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ATLAS: intensified maintenance strategy after autologous HSCT in multiple myeloma.

In this phase 3 trial, carfilzomib–lenalidomide–dexamethasone maintenance prolonged progression-free survival versus lenalidomide alone; the authors describe evidence for improved overall survival and note subgroup benefit in MRD-positive and high-risk-cytogenetics patients that may inform future risk-adapted approaches.

  • Dominik Dytfeld, MD; Tomasz Wróbel, MD; Krzysztof Jamroziak, MD; Tadeusz Kubicki, MD; Paweł Robak, MD; Anna Puła, MD; et al.

  • March 11, 2026

  • The Lancet Haematology
  • The Lancet Haematology, Volume 13, Issue 4, Pages e241–e253
  • 10.1016/S2352-3026(26)00011-6

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Evidence before this study

We searched PubMed for articles published in English between Jan 1, 2010, and Oct 1, 2025, using the terms “multiple myeloma”, “autologous transplantation”, “maintenance therapy”, “carfilzomib”, “lenalidomide”, “dexamethasone”, and “randomised trial”. This search identified several key maintenance studies. Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation (HSCT) has consistently prolonged progression-free survival and, in some studies, overall survival, establishing it as a global standard of care. The CASSIOPEIA trial showed that daratumumab maintenance after daratumumab–bortezomib–thalidomide–dexamethasone induction reduced the risk of progression compared with observation. In FORTE, maintenance with carfilzomib plus lenalidomide improved progression-free survival compared with lenalidomide alone, particularly in patients with high-risk cytogenetics. AURIGA confirmed that daratumumab–lenalidomide maintenance improved measurable residual disease (MRD) negativity rates and progression-free survival versus lenalidomide alone. Despite these advances, evidence for intensified or MRD-adapted maintenance strategies beyond lenalidomide alone remained limited.

Added value of this study

To our knowledge, ATLAS is the first randomised, phase 3 trial to directly compare carfilzomib–lenalidomide–dexamethasone maintenance with lenalidomide alone after autologous HSCT, independent of the induction regimen used. With long-term follow-up, ATLAS shows that carfilzomib–lenalidomide–dexamethasone maintenance significantly prolongs progression-free survival and provides evidence for improved overall survival compared with lenalidomide alone, with clear benefit in MRD-positive patients and higher MRD negativity rates in those with high-risk cytogenetics. Importantly, the protocol incorporated MRD-guided de-escalation, providing unique evidence on tailoring maintenance intensity.

Implications of all the available evidence

When considered alongside CASSIOPEIA, FORTE, and AURIGA, the results of the ATLAS trial strengthen the case for moving beyond uniform lenalidomide monotherapy toward risk-adapted and MRD-adapted maintenance. Intensified regimens such as carfilzomib–lenalidomide–dexamethasone might be particularly relevant for patients with high-risk features or persistent MRD, helping refine maintenance as a personalised strategy in the modern myeloma treatment landscape.

Source: The Lancet Haematology

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