EBMT 2018 | Impact of cytogenetics on transplant outcome in MM patients with EMD

The MM Hub were delighted to attend the 44^th Annual Meeting of the European Society for Blood and Marrow Transplantation held in Lisbon, Portugal, from 18–21 March 2018. On Monday 19 March 2018 the oral abstract session 4 was held. The session was moderated by Catarina Geraldes, from the Department of Clinical Hematology, University of Coimbra, Portugal and Tamás Masszi, the Department of Internal Medicine, Semmelweis University, Budapest, Hungary. The first talk in this session was presented by Nico Gagelmann, from the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany, on the topic of Impact of cytogenetics on outcome after stem-cell transplantation in multiple myeloma with extramedullary disease: an analysis of the CMWP-WBMT. 

Demographics:

• Identification of 488 patients (pts) in the EBMT registry, between 2013–2015:
  • Upfront single auto = 373 pts
  • Tandem-autologous (tandem-auto) = 84 pts
  • Autologous/reduced-intensity allogeneic (auto-allo) = 31 pts
  • Extramedullary disease (EMD) was defined as manifestations resulting from bone lesions (paraskeletal = 376 pts) or hematogenous spread into different organs = 85 pts; both combined = 27 pts
• ISS: stage I = 224 pts; stage II = 140 pts and stage III = 124 pts
• Normal cytogenetic risk = 286 pts
• High-risk cytogenetics defined as the presence of one of the following abnormalities (202 pts): del(17p) = 81 pts; t(4;14) = 90 pts;  t(14;16) = 13 pts; t(14;20) = 6 pts, and abnormal (1) =50 pts
• Ig subtypes: IgG = 231 pts; IgA = 106 pts; light chain = 120 pts; other = 8 pts
• Median time to first transplant = 6 months (range 2­–11)
• Stages at transplant: complete response (CR) = 107 pts; < CR = 381 pts
• Median age (years) and % of pts with high-risk cytogenetics, for different treatments: single-auto = 60 yrs and 37%; tandem-auto = 60 yrs and 44%; auto-allo = 49 yrs and 52%
• CR (before transplant): single-auto = 24%; tandem-auto = 13%; auto-allo = 19%
• Median follow-up = 49.3 months

Key findings:

• High-risk cytogenetics vs normal:
  • 4-year progression-free survival (PFS) = 29.0% (95% CI, 20.2–37.8) vs 48.6% (41.5–55.7); P < 0.001
  • 4-year overall survival (OS) = 50.2% (42.0–58.4) vs 77.4% (71.9–82.9); P < 0.001
• Disease site (paraskeletal vs organ vs both):
  • 4-year PFS = 43.6% (37.3–49.9) vs 38.3% (25.4–51.2) vs 19.7% (0–41.7)
  • 4-year OS = 70.6% (65.3–75.9) vs 55.1% (42.8–67.4) vs 47 (25.2–68.8)
• Transplantation (single-auto vs tandem-auto vs auto-allo):
  • 4-year PFS = 38.3% (32.0–44.6) vs 51.5% (39.3–63.7) vs 60.7% (32.7–88.7)
  • 4-year OS = 62.1% (56.2–68.0) vs 77.8% (68.4–87.2) vs 81.1% (66.0-96.2); P = 0.018
• Tandem-auto vs auto-allo vs single-auto:
  • Incidence of relapse at 4-years (%) = 47.1 vs 37.1 vs 58.8 (P = 0.21)
  • Incidence of non-relapse at 4-years (%) = 1.4 vs 8.6 vs 3.0 (P = 0.14)
• Tandem-auto and cytogenetics (normal vs high-risk):
  • 4-year PFS = 53.6% (37.7–69.5) vs 50.4% (31.6–69.2)
  • 4-year OS = 80.8% (68.1–92.7) vs 80.4% (66.9–94.7)
• Single-auto and cytogenetics (normal vs high-risk):
  • 4-year PFS = 47.7% (38.3–58.1) vs 22.0% (11.2–35.0); P < 0.001
  • 4-year OS = 76.2% (69.3–82.1) vs 40.7% (30.3–49.8); P < 0.001
• Significant improvement in patients with EMD and high-risk cytogenetics in all treatment groups
• Multivariate analysis for tandem-auto:
  • PFS: Hazard ratio (HR) = 0.55 (0.38–0.82); P = 0.003
  • OS: HR = 0.31 (0.17–0.58); P < 0.001
• Multivariate analysis for high-risk cytogenetics:
  • PFS: HR = 1.80 (1.36–2.37); P < 0.001
  • OS: HR = 3.02 (2.10–4.36); P < 0.001
• Multivariate analysis for light chain:
  • PFS: HR = 1.45 (1.02–2.06); P = 0.04
• Multivariate analysis for no of involvement (> 1):
  • PFS: HR = 2.09 (1.35–3.24); P = 0.001

This analysis supports the beneficial use of tandem-autologous transplantation, to improve the OS and prognosis of NDMM patients with high-risk cytogenetics. The study also highlights the potential influence that EMD-specific factors (such as light chain, the number of involved sites, and paraskeletal involvement) can have on a patient’s prognosis.