Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 192, Issue 5, Pages 853-868Publisher
WILEY
DOI: 10.1111/bjh.16945
Keywords
myeloma; transplant‐ ineligible; lenalidomide; thalidomide; immunomodulatory agent
Categories
Funding
- Cancer Research UK [C1298/A10410] Funding Source: Medline
- Celgene Corporation Funding Source: Medline
- Merck Funding Source: Medline
- Royal Marsden Funding Source: Medline
- University of Leeds Funding Source: Medline
- Institute of Cancer Research Funding Source: Medline
- Myeloma UK Funding Source: Medline
- University of Birmingham Funding Source: Medline
- Cancer Research Institute Funding Source: Medline
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The Myeloma XI study compared the efficacy of thalidomide and lenalidomide in treating newly diagnosed transplant-ineligible myeloma patients, finding that CRDa had deeper responses for patients aged <= 70 years, but limited tolerability in older, frailer patients.
Second-generation immunomodulatory agents, such as lenalidomide, have a more favourable side-effect profile than the first-generation thalidomide, but their optimum combination and duration for patients with newly diagnosed transplant-ineligible myeloma (ND-TNE-MM) 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-TNE-MM. CRDa deepened response but did not improve progression-free (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 <= 70 years, 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-TNE-MM, highlighting the need for prospective validation of frailty adapted therapy approaches, which may improve outcomes by tailoring treatment to the individual.
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