ASCT consolidation does not improve aggressive T-NHL patient outcomes

On 10 January 2019, Zeina Al-Mansour from the Cardinal Bernardin Cancer Center, Maywood, IL, USA, and colleagues, published in Leukemia & Lymphoma a retrospective analysis of aggressive T-cell non-Hodgkin lymphoma (T-NHL) patient data from the SWOG S9704 phase II trial.

In the SWOG S9704, phase II trial (NCT00004031), T-NHL patients received initially five cycles of either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP). Patients who responded to the initial treatment were randomized to either three additional cycles of chemotherapy or one cycle, followed by autologous stem cell transplantation (ASCT) with carmustine or total body irradiation (TBI). The aim of this secondary analysis was to evaluate the efficacy of consolidative ASCT after first remission in this aggressive T-NHL patient population.

Study design & baseline characteristics 

• N = 28 T-NHL patients from the SWOG S9704
• Patients who responded (even partial response) to five cycles of CHOP or R-CHOP were randomized to either consolidative ASCT (n = 15) or placebo (n = 13)
• Consolidative ASCT dosing:
  • Carmustine-based chemotherapy (n = 7): 300 mg/m² high-dose carmustine on Day -6 with 60 mg/kg high-dose etoposide on Day -4 and 100mg/kg high-dose cyclophosphamide on Day -2
  • TBI (n = 5): 12 Gy of radiation in eight 1.5-Gy fractions, twice daily on Day -8 till Day -5, along with 60 mg/kg high-dose etoposide on Day -4 and 100mg/kg high-dose cyclophosphamide on Day -2
  • Two patients refused ASCT and one failed mobilization
• Median patient age: 50 years
• Sex: 68% males
• Of the 28 T-NHL patients:
  • Had B-symptoms: 21 patients (75%)
  • Had stage IV disease at diagnosis: 14 patients (50%)
  • Were in the high-intermediate age-adjusted International Prognostic Index (IPI) risk group: 18 patients (64%)
  • Were in the high age-adjusted IPI risk group: 10 patients (36%)
• Histological T-NHL patient subtypes:
  • Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS): 11 patients
  • Angioimmunoblastic large cell lymphoma (AITL): 7 patients
  • Anaplastic large cell NHL (ALCL): 10 patients
    • Three of the ALCL patients were ALK positive

Key findings 

• Median follow-up (range): 7.8 (2.9−4) years
• Five-year progression-free survival (PFS; intention-to-treat [ITT] population):
  • ASCT group: 40% (95% CI, 16.5−8%)
  • Control group: 38% (95% CI, 14.1−8%)
  • Comparison: P = 0.56
• Five-year overall survival (OS; ITT):
  • ASCT group: 40% (95% CI, 16.5−8%)
  • Control group: 45% (95% CI, 17.7−0%)
  • Comparison: P = 0.98
• No outcome differences (PFS, OS) were observed based on IPI group, histology or disease stage subgroup analysis

Conclusions

• ASCT consolidation after first remission provided no added survival benefit to aggressive T-NHL patients
• There is a great unmet medical need for novel and improved induction therapies for T-NHL patients