{"title":"新诊断的高风险多发性骨髓瘤患者的当前管理方法。","authors":"Naimisha Marneni, Rajshekhar Chakraborty","doi":"10.1007/s11899-021-00631-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>With rapid advances in the therapeutic landscape and biological insights in multiple myeloma, it is critical to identify and strategically manage high-risk patients to achieve best outcomes with currently available drugs. The purpose of this review is to summarize the management of high-risk myeloma with a focus on recent advances in the field.</p><p><strong>Recent findings: </strong>The most widely accepted definition of \"high-risk\" is the Revised International Staging System (R-ISS) stage 3 disease, which includes high tumor burden (ISS stage 3) and high-risk FISH cytogenetics or an elevated lactate dehydrogenase level. A major advance in the management of high-risk patients is insight into the importance of achieving and sustaining minimal residual disease (MRD) negativity, which is an influential equalizer for long-term outcomes. Quadruplet pre-transplant induction regimens incorporating an anti-CD38 monoclonal antibody (mAb), proteasome inhibitor (PI: bortezomib or carfilzomib), lenalidomide, and dexamethasone should be strongly considered in high-risk patients given higher odds of getting to MRD negativity with these regimens compared to triplets. In transplant-eligible patients, upfront transplant does lead to a higher rate of sustained MRD negativity and superior PFS compared to delayed transplant. The role of tandem transplant in the context of bortezomib-lenalidomide-dexamethasone (VRD) induction therapy is unclear. Post-transplant maintenance therapy should include lenalidomide in combination with either bortezomib or carfilzomib until progression. For transplant-ineligible patients, VRD or daratumumab-lenalidomide-dexamethasone (DRD) until progressions are both reasonable and choice should be individualized based on patient-related factors. Outcomes of high-risk myeloma patients have improved in the last decade with the use of modern 3-drug induction regimens incorporating a PI and an immunomodulatory drug, with potential for further improvement as we bring anti-CD38 mAb upfront. MRD assessment will play a major role in treatment modification at several key time-points in the future such as pre-transplant, pre-maintenance, and yearly on maintenance therapy.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00631-7","citationCount":"2","resultStr":"{\"title\":\"Current Approach to Managing Patients with Newly Diagnosed High-Risk Multiple Myeloma.\",\"authors\":\"Naimisha Marneni, Rajshekhar Chakraborty\",\"doi\":\"10.1007/s11899-021-00631-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>With rapid advances in the therapeutic landscape and biological insights in multiple myeloma, it is critical to identify and strategically manage high-risk patients to achieve best outcomes with currently available drugs. The purpose of this review is to summarize the management of high-risk myeloma with a focus on recent advances in the field.</p><p><strong>Recent findings: </strong>The most widely accepted definition of \\\"high-risk\\\" is the Revised International Staging System (R-ISS) stage 3 disease, which includes high tumor burden (ISS stage 3) and high-risk FISH cytogenetics or an elevated lactate dehydrogenase level. A major advance in the management of high-risk patients is insight into the importance of achieving and sustaining minimal residual disease (MRD) negativity, which is an influential equalizer for long-term outcomes. Quadruplet pre-transplant induction regimens incorporating an anti-CD38 monoclonal antibody (mAb), proteasome inhibitor (PI: bortezomib or carfilzomib), lenalidomide, and dexamethasone should be strongly considered in high-risk patients given higher odds of getting to MRD negativity with these regimens compared to triplets. In transplant-eligible patients, upfront transplant does lead to a higher rate of sustained MRD negativity and superior PFS compared to delayed transplant. The role of tandem transplant in the context of bortezomib-lenalidomide-dexamethasone (VRD) induction therapy is unclear. Post-transplant maintenance therapy should include lenalidomide in combination with either bortezomib or carfilzomib until progression. For transplant-ineligible patients, VRD or daratumumab-lenalidomide-dexamethasone (DRD) until progressions are both reasonable and choice should be individualized based on patient-related factors. Outcomes of high-risk myeloma patients have improved in the last decade with the use of modern 3-drug induction regimens incorporating a PI and an immunomodulatory drug, with potential for further improvement as we bring anti-CD38 mAb upfront. MRD assessment will play a major role in treatment modification at several key time-points in the future such as pre-transplant, pre-maintenance, and yearly on maintenance therapy.</p>\",\"PeriodicalId\":10852,\"journal\":{\"name\":\"Current Hematologic Malignancy Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2021-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1007/s11899-021-00631-7\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Hematologic Malignancy Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11899-021-00631-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/4/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Hematologic Malignancy Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11899-021-00631-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/4/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Current Approach to Managing Patients with Newly Diagnosed High-Risk Multiple Myeloma.
Purpose of review: With rapid advances in the therapeutic landscape and biological insights in multiple myeloma, it is critical to identify and strategically manage high-risk patients to achieve best outcomes with currently available drugs. The purpose of this review is to summarize the management of high-risk myeloma with a focus on recent advances in the field.
Recent findings: The most widely accepted definition of "high-risk" is the Revised International Staging System (R-ISS) stage 3 disease, which includes high tumor burden (ISS stage 3) and high-risk FISH cytogenetics or an elevated lactate dehydrogenase level. A major advance in the management of high-risk patients is insight into the importance of achieving and sustaining minimal residual disease (MRD) negativity, which is an influential equalizer for long-term outcomes. Quadruplet pre-transplant induction regimens incorporating an anti-CD38 monoclonal antibody (mAb), proteasome inhibitor (PI: bortezomib or carfilzomib), lenalidomide, and dexamethasone should be strongly considered in high-risk patients given higher odds of getting to MRD negativity with these regimens compared to triplets. In transplant-eligible patients, upfront transplant does lead to a higher rate of sustained MRD negativity and superior PFS compared to delayed transplant. The role of tandem transplant in the context of bortezomib-lenalidomide-dexamethasone (VRD) induction therapy is unclear. Post-transplant maintenance therapy should include lenalidomide in combination with either bortezomib or carfilzomib until progression. For transplant-ineligible patients, VRD or daratumumab-lenalidomide-dexamethasone (DRD) until progressions are both reasonable and choice should be individualized based on patient-related factors. Outcomes of high-risk myeloma patients have improved in the last decade with the use of modern 3-drug induction regimens incorporating a PI and an immunomodulatory drug, with potential for further improvement as we bring anti-CD38 mAb upfront. MRD assessment will play a major role in treatment modification at several key time-points in the future such as pre-transplant, pre-maintenance, and yearly on maintenance therapy.
期刊介绍:
his journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of hematologic malignancy.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as leukemia, lymphoma, myeloma, and T-cell and other lymphoproliferative malignancies. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.