Cyrus Khan

Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia

Acute myeloid leukemia (AML) patients aged ≥60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m2/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20–30%. Here, we report the results of a prospective, phase 2, open‐label study that evaluated the tolerability and efficacy of a 5‐day regimen of single‐agent subcutaneous azacitidine 100 mg/m2/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13–724 days). Grade 3–4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection‐site skin reactions and fatigue (Grades 1–2), occurred in 73% (n = 11) of patients. No treatment‐related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m2/day for 5 days every 28 days is a feasible, well‐tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML.

Frontline treatment of diffuse large B-cell lymphoma in elderly: a systematic review of clinical trials in post-rituximab era

Abstract Treatment of diffuse large B cell lymphoma (DLBCL) remains challenging in elderly population and systematic reviews are lacking in this area. Medline and Cochrane Register of Controlled Trials in addition to conference proceedings were searched for therapeutic clinical trials on frontline treatment of DLBCL in adults ≥60 in post-rituximab era. Forty-one out of 713 reviewed papers met our inclusion criteria. Six cycles of rituximab, cyclophosphamide, vincristine, prednisone (R-CHOP) administered every 21 d remain the standard treatment for fit elderly, with no role for maintenance rituximab. For individuals ≥80, the strongest evidence favors rituximab/ofatumumab-miniCHOP. Numerous alternative approaches including the use of liposomal anthracyclines, dose and regimen adjustment to frailty/comorbidity score, brief duration regimens, and consolidative radioimmunotherapy have produced promising outcomes and could be considered for R-CHOP inappropriate elderly. Phase III randomized trials studying the efficacy of liposomal vincristine, extended-exposure rituximab, and lenalidomide plus R-CHOP are ongoing.