Treatment Intensification With Autologous Stem Cell Transplantation and Lenalidomide Maintenance Improves Survival Outcomes of Patients With Newly Diagnosed Multiple Myeloma in Complete Response

Clin Lymphoma Myeloma Leuk. 2018 Aug;18(8):533-540. doi: 10.1016/j.clml.2018.05.019. Epub 2018 May 28.

Abstract

Background: High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy.

Patients and methods: We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m).

Results: Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy.

Conclusion: Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy.

Keywords: ASCT; CR; Lenalidomide; MM; Treatment intensification.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Clinical Trials, Phase III as Topic
  • Consolidation Chemotherapy
  • Female
  • Humans
  • Lenalidomide / administration & dosage*
  • Lenalidomide / adverse effects
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Neoplasm, Residual
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Stem Cell Transplantation* / adverse effects
  • Stem Cell Transplantation* / mortality
  • Time Factors
  • Transplantation, Autologous

Substances

  • Antineoplastic Agents, Alkylating
  • Lenalidomide