, including appropriate reduction of treatment intensity and active supportive care. | The time from the date of inclusion to the date of treatment discontinued, up to 24 months |
| 24157580 | Background | Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, Kapoor P, Dingli D, Hayman SR, Leung N, Lust J, McCurdy A, Russell SJ, Zeldenrust SR, Kyle RA, Rajkumar SV. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014 May;28(5):1122-8. doi: 10.1038/leu.2013.313. Epub 2013 Oct 25. |
| 30071357 | Background | Cardoso AL, Fernandes A, Aguilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA, Ortolano S, Pani G, Athanasopoulou S, Gonos ES, Schosserer M, Grillari J, Peterson P, Tuna BG, Dogan S, Meyer A, van Os R, Trendelenburg AU. Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res Rev. 2018 Nov;47:214-277. doi: 10.1016/j.arr.2018.07.004. Epub 2018 Jul 30. |
| 23445873 | Background | Bringhen S, Mateos MV, Zweegman S, Larocca A, Falcone AP, Oriol A, Rossi D, Cavalli M, Wijermans P, Ria R, Offidani M, Lahuerta JJ, Liberati AM, Mina R, Callea V, Schaafsma M, Cerrato C, Marasca R, Franceschini L, Evangelista A, Teruel AI, van der Holt B, Montefusco V, Ciccone G, Boccadoro M, San Miguel J, Sonneveld P, Palumbo A. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica. 2013 Jun;98(6):980-7. doi: 10.3324/haematol.2012.075051. Epub 2013 Feb 26. |
| 26240224 | Background | Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015 Sep 10;33(26):2863-9. doi: 10.1200/JCO.2015.61.2267. Epub 2015 Aug 3. |
| 25628469 | Background | Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27. |
| 35654466 | Background | Coulson AB, Royle KL, Pawlyn C, Cairns DA, Hockaday A, Bird J, Bowcock S, Kaiser M, de Tute R, Rabin N, Boyd K, Jones J, Parrish C, Gardner H, Meads D, Dawkins B, Olivier C, Henderson R, Best P, Owen R, Jenner M, Kishore B, Drayson M, Jackson G, Cook G. Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial. BMJ Open. 2022 Jun 2;12(6):e056147. doi: 10.1136/bmjopen-2021-056147. |
| 34673897 | Background | Yao Y, Sui WW, Liao AJ, Wang W, Chen LJ, Chu XX, Bao L, Cen XN, Fu R, Liu H, Sun CY, Jin FY, Yan H, Wang LQ, Yuan CL, Gao GX, Gao D, Zhang JQ, He JX, Hu JD, Ma LM, Zhang L, Zhou DB, Zou DH, Li J. Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study. Age Ageing. 2022 Jan 6;51(1):afab211. doi: 10.1093/ageing/afab211. |
| 29880892 | Background | Larocca A, Dold SM, Zweegman S, Terpos E, Wasch R, D'Agostino M, Scheubeck S, Goldschmidt H, Gay F, Cavo M, Ludwig H, Straka C, Bringhen S, Auner HW, Caers J, Gramatzki M, Offidani M, Dimopoulos MA, Einsele H, Boccadoro M, Sonneveld P, Engelhardt M. Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN). Leukemia. 2018 Aug;32(8):1697-1712. doi: 10.1038/s41375-018-0142-9. Epub 2018 Apr 25. |
| 33945289 | Background | Stege CAM, Nasserinejad K, van der Spek E, Bilgin YM, Kentos A, Sohne M, van Kampen RJW, Ludwig I, Thielen N, Durdu-Rayman N, de Graauw NCHP, van de Donk NWCJ, de Waal EGM, Vekemans MC, Timmers GJ, van der Klift M, Soechit S, Geerts PAF, Silbermann MH, Oosterveld M, Nijhof IS, Sonneveld P, Klein SK, Levin MD, Zweegman S. Ixazomib, Daratumumab, and Low-Dose Dexamethasone in Frail Patients With Newly Diagnosed Multiple Myeloma: The Hovon 143 Study. J Clin Oncol. 2021 Sep 1;39(25):2758-2767. doi: 10.1200/JCO.20.03143. Epub 2021 May 4. |
