Subcutaneous Rituximab-MiniCHOP Compared With Subcutaneous Rituximab-MiniCHOP Plus Lenalidomide in Diffuse Large B-Cell Lymphoma for Patients Age 80 Years or Older

Abstract

PURPOSE: The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy—cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)—is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non–germinal center B-cell–like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2-miniCHOP. PATIENTS AND METHODS: Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS). RESULTS: A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2-miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, P = .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2-miniCHOP. CONCLUSION: The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population.

Cure rate in the elderly patients with diffuse large B cell lymphoma deteriorates after the age of 80—results from a single-center survey

“…Yet the 2-year OS rate (68%) of our elder age group (median age 83 years) seems to be plausible compared to a current multicentric, phase III, open-label, randomized trial conducted by the Lymphoma Study Association. In the study, 249 newly diagnosed patients aged at least 80 years (median age 83 years), treated with R-miniCHOP or R2-miniCHOP, showed a 2-year OS of approximately 66% [21]. As in other series, we found some negative impact of factors like lymphopenia or elevated LDH or extranodal manifestations in univariate analysis [22][23][24][25].…”

Clinical Outcomes, Treatment Toxicity, and Health Care Utilization in Older Adults with Aggressive Non-Hodgkin Lymphoma

“…Although patients' comorbidities have been shown to increase the risk of morbidity and mortality in patients receiving cancer therapy [33], the mechanisms by which hypoalbuminemia affects clinical outcomes remains unclear. Hypoalbuminemia may relate to nutritional status or disease biology as albumin is a prognostic factor for survival in DLBCL and is affected by proinflammatory mediators including interleukein-6, interleukin-1, and tumor necrosis factor [20,22,31,[34][35][36]. Future work should investigate the potential mechanisms underlying this relationship to identify novel biomarkers to identify those at the highest risk for treatment toxicity.…”

Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: a systematic review

“…Consistent with this finding, the use of R-miniCHOP is supported by prospective phase II data and the recently reported SENIOR trial (NCT02128061) where the standard R-miniCHOP arm and the experimental arm of R-miniCHOP plus lenalidomide showed a 2-year OS of 66% in patients $80 years. 21 To this end, R-miniCHOP now represents a standard of care for elderly ($80 years of age) or frail patients in many countries and is also accepted as a control arm when testing novel therapies in these populations (eg, R-miniCHOP vs R-mini-CHP and polatuzumab vedotin). However, these studies do not address whether full-dose R-CHOP is superior overall in those aged $80 years.…”