Treatment of the patient with diffuse large B-cell lymphoma with medical co-morbidities: Newer therapies needed

Recent improvements in the treatment of diffuse large B-cell lymphoma (DLBCL) have been achieved, thanks to the addition of the monoclonal antibody rituximab to chemotherapy [1 – 4]. In three different studies, rituximab-chemotherapy combinations improved the overall response, failure-free survival, and overall survival rates for patients younger than 60 years with good prognostic features by the Age-Adjusted International Prognostic Factors Index (IPI), and in older patients with any risk factors. However, these prospective randomized studies included only patients who had no other comorbid conditions. Although investigators performing these trials demonstrated improvement in the outcome for patients who receive treatment with curative intent, they did not provide information about how many patients actually did not qualify for such therapy and received only palliative treatment or no treatment at all for this potentially curable disease. In their study Hasselblom and colleagues identified 535 patients with DLBCL from the population-based Regional Lymphoma Registry of the Western Sweden Health Care Region who were enrolled from January 1995 to December 2000 [5]. Complete casebook data was available in 525 (98%) of these patients. Patients were separated into two groups: in one, patients received curative intent therapy, and in the other, patients received only palliative care. Those in the first group were treated with various anthracyclinecontaining combination chemotherapy regimens. If the disease relapsed, they received standard salvage regimens, with high-dose chemotherapy, and stem cell transplant was offered when indicated. After careful evaluation of their data, the authors concluded that male gender was an adverse prognostic factor. There was no significant difference in the number of male patients in the palliative care group (48%) compared with the curative intent group (55%). The authors found lower response and progression-free survival rates in male patients when compared with females. These results contradict those reported for aggressive lymphomas according to the International Non-Hodgkin’s Lymphoma Prognostic Factors Project Model where no differences were found in complete response (p1⁄4 0.849), relapse-free survival (p1⁄4 0.112), and overall survival rates (p1⁄4 0.455) for males compared with females [6]. The reasons for the differences between these two studies are unclear. Males may not tolerate therapy as well as females. Males may have more serious comorbidities. Also, males may have other adverse features not recognized because of the inherent problems associated with collection of data in this retrospective review. More importantly, curative intent therapy was offered to only 376 (70%) of all patients; 30% received only palliative care or no treatment at all, representing a very high number of patients who died with disease. Also, only 88% of the patients who received curative intent therapy actually completed their intended treatment. These two groups of patients, those who undergo little treatment and those who discontinue therapy early, represent a substantial number of patients who were considered undertreated. Incidence of undertreatment varies among different publications. In the Eindhoven Cancer Registry in the Netherlands, investigators found that only 89% of patients younger than 60 years and 77% of patients older than 60 received anthracyclinecontaining regimens [7]. In another study from the Comprehensive Cancer West registry in the