Pfreundschuh M, Trumper L, Osterborg A, et al. for the MabThera International
Trial (MInT) Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy
alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a
randomised controlled trial by the MabThera International Trial (MInT) Group.
Lancet Oncol 2006;7:379-91.
Treatment of newly diagnosed DLBCL with the R-CHOP regimen (rituximab plus cyclophosphamide,
doxorubicin, vincristine, and prednisone) is based upon French (GELA) and U.S.
Intergroup (ECOG 4494) trials demonstrating improved survival as compared with
CHOP alone in patients > 60 years of age. Although R-CHOP has been generally
adopted for treatment of younger patients as well, specific clinical study data
to support this approach has been lacking. Pfreundschuh et al. conducted a large
multinational randomized prospective trial in which patients age 16-60 with
low-risk DLBCL (age-adjusted IPI score of 0-1) received CHOP-like chemotherapy
(primarily CHOP or CHOP plus etoposide [CHOEP]), administered q21d with or without
concomitant rituximab. Radiation therapy 30-40 Gy was also administered to original
bulky sites of disease > 5 cm. As observed in elderly patients, the addition
of rituximab was associated with significantly improved event-free and overall
survival. Toxicities were similar in both groups. Somewhat surprisingly, prognostic
subgroups were identified even within this group selected as low-risk (Table).
Those with IPI 0 (i.e., limited stage), non-bulky disease had improved outcomes
versus those with bulky disease and/or IPI score of 1 (advanced stage, poor
performance status or high LDH).
DLBCL is the most common non-Hodgkin lymphoma subtype in the western world,
and is both clinically and biologically heterogeneous. This important trial
confirms and extends earlier studies and establishes R-CHOP as a current standard
for younger as well as older patients with DLBCL. There was no clear benefit
to those who received R-CHOEP as compared with R-CHOP, suggesting to these authors
that rituximab has a "chemo-equalizing" effect or that the more intensive
and toxic CHOEP regimen impaired immune effector mechanisms important to rituximab
response. The identification of a highly favorable subgroup of very low-risk
patients (IPI 0, non-bulky) suggests that they should be treated and studied
in future clinical trials separately from DLBCL patients with greater degrees
of risk. The addition of rituximab to CHOP has provided an important but incremental
advance in DLBCL, and it remains essential to continue to build upon this progress.
To this end, current clinical research in previously untreated DLBCL includes
dose-modulated chemo-immunotherapy (e.g., dose-adjusted R-EPOCH or dose-dense
R-CHOP), R-CHOP followed by radioimmunotherapy consolidation, and risk stratification
for early stem cell transplantation based upon clinical IPI score, phenotypic
or molecular markers, and PET response after 2-3 cycles of induction chemotherapy.
