Full or intensity-reduced high-dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma

Eur J Haematol. 2021 Nov;107(5):529-542. doi: 10.1111/ejh.13690. Epub 2021 Aug 28.

Abstract

Objective: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed.

Methods: Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.6 mg/m² IV on days 1, 8, 15, 22) or observation.

Results: Of the 340 patients included in this analysis, 13.5% received 1 × MEL100/140, 22.9% 2 × MEL100/140, 31.2% 1 × MEL200, and 32.4% 2 × MEL200. With higher cumulative melphalan dose, PFS improved (P = .0085). PFS curves of patients treated with 2 × MEL100/140 and 1 × MEL200 were very similar. The superior dose effect of MEL200 over MEL100/140 was non-existent in the bortezomib consolidation arm but pronounced in the observation arm (P = .0015). Similarly, double ASCT was only beneficial in patients without bortezomib consolidation (P = .0569).

Conclusions: Full dose melphalan and double transplantation seem advantageous only as long as patients are not receiving bortezomib consolidation afterwards.

Keywords: ASCT; OS; PFS; bortezomib; consolidation; high-dose melphalan 100/140 mg/m² or 200 mg/m²; multiple myeloma.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / administration & dosage*
  • Combined Modality Therapy
  • Consolidation Chemotherapy / methods*
  • Dose-Response Relationship, Drug
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Male
  • Melphalan / administration & dosage*
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / therapy*
  • Retrospective Studies
  • Transplantation, Autologous

Substances

  • Bortezomib
  • Melphalan

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