ABCL-237: Treatment of High-Grade Diffuse Large B-Cell Lymphoma (HG-DLBCL) of the Elderly with Lenalidomide, Rituximab, Cyclophosphamide, and Prednisone

The treatment of HG-DLBCL in elderly patients is challenging in contemporary oncology. Afflicted by cardio-vascular and other co-morbidities, elderly patients often cannot receive important agents such as anthracyclines. In addition, myelosuppression and severe constitutional effects limit their therapeutic possibilities. Thus, elderly patients often receive palliative treatments or none. IMiDs (immunomodulatory imide drugs) with thalidomide as the parent compound, have activity in the treatment of several inflammatory, autoimmune and neoplastic diseases. Their antiangiogenic and T-cell co-stimulatory functions has given them an important place in the treatment of hematologic neoplasms such as multiple myeloma and myelodysplastic syndromes. Lenalidomide, a second generation IMiD, has activity against DLBCL alone and in combination with rituximab, an anti-CD20 antibody. We have observed significant therapeutic activity of lenalidomide when combined with rituximab, cyclophosphamide, prednisone + vincristine in five elderly patients with high-grade DLBCL who were anthracycline-ineligible. Clinical Data: Five elderly patients, 87 years median age, and the diagnosis of high grade (Ki-67 >60%) DLBCL, clinical stage IV were treated with six cycles of rituximab 375mg/m2cyclophosphamide 750mg/m2and prednisone 100mg a day by mouth in combination with lenalidomide 10mg a day for 21 days of a 28 day cycle. Two of the five patients received vincristine at a dose not to exceed 2mg total dose. Four achieved a complete remission after 2 courses of treatment and one a partial remission. The median duration of response is 46 weeks and there has been no relapses. One died at 90 weeks of his established cardiomyopathy. Conclusion: The standard of care for HG-DLBCL is a combination of an anti-CD20 antibody with an anthracycline, doxorubicin together with cyclophosphamide, vincristine, and prednisone (R-CHOP). In these five elderly patients reported here, we have observed a dramatic impact of lenalidomide in HG-DLBCL when combined with rituximab, cyclophosphamide, prednisone + vincristine (ORR:100%). None of the five treated patients has relapsed. The regimen is well tolerated with no significant complications. The addition of cyclophosphamide and prednisone may greatly enhance the already known activity of lenalidomide alone or in combination with rituximab in DLBCL (ORR: 27 and 33% respectively) in anthracycline-ineligible patients.