Santhosh Sadashiv

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.

Rituximab-Induced Acute Severe Thrombocytopenia: A Case Series in Patients With Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a B-cell lymphoma that accounts for 3% to 10% of the non-Hodgkin forms of lymphoma. MCL almost universally expresses CD 20, the target of the monoclonal antibody rituximab. Therapy frequently combines rituximab with other chemotherapeutic agents. Administration of rituximab intravenously is well tolerated but frequently causes infusion reactions. Hematologic toxicity is seen less commonly but is well defined. Neutropenia, anemia, and thrombocytopenia have been described and often occur in the 10to 14-day window after rituximab infusion, similar to that seen with conventional chemotherapeutic agents. Isolated cases of acute severe thrombocytopenia after rituximab infusion for treatment of MCL have been reported, but this toxic event is uncommon. We identified 5 cases of acute severe thrombocytopenia occurring within 3 days of the administration of rituximab, suggesting that this toxic event might occur more frequently than previously recognized. Our series shows that acute severe thrombocytopenia is not always associated with infusion reactions, suggesting that the pathogenesis of these two toxic events might be different. Acute severe thrombocytopenia is reported more commonly in MCL than in other lymphomas treated with similar regimens. Four of the 5 patients received platelet transfusion. Subsequently, all the patients exhibited rapid recovery from thrombocytopenia without bleeding complications. Because acute severe thrombocytopenia appears to be transient, unpredictable, and not associated with bleeding complications, we would caution against the cessation or dose reduction of rituximab when treating MCL.

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.

Case series of unique adverse events related to the use of ibrutinib in patients with B-cell malignancies—A single institution experience and a review of literature

Background Ibrutinib, a Bruton’s tyrosine kinase inhibitor has reformed the treatment of various B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. Although generally well tolerated, here we describe our institutional experience of unique adverse effects encountered with the use of ibrutinib in patients with B-cell lymphomas. Methods This is a retrospective observational study done at a tertiary care facility, to evaluate adverse events in patients with B-cell malignancies on treatment with ibrutinib between 2014 and 2018. Further details including type of malignancy, cytogenetics, interventions for treatment of the side effect, and outcomes were obtained through electronic health record. Case series We found 10 patients with unique adverse events related to ibrutinib. Among those, six had chronic lymphocytic leukemia, two had Waldenstrom’s macroglobulinemia, and two had mantle cell lymphoma. The events included palindromic rheumatoid arthritis, diffuse spongiotic dermatitis, bullous pemphigoid, recurrent hemorrhagic stroke, peripheral neuropathy, recurrent paronychia, intramedullary fibrosis, recurrent joint pains, pulmonary aspergillosis, dyspnea with exacerbation of atrial fibrillation, and resolution of autoimmune hemolytic anemia. Conclusion Our case series illustrates the wide variety of unique events recognized in patients treated with ibrutinib, some of which required cessation and most had dose reduction of the treatment. Thus, stressing the importance of early identification and intervention for the events to avoid worsening of toxicity and inability to continue treatment in such patients.