Doubling rituximab in high‐risk patients with aggressive B‐cell lymphoma ‐results of the DENSE‐R‐MegaCHOEP trial

Abstract

Summary To further improve outcome in young high‐risk patients with diffuse large B‐cell lymphoma (DLBCL) the number of rituximab (R) infusions was doubled in combination with standard CHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone) chemotherapy. Seventy‐seven patients (aged 18–60 years) with an age‐adjusted International Prognostic Index of 2–3 received 12 × R (375 mg/m2) on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 99 together with eight cycles of CHOEP‐14. Results were retrospectively compared to those of patients receiving 6 × R and 8 × CHOEP‐14 in the standard arm of the randomized R‐MegaCHOEP trial. Two‐year overall survival (OS) was 82% [95% confidence interval (CI) 73%–92%]; 2‐year event‐free (EFS) and progression‐free survival (PFS) was 69% (95% CI 59–80%) and 76% (95% CI 66%‐–6%), respectively. Comparing 12 to six doses of R revealed no differences (univariate/multivariate) in EFS (at 2 years: 69% vs. 71%), PFS (76% vs. 75%) and OS (82% vs. 85%), with P = 0·766, P = 0·871 and P = 0·843, respectively. Doubling the number of R infusions concomitant to CHOEP did not improve treatment outcomes. Nonetheless, OS and PFS of young high‐risk patients who received only six infusions of R combined with CHOEP remain excellent and were confirmed in an independent cohort of patients.

SPARC-positive macrophages are the superior prognostic factor in the microenvironment of diffuse large B-cell lymphoma and independent of MYC rearrangement and double-/triple-hit status

“…The study was conducted within the Molecular Mechanisms in Malignant Lymphomas (MMML)-Demonstrators consortium and included patients affected by DLBCL and treated with R-CHOP-like regimens within the following clinical trials of the DSHNHL: MInT, 17 MegaCHOEP 18 and DENSE-R-MegaCHOEP, 19 including patients of age 60 years; and RICOVER-60, 20 RICOVER-noRTh, 21 DENSE-R-CHOP-14 22 and SMARTE-R-CHOP-14, 23 including patients of age >60 years. Treatment of all patients included cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and CHOP-like (additional etoposide, CHOEP) in combination with anti-CD20 (rituximab).…”

Anti-CD20 treatment for B-cell malignancies: current status and future directions

“…Of note, Phase 2 dose-escalation data in small numbers of patients suggested improved outcomes with higher dosages of rituximab [191], but this effect has not been reproduced or confirmed in larger trials [192,193,194]. Given that the recommended obinutuzumab dose and schedule ensures target saturation, increased efficacy observed with obinutuzumab is considered to be primarily due to mode of action and not the higher absolute dose given.…”

Central nervous system relapse in younger patients with diffuse large B-cell lymphoma: a LYSA and GLA/DSHNHL analysis

“…This study represents a joint analysis of the French Lymphoma Study Alliance (LYSA) and the German Lymphoma Alliance (GLA), formerly the Deutsche Studiengruppe Hochmaligne Non-Hodgkin Lymphome (DSHNHL). All patients in this analysis were treated on prospective clinical trials LNH03-1B, 20 LNH03-2B, 18 LNH03-3B, 21 LNH07-3B, 22 FLYER, 23 MInT, 24 UNFOLDER, 25 MegaCHOEP phase 2 26 and phase 3, 27 and DENSE-R-MegaCHOEP 28 launched by LYSA or GLA/DSHNHL.…”