Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study

Autores de IIS La Fe

• Carmen Salvador Coloma

  Autor

• 

  Javier De La Rubia Comos

  Autor

• Javier López Davia

  Autor

Participantes ajenos a IIS La Fe

• Mateos M.-V.
• Hernández M.-T.
• de Arriba F.
• López-Corral L.
• Rosiñol L.
• Paiva B.
• Palomera L.
• Bargay J.
• Oriol A.
• Prosper F.
• Arguiñano J.-M.
• Bladé J.
• Lahuerta J.-J.
• San-Miguel J.

Grupos

• Dermatología y Regeneración Tisular

• Hematología y Hemoterapia

Abstract

Background: Smoldering multiple myeloma (SMM) is a heterogeneous disease in terms of progression to myeloma (MM), but its standard of care continues to be observation. Methods: The QuiRedex phase 3 trial initiated in 2007 included 119 high-risk patients with SMM randomized to treatment or observation. Treatment consisted of nine 4-week induction cycles (lenalidomide [Rd], 25 mg on days 1–21 plus dexamethasone, 20 mg on days 1–4 and 12–15), followed by maintenance (R, 10 mg on days 1–21) for up to 2 years. The primary end-point was time to progression (TTP) to myeloma based on per protocol population. Secondary end-points were overall survival (OS), response rate, and safety. An update of the trial after a long-term follow-up is presented here. This trial was registered with ClinicalTrials.gov (NCT00480363). Findings: After a median follow-up time of 12.5 years (range: 10.4–13.6), the median TTP to MM was 2.1 years in the observation arm and 9.5 years in the Rd arm (HR: 0.28, 95% CI: 0.18–0.44, p < 0.0001). The median OS was 8.5 years in the abstention arm and not reached in the Rd group (HR: 0.57, 95% CI: 0.34–0.95, p = 0.032). Patients who progressed received optimized treatments according to the standards of care, and the OS from progression was comparable in both arms (p = 0.96). Interpretation: This analysis confirms that early treatment with Rd for high-risk SMM translates into a sustained benefit in both TTP and OS. Funding: Pethema (Spanish Program for the Treatment of Hematologic Diseases), Spain. © 2022 Elsevier Ltd

Keywords

• Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Follow-Up Studies; Humans; Lenalidomide; Multiple Myeloma; Smoldering Multiple Myeloma; Thiamine; dexamethasone; lenalidomide; antineoplastic agent; dexamethasone; lenalidomide; thiamine; thiamine triphosphorate; adult; Article; cancer growth; cancer patient; cancer survival; controlled study; disease free interval; female; follow up; health care quality; high risk patient; human; major clinical study; male; open study; overall survival; phase 3 clinical trial; randomized controlled trial; smoldering multiple myeloma; multiple myeloma; smoldering multiple myeloma