MCL

ASH 2018 | Eight-year follow up of GALGB 50403 (Alliance) phase II trial: Post-transplant bortezomib in MCL

On Saturday 1 December 2018, Oral Session 623 took place at the 60th American Society of Hematology (ASH) Annual Meeting, San Diego, CA. During that session, Abstract #146 with the results from the 8-year follow-up of the GALGB 50403 (Alliance) trial were presented by Lawrence Kaplan from the Helen Diller Family  Comprehensive Cancer Center, San Francisco, CA, USA.

GALGB 50403 (Alliance) was a phase II trial that investigated the efficacy and safety of adding post-transplant bortezomib consolidation (BC) or bortezomib maintenance (BM) in mantle cell lymphoma (MCL) patients. The primary analysis of the trial has previously reported a five-year progression-free survival (PFS) of 70% and 69% for BM and BC, respectively. Here the results from the 8-year follow-up of this trial were presented.

Study design & baseline characteristics
  • N = 147 histologically-confirmed MCL patients with CD20+, CD5+, CD23-, aged < 70, with evidence of cyclin D1 or bcl-1, t(11;14) were included in this analysis
  • Median patient age (range): 59 (29−69) years
  • Disease stage prior randomization:
    • Stage II/III: 14%
    • Stage IV: 86%
  • Mantle Cell Lymphoma International Prognostic Index (MIPI):
    • Low: 52%
    • Intermediate: 31%
    • High: 17%
  • Dosing:
    • Induction therapy: augmented R-CHOP for 2 or 3 cycles with 2000 mg/m2 cyclophosphamide and methotrexate 300 mg/m2 followed by high-dose cytarabine, etoposide, rituximab, filgrastim (EAR) stem cell mobilization and cyclophosphamide, carmustine, etoposide (CBV) autograft
    • After two doses of post-transplant rituximab (375 mg/m2), patients were randomized ~Day 90 to either:
      • BC:3 mg/m2 intravenously (IV) on Day 1, 4, 8, and 11 of a three-week cycle, for four cycles in total
      • BM:6 mg/m2 IV four times weekly every eight weeks for 18 months
    • Follow-up CT scans were performed every six months for two years from randomization
    • Minimal residual disease (MRD) was assessed every four months during BM or BC until two years after enrollment
    • Patients that were randomized: n = 102 (68%) [BC, n = 50; BM, n = 52]
    • Patients completing randomization treatment:
      • BC: n = 33 patients (66%)
      • BM: n = 34 patients (65%)
Results
  • With a median follow-up of 7.8 years, median PFS was:
    • BC: 8.9 years (95% CI, 7.2−not reached)
    • BM: not reached (95% CI, not reached−not reached)
  • With a median follow-up of 7.8 years, median overall survival (OS) was:
    • BC: 8.2 years (95% CI, 6.6−not reached)
    • BM: not reached (95% CI, 8.5−not reached)
  • With a median follow-up of 7.8 years, MRD status (n = 42 evaluable samples):
    • MRD negative: n = 17
    • MRD positive: n = 25
  • Eight-year PFS estimates:
    • BC: 58% (95% CI, 44−76%)
    • BM: 77% (95% CI, 66−90%)
  • There were more withdrawals due to adverse events with BC than BM
  • Patients completing randomization treatment:
    • BC: n = 33 patients (66%)
    • BM: n = 34 patients (65%)
  • Patient withdrawal due to adverse events (AEs):
    • BC: 28% of patients
    • BM: 13% of patients
    • Comparison: P = 0.09
  • Most common Grade ≥ 2 AEs observed (BC versus BM):
    • Neutropenia: 68% versus 50%
    • Thrombocytopenia: 50% versus 35%
    • Sensory neuropathy: 48% versus 29%
    • Fatigue: 40% versus 25%
Conclusions
  • Post-transplant therapy with bortezomib is feasible but associated with significant toxicity
  • MRD-negative post-induction was associated with better PFS and OS
  • There was an apparent patient benefit after transplant, which should encourage the development and study of more active, less toxic agents
  • The role of ASCT in post-induction MRD-negative patients is under investigation in a randomized clinical trial (EA4151)
References
  1. Kaplan D.L. et al. Bortezomib Maintenance (BM) or Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): 8 Year Follow up of CALGB 50403 (Alliance). Oral Session 623, Abstract #146: ASH 60th Annual Meeting and Exposition, December 2018, San Diego, CA
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