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Article: Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond

TitleManagement of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond
Authors
Issue Date2018
PublisherSpringer Nature [academic journals on nature.com]: Hybrid Journals. The Journal's web site is located at http://www.nature.com/leu
Citation
Leukemia, 2018, v. 32 n. 2, p. 252-262 How to Cite?
AbstractDespite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23.6 months (ASPIRE). Based on these RCTs, next-generation proteasome inhibitors (carfilzomib and ixazomib), next-generation immunomodulatory agent (pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) were approved for relapsed and refractory MM. Daratumumab, targeting CD38, has multiple mechanisms of action including modulation of the immunosuppressive bone marrow micro-environment. In addition to the remarkable single agent activity in refractory MM, daratumumab produced deep responses and superior PFS in MM when combined with lenalidomide/dexamethasone, or bortezomib/dexamethasone. Other anti-CD38 antibodies, such as isatuximab and MOR202, are undergoing assessment. Elotuzumab, targeting SLAMF7, yielded superior response rates and PFS when combined with lenalidomide/dexamethasone. New combinations of these next generation novel agents and/or antibodies are undergoing clinical trials. Venetoclax, an oral BH3 mimetic inhibiting BCL2, showed single agent activity in MM with t(11;14), and is being studied in combination with bortezomib/dexamethasone. Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. Pembrolizumab, an anti-PD1 check-point inhibitor, is being tested in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone. Chimeric antigen receptor-T cells targeting B-cell maturation antigen have yielded deep responses in RRMM. Finally, salvage autologous stem cell transplantation (ASCT) remains an important treatment in MM relapsing/progressing after a first ASCT. Herein, the clinical trial data of these agents are summarized, cautious interpretation of RCTs highlighted, and algorithm for salvage treatment of relapse/refractory MM proposed.
Persistent Identifierhttp://hdl.handle.net/10722/271994
ISSN
2019 Impact Factor: 8.665
2015 SCImago Journal Rankings: 5.142
PubMed Central ID
ISI Accession Number ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorChim, CS-
dc.contributor.authorKumar, SK-
dc.contributor.authorOrlowski, RZ-
dc.contributor.authorCook, G-
dc.contributor.authorRichardson, PG-
dc.contributor.authorGertz, MA-
dc.contributor.authorGiralt, S-
dc.contributor.authorMateos, MV-
dc.contributor.authorLeleu, X-
dc.contributor.authorAnderson, KC-
dc.date.accessioned2019-07-20T10:33:36Z-
dc.date.available2019-07-20T10:33:36Z-
dc.date.issued2018-
dc.identifier.citationLeukemia, 2018, v. 32 n. 2, p. 252-262-
dc.identifier.issn0887-6924-
dc.identifier.urihttp://hdl.handle.net/10722/271994-
dc.description.abstractDespite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23.6 months (ASPIRE). Based on these RCTs, next-generation proteasome inhibitors (carfilzomib and ixazomib), next-generation immunomodulatory agent (pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) were approved for relapsed and refractory MM. Daratumumab, targeting CD38, has multiple mechanisms of action including modulation of the immunosuppressive bone marrow micro-environment. In addition to the remarkable single agent activity in refractory MM, daratumumab produced deep responses and superior PFS in MM when combined with lenalidomide/dexamethasone, or bortezomib/dexamethasone. Other anti-CD38 antibodies, such as isatuximab and MOR202, are undergoing assessment. Elotuzumab, targeting SLAMF7, yielded superior response rates and PFS when combined with lenalidomide/dexamethasone. New combinations of these next generation novel agents and/or antibodies are undergoing clinical trials. Venetoclax, an oral BH3 mimetic inhibiting BCL2, showed single agent activity in MM with t(11;14), and is being studied in combination with bortezomib/dexamethasone. Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. Pembrolizumab, an anti-PD1 check-point inhibitor, is being tested in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone. Chimeric antigen receptor-T cells targeting B-cell maturation antigen have yielded deep responses in RRMM. Finally, salvage autologous stem cell transplantation (ASCT) remains an important treatment in MM relapsing/progressing after a first ASCT. Herein, the clinical trial data of these agents are summarized, cautious interpretation of RCTs highlighted, and algorithm for salvage treatment of relapse/refractory MM proposed.-
dc.languageeng-
dc.publisherSpringer Nature [academic journals on nature.com]: Hybrid Journals. The Journal's web site is located at http://www.nature.com/leu-
dc.relation.ispartofLeukemia-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleManagement of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond-
dc.typeArticle-
dc.identifier.emailChim, CS: jcschim@hku.hk-
dc.identifier.authorityChim, CS=rp00408-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/leu.2017.329-
dc.identifier.pmid29257139-
dc.identifier.pmcidPMC5808071-
dc.identifier.scopuseid_2-s2.0-85042354801-
dc.identifier.hkuros299556-
dc.identifier.volume32-
dc.identifier.issue2-
dc.identifier.spage252-
dc.identifier.epage262-
dc.identifier.isiWOS:000424517300002-
dc.publisher.placeUnited Kingdom-
dc.relation.erratumdoi:10.1038/s41375-019-0410-3-
dc.relation.erratumeid:eid=2-s2.0-85062627472-

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