{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:39:26Z","timestamp":1773830366732,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C1298\/A10410"],"award-info":[{"award-number":["C1298\/A10410"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011723","name":"Myeloma UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000884","name":"Cancer Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000777","name":"University of Leeds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000777","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000855","name":"University of Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012139","name":"Royal Marsden NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000027","name":"Institute of Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Second\u2010generation immunomodulatory agents, such as lenalidomide, have a more favourable side\u2010effect profile than the first\u2010generation thalidomide, but their optimum combination and duration for patients with newly diagnosed transplant\u2010ineligible myeloma (ND\u2010TNE\u2010MM) has not been defined. The most appropriate delivery and dosing regimens of these therapies for patients at advanced age and frailty status is also unclear. The Myeloma XI study compared cyclophosphamide, thalidomide and dexamethasone (CTDa) to cyclophosphamide, lenalidomide and dexamethasone (CRDa) as induction therapy, followed by a maintenance randomisation between ongoing therapy with lenalidomide or observation for patients with ND\u2010TNE\u2010MM. CRDa deepened response but did not improve progression\u2010free (PFS) or overall survival (OS) compared to CTDa. However, analysis by age group highlighted significant differences in tolerability in older, frailer patients that may have limited treatment delivery and impacted outcome. Deeper responses and PFS and OS benefits with CRDa over CTDs were seen in patients aged \u226470\u00a0years, with an increase in toxicity and discontinuation observed in older patients. Our results highlight the importance of considering age and frailty in the approach to therapy for patients with ND\u2010TNE\u2010MM, highlighting the need for prospective validation of frailty adapted therapy approaches, which may improve outcomes by tailoring treatment to the individual.<\/jats:p>","DOI":"10.1111\/bjh.16945","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T03:01:36Z","timestamp":1594609296000},"page":"853-868","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Optimising the value of immunomodulatory drugs during induction and maintenance in transplant ineligible patients with newly diagnosed multiple myeloma: results from Myeloma XI, a multicentre, open\u2010label, randomised, Phase III trial"],"prefix":"10.1111","volume":"192","author":[{"given":"Graham H.","family":"Jackson","sequence":"first","affiliation":[{"name":"Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7190-0028","authenticated-orcid":false,"given":"Charlotte","family":"Pawlyn","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research London UK"},{"name":"The Royal Marsden Hospital NHS Foundation Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2338-0179","authenticated-orcid":false,"given":"David A.","family":"Cairns","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit Leeds Institute of Clinical Trials Research University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Striha","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit Leeds Institute of Clinical Trials Research University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Collett","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit Leeds Institute of Clinical Trials Research University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Waterhouse","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit Leeds Institute of Clinical Trials Research University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Jones","sequence":"additional","affiliation":[{"name":"Kings College Hospital NHS Foundation Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Wilson","sequence":"additional","affiliation":[{"name":"Western Sussex Hospitals NHS Foundation Trust Chichester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Taylor","sequence":"additional","affiliation":[{"name":"Russells Hall Hospital Dudley UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhuvan","family":"Kishore","sequence":"additional","affiliation":[{"name":"University Hospitals Birmingham NHS Foundation Trust Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamta","family":"Garg","sequence":"additional","affiliation":[{"name":"Leicester Royal Infirmary Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy D.","family":"Williams","sequence":"additional","affiliation":[{"name":"Centre for Clinical Haematology Nottingham University Hospital Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamaraj","family":"Karunanithi","sequence":"additional","affiliation":[{"name":"University Hospital of North Midlands Stoke\u2010on\u2010Trent UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jindriska","family":"Lindsay","sequence":"additional","affiliation":[{"name":"E1ast Kent Hospitals University NHS Foundation Trust Canterbury UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew W.","family":"Jenner","sequence":"additional","affiliation":[{"name":"University Hospital Southampton NHS Foundation Trust Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-0412","authenticated-orcid":false,"given":"Gordon","family":"Cook","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit Leeds Institute of Clinical Trials Research University of Leeds Leeds UK"},{"name":"Leeds Cancer Centre University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel H.","family":"Russell","sequence":"additional","affiliation":[{"name":"Centre for Clinical Haematology Nottingham University Hospital Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T.","family":"Drayson","sequence":"additional","affiliation":[{"name":"Clinical Immunology Service Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3677-4804","authenticated-orcid":false,"given":"Martin F.","family":"Kaiser","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research London UK"},{"name":"The Royal Marsden Hospital NHS Foundation Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger G.","family":"Owen","sequence":"additional","affiliation":[{"name":"Haematological Malignancy Diagnostic Service (HMDS) St James's University Hospital Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter M.","family":"Gregory","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit Leeds Institute of Clinical Trials Research University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faith E.","family":"Davies","sequence":"additional","affiliation":[{"name":"Perlmutter Cancer Center NY Langone Health New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth J.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Perlmutter Cancer Center NY Langone Health New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"UK NCRI Haemato\u2010oncology Clinical Studies Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.119"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-338665"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3211"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-357038"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112704"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679415"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-08-662627"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70609-0"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402551"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.66.7295"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0595-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(18)30220-5"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30167-X"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30687-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.247130"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-019-03101-z"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31594-X"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714678"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32956-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817249"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-615187"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.16945","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.16945","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.16945","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.16945","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T10:56:19Z","timestamp":1693392979000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.16945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,12]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/bjh.16945"],"URL":"https:\/\/doi.org\/10.1111\/bjh.16945","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,12]]},"assertion":[{"value":"2020-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}