Outcomes after first-line immunochemotherapy for primary mediastinal B-cell lymphoma: a LYSA study

Abstract

Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. Three hundred thirteen patients were enrolled and received rituximab (R) plus ACVBP (n=180) or CHOP delivered every 14 (R-CHOP14, n=76) or 21 days (R-CHOP21, n=57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%) and one (1.8%) patients in the R-ACVBP, R-CHOP14 and R-CHOP21 groups, respectively (p<0.001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8% and 76.6% (p=0.23) in the R-ACVBP, R-CHOP14 and R-CHOP21 groups, respectively. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14 and R-CHOP21 3-year progression-free survival (PFS) probabilities were 89.4% [95% confidence interval: 84.8-94.2%], 89.4% [82.7-96.6%] and 74.7% [64-87.1%] (p=0.018), respectively. A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower PFS (hazard ratio=2.18 [1.05-4.53]). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%, p<0.001) and mucositis (22.8% vs 3.9% vs 1.8%, p<0.001) were observed with R-ACVBP compared to R-CHOP regimens. PMBL patients treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.

Rituximab in addition to LMB-based chemotherapy regimen in children and adolescents with primary mediastinal large B-cell lymphoma: results of the French LMB2001 prospective study

“…Thus, CNS-directed therapy may be important in PMLBL and explains why we recommended since 2008 LMB B/C-modified regimen with rituximab, with some intrathecal therapy but also HD MTX and high-dose cytarabine (AraC). Recently, a real-world study from the French LYSA group also reinforces the benefit of dose intense immuno-chemotherapy regimens in PMLBL 17 : patients treated with R-ACVBP or R-CHOP14 achieved a better outcome than those treated with R-CHOP21 (progression-free survival of 89.4% vs . 74.7%).…”

Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B‐cell lymphoma in the rituximab era

“…The 2-year CI-CNSR of 1.47% (95% CI0.7%-2.8%) is the lowest incidence reported to date, compared to previously reported rates ranging from 2.3% to 3.8% in the rituximab era. 11,[17][18][19] However, all these estimations may in fact not be so discordant, considering the wide CI due to the low number of CNS events. More importantly, this rate of CNSR in PMLBCL is only minimally confounded by CNS prophylaxis, which was given in only 3% of the patients.…”

“…More intensive immunochemotherapy regimens, mainly R‐dose adjusted‐EPOCH (R‐da‐EPOCH), may provide even better disease control and nearly eliminate the need of radiotherapy (RT) 5–8 . R‐CHOP administered every 14 days (R‐CHOP‐14) has also been reported to improve disease control 9–11 . However, there are no data from randomized trials showing superiority of a more intensive regimen approach and the overall survival benefit is unclear.…”

“…[5][6][7][8] R-CHOP administered every 14 days (R-CHOP-14) has also been reported to improve disease control. [9][10][11] However, there are no data from randomized trials showing superiority of a more intensive regimen approach and the overall survival benefit is unclear.…”

“…14 CNSR had been consistently reported prior to the introduction of rituximab. 15 The incidence in the rituximab era has been estimated to 2.3%-3.8% in four patient series, 11,[17][18][19] thus remaining questionable whether it is reduced by the addition of rituximab. 18,19 Prognostic factors for CNSR in patients with PMLBCL have not been explored.…”