| 33589752 | Background | Stege CAM, Nasserinejad K, Klein SK, Timmers GJ, Hoogendoorn M, Ypma PF, Nijhof IS, Velders GA, Strobbe L, Durdu-Rayman N, Westerman M, Davidis-van Schoonhoven MA, van Kampen RJW, Beeker A, Koster A, Dijk AC, van de Donk NWCJ, van der Spek E, Leys RBL, Silbermann MH, Groen K, van der Burg-de Graauw NCHP, Sinnige HAM, van der Hem KG, Levenga H, Bilgin YM, Sonneveld P, Levin MD, Zweegman S. Improving the identification of frail elderly newly diagnosed multiple myeloma patients. Leukemia. 2021 Sep;35(9):2715-2719. doi: 10.1038/s41375-021-01162-z. Epub 2021 Feb 15. No abstract available. |
| 31127403 | Background | Antoine-Pepeljugoski C, Braunstein MJ. Management of Newly Diagnosed Elderly Multiple Myeloma Patients. Curr Oncol Rep. 2019 May 24;21(7):64. doi: 10.1007/s11912-019-0804-4. |
| 31099676 | Background | Mina R, Bringhen S, Wildes TM, Zweegman S, Rosko AE. Approach to the Older Adult With Multiple Myeloma. Am Soc Clin Oncol Educ Book. 2019 Jan;39:500-518. doi: 10.1200/EDBK_239067. Epub 2019 May 17. |
| 32601004 | Background | Joao C, Geraldes C, Neves M, Mariz M, Trigo F. Management of older and frail patients with multiple myeloma in the Portuguese routine clinical practice: Deliberations and recommendations from an expert panel of hematologists. J Geriatr Oncol. 2020 Nov;11(8):1210-1216. doi: 10.1016/j.jgo.2020.06.002. Epub 2020 Jun 27. |
| 37164972 | Background | Mian H, Wildes TM, Vij R, Pianko MJ, Major A, Fiala MA. Dynamic frailty risk assessment among older adults with multiple myeloma: A population-based cohort study. Blood Cancer J. 2023 May 10;13(1):76. doi: 10.1038/s41408-023-00843-5. |
| 35114152 | Background | Raje NS, Anaissie E, Kumar SK, Lonial S, Martin T, Gertz MA, Krishnan A, Hari P, Ludwig H, O'Donnell E, Yee A, Kaufman JL, Cohen AD, Garderet L, Wechalekar AF, Terpos E, Khatry N, Niesvizky R, Yi Q, Joshua DE, Saikia T, Leung N, Engelhardt M, Mothy M, Branagan A, Chari A, Reiman AJ, Lipe B, Richter J, Rajkumar SV, Miguel JS, Anderson KC, Stadtmauer EA, Prabhala RH, McCarthy PL, Munshi NC. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol. 2022 Feb;9(2):e143-e161. doi: 10.1016/S2352-3026(21)00283-0. |
| 35440057 | Background | Encinas C, Hernandez-Rivas JA, Oriol A, Rosinol L, Blanchard MJ, Bellon JM, Garcia-Sanz R, de la Rubia J, de la Guia AL, Jimenez-Ubieto A, Jarque I, Inigo B, Dourdil V, de Arriba F, Perez-Avila CC, Gonzalez Y, Hernandez MT, Bargay J, Granell M, Rodriguez-Otero P, Silvent M, Cabrera C, Rios R, Alegre A, Gironella M, Gonzalez MS, Sureda A, Sampol A, Ocio EM, Krsnik I, Garcia A, Garcia-Mateo A, Soler JA, Martin J, Arguinano JM, Mateos MV, Blade J, San-Miguel JF, Lahuerta JJ, Martinez-Lopez J; GEM/PETHEMA (Grupo Espanol de Mieloma/Programa para el Estudio de la Terapeutica en Hemopatias Malignas) cooperative study group. A simple score to predict early severe infections in patients with newly diagnosed multiple myeloma. Blood Cancer J. 2022 Apr 19;12(4):68. doi: 10.1038/s41408-022-00652-2. |
| 38915117 | Derived | Zhang Y, Liang X, Xu W, Yi X, Hu R, Ma X, Yan Y, Zhang N, Wang J, Sun X, Zhu Y, Tian M, Lan M, Long M, Dai Y, Jin F. Individualized dynamic frailty-tailored therapy (DynaFiT) in elderly patients with newly diagnosed multiple myeloma: a prospective study. J Hematol Oncol. 2024 Jun 24;17(1):48. doi: 10.1186/s13045-024-01569-y. |
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |