Background R-CHOP can cure approximately 75% of patients with primary
mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have
not been sufficiently evaluated yet. R-da- EPOCH is potentially more
effective but also more toxic than R-CHOP. Reliable prognostic
classification is needed to guide treatment decisions.
Materials and Methods We analyzed the impact of clinical prognostic
factors on the outcome of 332 PMLBCL patients <= 65 years treated with
R-CHOP +/- radiotherapy in a multicenter setting in Greece and Cyprus.
Results With a median follow-up of 69 months, 5-year freedom from
progression (FFP) was 78% and 5-year lymphoma specific survival (LSS)
was 89%. On multivariate analysis, extranodal involvement (E/IV) and
lactate dehydrogenase (LDH) >= 2 times upper limit of normal (model A)
were significantly associated with FFP; E/IV and bulky disease (model B)
were associated with LSS. Both models performed better than the
International Prognostic Index (IPI) and the age-adjusted IPI by
Harrel’s C rank parameter and Akaike information criterion. Both models
A and B defined high-risk subgroups (13%-27% of patients [pts]) with
approximately 19%-23% lymphoma-related mortality. They also defined
subgroups composing approximately one-fourth or one-half of the
patients, with 11% risk of failure and only 1% or 4% 5-year
lymphoma-related mortality.
Conclusion The combination of E/IV with either bulky disease or LDH >= 2
times upper limit of normal defined high-risk but not very-high-risk
subgroups. More importantly, their absence defined subgroups comprising
approximately one-fourth or one-half of the pts, with 11% risk of
failure and minimal lymphoma-related mortality, who may not need more
intensive treatment such as R-da-EPOCH.
Implications for Practice By analyzing the impact of baseline clinical
characteristics on outcomes of a large cohort of patients with primary
mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with
or without radiotherapy, we developed novel prognostic indices which can
aid in deciding which patients can be adequately treated with R-CHOP and
do not need more intensive regimens such as R-da-EPOCH. The new indices
consist of objectively determined characteristics (extranodal disease or
stage IV, bulky disease, and markedly elevated serum lactate
dehydrogenase), which are readily available from standard initial
staging procedures and offer better discrimination compared with
established risk scores (International Prognostic Index [IPI] and
age-adjusted IPI)