R-CHOP-14 versus R-CHOP-14/CHASER for upfront autologous transplantation in diffuse large B-cell lymphoma: JCOG0908 study

Cancer Sci. 2020 Oct;111(10):3770-3779. doi: 10.1111/cas.14604. Epub 2020 Sep 11.

Abstract

The efficiency of upfront consolidation with high-dose chemotherapy/autologous stem-cell transplantation (HDCT/ASCT) for newly diagnosed high-risk diffuse large B-cell lymphoma (DLBCL) may be influenced by induction chemotherapy. To select better induction chemotherapy regimens for HDCT/ASCT, a randomized phase II study was conducted in high-risk DLBCL patients having an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3. As induction chemotherapy, 6 cycles of R-CHOP-14 (arm A) or 3 cycles of R-CHOP-14 followed by 3 cycles of CHASER (arm B) were planned, and patients who responded proceeded to HDCT with LEED and ASCT. The primary endpoint was 2-y progression-free survival (PFS), and the main secondary endpoints included overall survival, overall response rate, and adverse events (AEs). In total, 71 patients were enrolled. With a median follow-up of 40.3 mo, 2-y PFS in arms A and B were 68.6% (95% confidence interval [CI], 50.5%-81.2%) and 66.7% (95% CI: 48.8%-79.5%), respectively. Overall survival at 2 y in arms A and B was 74.3% (95% CI: 56.4%-85.7%) and 83.3% (95% CI: 66.6%-92.1%). Overall response rates were 82.9% in arm A and 69.4% in arm B. During induction chemotherapy, 45.7% and 75.0% of patients in arms A and B, respectively, had grade ≥ 3 non-hematologic toxicities. One patient in arm A and 6 in arm B discontinued induction chemotherapy due to AEs. In conclusion, R-CHOP-14 showed higher 2-y PFS and less toxicity compared with R-CHOP-14/CHASER in patients with high-risk DLBCL, suggesting the former to be a more promising induction regimen for further investigations (UMIN-CTR, UMIN000003823).

Keywords: JCOG-LSG; autologous stem-cell transplantation; diffuse large B-cell lymphoma; high-dose chemotherapy; induction chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Induction Chemotherapy / methods*
  • Lymphoma, Large B-Cell, Diffuse / therapy*
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Progression-Free Survival
  • Rituximab / administration & dosage
  • Rituximab / adverse effects
  • Transplantation, Autologous / adverse effects
  • Vincristine / administration & dosage
  • Vincristine / adverse effects
  • Young Adult

Substances

  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone