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The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long‐term follow‐up results from BSBMT / UKMF Myeloma X Relapse [Intensive]): a randomised, open‐label, phase 3 trial
Author(s) -
Cook Gordon,
Royle KaraLouise,
O'Connor Sheila,
Cairns David A.,
Ashcroft A. John,
Williams Cathy D.,
Hockaday Anna,
Cavenagh Jamie D.,
Snowden John A.,
Ademokun Debo,
Tholouli Eleni,
Andrews Vivienne E.,
Jenner Matthew,
Parrish Christopher,
Yong Kwee,
Cavet Jim,
Hunter Hannah,
Bird Jenny M.,
Pratt Guy,
Drayson Mark T.,
Brown Julia M.,
Morris Treen C. M.
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15782
Subject(s) - medicine , hazard ratio , multiple myeloma , cyclophosphamide , autologous stem cell transplantation , oncology , confidence interval , surgery , chemotherapy , gastroenterology
Summary The Myeloma X trial ( ISCRTN 60123120) registered patients with relapsed multiple myeloma. Participants were randomised between salvage autologous stem cell transplantation ( ASCT ) or weekly cyclophosphamide following re‐induction therapy. Cytogenetic analysis performed at trial registration defined t(4;14), t(14;16) and del(17p) as high‐risk. The effect of cytogenetics on time to progression ( TTP ) and overall survival was investigated. At 76 months median follow‐up, ASCT improved TTP compared to cyclophosphamide (19 months (95% confidence interval [95% CI] 16–26) vs. 11 months (9–12), hazard ratio [ HR ]: 0·40, 95% CI: 0·29–0·56, P < 0·001), on which the presence of any single high‐risk lesion had a detrimental impact [likelihood ratio test ( LRT ): P = 0·011]. ASCT also improved OS [67 months (95% CI 59‐not reached) vs. 55 months (44–67), HR : 0·64, 95% CI: 0·42–0·99, P = 0·0435], with evidence of a detrimental impact with MYC rearrangement ( LRT : P = 0·021). Twenty‐one (24·7%) cyclophosphamide patients received an ASCT post‐trial, median OS was not reached (95% CI: 39‐not reached) for these participants compared to 31 months (22–39), in those who did not receive a post‐trial ASCT . The analysis further supports the benefit of salvage ASCT , which may still be beneficial after second relapse in surviving patients. There is evidence that this benefit reduces in cytogenetic high‐risk patients, highlighting the need for targeted study in this patient group.