Patients non-eligible for transplant

ASH 2017 | Bortezomib and lenalidomide induction regimens for high-risk transplant-ineligible NDMM patients

On Monday 11 December 2017, an oral abstract session was held entitled: Session: 653. Myeloma: Therapy, excluding Transplantation I. The talk was presented by Alessandra Larocca from the Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy and entitled: Abstract 744: Impact of Bortezomib- or Lenalidomide-Based Induction Treatment on High Risk Cytogenetic Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Enrolled in the Gimema-MM-03-05 and EMN01 Trials. This study assessed the impact of cytogenetics on outcomes in transplant-ineligible patients with newly diagnosed MM (NDMM) treated with bortezomib-based induction (BORT) or lenalidomide-based (LEN) treatment.

In the GIMEMA-MM-03-05-trial, patients (pts) were randomized to bortezomib-melphalan-prednisone-thalidomide for 9 cycles followed by maintenance with bortezomib-thalidomide (VMPT-VT) and compared to bortezomib-melphalan-prednisone (VMP) for 9 cycles, without maintenance. In the EMN01-trial, patients were randomized to melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus low-dose dexamethasone (Rd) for 9 cycles, followed by maintenance with either lenalidomide alone or lenalidomide plus prednisone continuously.

Key Findings:
  • VMP vs Rd (≤ 75 yrs):
    • Median PFS: 24.8 vs 18.8 months, HR = 0.77 (95% Cl, 0.60–0.99, P =0.04)
    • Median OS (4 yrs):  65% vs 59%, HR = 0.69 (95% Cl, 0.49–0.96, P =0.03)
  • VMP vs Rd (> 75 yrs):
    • Median PFS: 27.5 vs 17.8 months, HR = 0.93 (95% Cl, 0.61–1.41, P =0.72)
    • Median OS (4 yrs):  49% vs 54%, HR = 1.44 (95% Cl, 0.87–2.38, P =0.15)
  • Median follow-up for both arms: Gimema-MM-03-05 (BORT-based) - 72.3 months; EMN01 (LEN-based) = 65.8 months
  • Median age of pts: BORT = 71 yrs; LEN = 73 yrs
  • Pts were characterized via cytogenetic risk group according to IMWG consensus:
    • High-risk: del(17p) ≥10% or t(4;14) ≥15% or t(14;16) ≥15%
    • Standard-risk group: all other pts
  • Median follow-up is 69.9 months for VMP vs VMPT vs Rd vs CPR vs MPR
Treatments Median PFS (months) Median OS (months)
VMPT 33.8 NR
VMP 25.1 71
Rd 18.6 62
CPR 18.9 67.5
MPR 22.2 66.2
  • There is a higher PFS in VMPT-treated pts and a higher OS in LEN-based pts
  • Data for standard-risk subset of MM patients (BORT vs LEN):
  • Median PFS (29.1 vs 21.7 months), HR = 0.84 (95% Cl, 0.70–1.01, P =0.07)
  • Median OS (78.1 vs 79.9 months), HR = 1.03 (95% Cl, 0.80–1.32, P =0.81)
  • Data for high-risk subset of MM patients (BORT vs LEN):
    • Median PFS (30.8 vs 14.8 months), HR = 0.54 (95% Cl, 0.41–0.72, P <0.001)
    • Median OS (62.4 vs 43.2 months), HR = 0.65 (95% Cl, 0.45–0.92, P =0.02)
  • Pts with combined lesions were identified having one or more of the following cytogenetic abnormalities: t(4;14) or t(14;16) or del(17p)
  • Data for Combined lesions (BORT vs LEN):
  • 1 abnormality
    • Median PFS (31.5 vs 15.1 months), HR = 0.54 (95% Cl, 0.39-0.74, P <0.001)
    • Median OS (61 vs 44%), HR = 0.71 (95% Cl, 0.48-1.05, P =0.09)
  • ≥ 2 abnormalities:
    • Median PFS (19.8 vs 11.8 months), HR = 0.51 (95% Cl, 0.25-1.03, P =0.03)
    • Median OS (63 vs 33%), HR = 0.37 (95% Cl, 0.15-0.90, P =0.03)
  • Data for chromosomal abnormalities (BORT vs LEN):
  • Del17p
    • Median PFS: 18 vs 13 months, HR = 0.72 (95% Cl, 0.49-1.05, P =0.09)
    • Median OS: 56 vs 43%, HR = 0.75 (95% Cl, 0.47-1.20, P =0.23)
  • t(4;14)
    • Median PFS: 32 vs 15 months, HR = 0.41 (95% Cl, 0.27-0.61, P <0.001)
    • Median OS: 63 vs 43%, HR = 0.56 (95% Cl, 0.33-0.94, P =0.03)
  • t(14;16)
    • Median PFS: 36 vs 10 months, HR = 0.34 (95% Cl, 0.16-0.75, P =0.008)
    • Median OS: 86 vs 31%, HR = 0.14 (95% Cl, 0.05-0.45, P <0.001)

Dr. Larocca concluded that BORT-based treatments (i.e VMP) displayed an advantage for high-risk NDMM patients that are ineligible for transplant. In standard-risk patients, the choice of treatment should be based upon comorbidities (such as renal impairment), fitness/age, compliance and patient preference. Additionally, the study detected a higher overall survival in patients over the age of 75 years of age, when administered LEN-based treatments. It was suggested that FISH analysis should be performed in all NDMM for risk stratification and that better treatment options and newer combinations in the high-risk subtype, as classified in this study, are needed.

References
  1. Larocca et al. Impact of Bortezomib- or Lenalidomide-Based Induction Treatment on High Risk Cytogenetic Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Enrolled in the Gimema-MM-03-05 and EMN01 Trials. #Abstract 744. 59th ASH Annual Meeting and Exposition 2017, December 2017, Atlanta, GA.