Fast track — ArticlesAttenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial
Introduction
Diffuse large B-cell lymphoma is the most common lymphoid malignancy worldwide.1 Its incidence steadily increases with age and about 40% of cases occur in patients aged over 70 years.1, 2 However, few prospective data are available on the outcome of patients aged over 80 years. Retrospective analyses have shown that the outcome of elderly patients is worse than that of younger patients but that some elderly patients do have a complete response to treatment and long-term survival.3, 4, 5, 6
Whether diffuse large B-cell lymphomas in the elderly differ intrinsically from those in younger patients is not clear. Although there is no specific histological characteristic or genetic abnormality of diffuse large B-cell lymphoma in elderly people, the distribution of gene-expression profile subtypes with distinct prognosis might differ with age.7 Lymphoma in elderly patients is not substantially less responsive to treatment than in younger patients, and the main reason for the poor outcome of very old patients is their decreased ability to tolerate treatment.8 Impaired bone-marrow function, altered drug metabolism, and presence of comorbid diseases can increase the number of treatment-related complications. Several attempts to decrease doses of the standard chemotherapy regimen CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) or to substitute less toxic drugs in the combination have decreased toxicity but did not improve survival.9, 10, 11
Over the past 10 years, since the introduction of the chimeric anti-CD20 monoclonal antibody rituximab as the standard treatment, the treatment outcome of patients with diffuse large B-cell lymphoma has changed dramatically. In a randomised open-label trial by the Groupe d'Etudes des Lymphomes de l'Adulte (GELA) in patients aged 60–80 years, the association of CHOP and rituximab was significantly superior to CHOP alone in terms of complete response rate and survival, without a clinically significant increase in toxicity.12, 13, 14 This study did not include patients aged over 80 years but did show a similar benefit for patients aged 60–70 years, 71–75 years, and 76–80 years.13 These results have since been replicated by two randomised trials in a similar patient population,15, 16 but no prospective study of this association has been done for patients aged over 80 years.
After the results of a small retrospective study6 that showed that rituximab could help maintain efficacy of a dose-reduced regimen in patients over 80 years old who had non-Hodgkin lymphoma, we decided to assess the efficacy and safety of the combination of a standard dose of rituximab and an attenuated dose of chemotherapy in this patient population.
Section snippets
Study design and patients
We did a prospective, multicentre, single-arm study of a low-dose CHOP chemotherapy regimen and rituximab (R-miniCHOP) in elderly patients with diffuse large B-cell lymphoma. GELA ran the study in 38 centres in France and Belgium. Patients were eligible if they were aged over 80 years and had untreated histologically proven CD20+ diffuse large B-cell lymphoma according to WHO classification.17 Inclusion criteria were Ann Arbor stage I bulky to stage IV disease; age-adjusted international
Results
From Jan 9, 2006, to Jan 23, 2009, 150 patients (51 men and 99 women) were enrolled in the study, 149 of whom received treatment and were included in the intention-to-treat analyses (figure 1). The imbalance between men and women is consistent with the demographic distribution of elderly men and women. Table 1 shows patient characteristics. All patients had a performance status score lower than or equal to 2, according to the protocol criteria. 75% of patients had an Ann Arbor stage III or IV,
Discussion
In this phase 2 study of patients over 80 years old who have diffuse large B-cell lymphoma treated with an attenuated immunochemotherapy, we recorded a 29-month median overall survival and a 62% complete response and unconfirmed complete response rate. After the third cycle, the overall response rate was the same as at the end of treatment but the complete or unconfirmed complete response rate was lower than at the end of treatment, suggesting that some patients in partial remission achieved
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