Treatment decisions and outcome in very elderly patients with diffuse large B‐Cell lymphoma

We read with great interest the article by Williams et al that discussed the clinical presentation, treatment approach, and outcome of a large cohort of previously untreated elderly (aged 66-80 years) and very elderly patients (aged >80 years) diagnosed with diffuse large B-cell lymphoma (DLBCL). In their study, a total of 3479 elderly and 1156 very elderly patients with DLBCL who were recruited using the Surveillance, Epidemiology, and End Results registry were analysed retrospectively. As initially hypothesized, very elderly patients were less likely to receive treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or in association with rituximab (R-CHOP) and were more likely to receive the combination of cyclophosphamide, vincristine, and prednisone with or without rituximab or only observation; remarkably, treatment choice was influenced by both clinical and socioeconomic variables. Treatment with R-CHOP for >4 cycles was associated with improved overall survival (OS) for very elderly patients, and therefore the authors suggested this regimen should be considered as a feasible first-line treatment option. We greatly appreciate the effort to collect a large amount of data regarding very elderly patients with DLBCL because to the best of our knowledge this population is not represented in most clinical trials. We agree with the authors that a curative approach with R-CHOP should not be denied only because of advanced age and that a careful analysis of clinical, biological, and demographic characteristics should be made before treatment is selected. Despite the good quality of the study, we would like to make some observations. Because the Surveillance, Epidemiology, and End Results database does not include the receipt of oral medications and patients who died within 6 months of diagnosis were excluded, the analyzed cohort could not be representative of the real population. Moreover, only the CHOP regimen and the combination of cyclophosphamide, vincristine, and prednisone with or without rituximab and observation were examined, and we believe it could be interesting to include patients receiving other anthracycline-containing regimens (ACRs) or non– anthracycline-containing chemotherapy. Anthracyclines have been considered too toxic for very elderly patients, but their use has markedly improved survival and represents a milestone in the treatment of DLBCL. R-CHOP became the gold standard for elderly patients after the study by Coiffier et al was published, in which patients who were randomized to R-CHOP or CHOP therapy demonstrated an improved complete response rate, event-free survival, and OS, with manageable toxicity. These results were confirmed in the long-term follow-up analysis and in other large randomized studies, such as the US Intergroup Trial and the RICOVER-60 (Rituximab with CHOP over age 60 years) trial. In our opinion and as suggested by the International Society of Geriatric Oncology, alternative approaches are feasible without eliminating anthracyclines, such as dose reduction or the selection of a less toxic compound. In a prospective phase 2 study, Peyrade et al recruited 150 patients (with a median age 83 years) to receive attenuated immunochemotherapy (R-miniCHOP). The median progression-free survival and OS were 21 months and 29 months, respectively, with 2-year progression-free survival and OS rates of 47% and 59%, respectively; the treatment was found to be well tolerated and the most common adverse event was grade 3 to 4 neutropenia (CTCAEv.3). The weekly regimen of cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone with or without rituximab represents another interesting option allowing for the modulation of dose intensity and its adaptation to the patient’s condition. When substituted for doxorubicin, a nonpegylated liposomal doxorubicin demonstrated comparable efficacy with an acceptable toxicity profile in elderly patients in several phase 2 trials and a recently published review suggested its use in patients who are not eligible for conventional ACRs because of age and cardiac comorbidity or high cardiovascular risk. Finally, we underscore the importance of geriatric assessment. As recommended by the Italian Lymphoma Foundation, since 2009 our institution has used the Comprehensive Geriatric Assessment (CGA), the Basic Activities of Daily Living and Instrumental Activities of Daily Living, and comorbidities score according to the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). We have assessed >80 elderly patients to date and have classified each as fit, unfit, or frail. Fit patients are candidates for standard R-CHOP therapy whereas the optimal treatment for unfit and frail patients remains an unmet need. In particular, these patients could be treated, Correspondence