Everolimus as a single agent in refractory or relapsed Hodgkin's lymphoma: the Brazilian Named Patient Program Experience

Abstract

BackgroundDespite all the scientific progress that has been made on understanding the disease, prognosis for patients with relapsed and refractory Hodgkin's lymphoma remains poor and the treatment is palliative in the majority of the cases. Thus, the aim of this study was to present the results on the compassionate use of everolimus in a group of patients who were monitored at nine different centers in Brazil.MethodsA 10-mg oral dose of everolimus was given to each patient daily. Response time was evaluated from the beginning of medication use until loss of response, toxicity or medical decision to cease treatment.ResultsThirty-three patients were evaluated. The median age at the beginning of medication administration was 29 years. Patients had received a median of five prior therapies. Overall response rate was 45.4%, with 13 patients achieving partial response, two achieved clinical response, 14 remained with stable disease, two had disease progression, and two were not evaluated. Patients received a median of 14 cycles. Progression-free survival was nine months, and overall survival was estimated to be 36 months. Three patients used the medication for more than four years. The most frequently reported adverse events were thrombocytopenia and hypercholesterolemia. Three patients had pulmonary toxicity. Grade III and IV adverse events occurred in 39% of the patients.ConclusionEverolimus was found to provide a response in a group of patients with refractory or relapsed Hodgkin's lymphoma who had adequate tolerability to the drug.

Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies

“…190 Similar results were reported in a retrospective analysis of 33 heavily pretreated rr-cHL patients from Brazil. 191 The major toxicities of the drug include thrombocytopenia, anemia, fatigue, rash, and stomatitis, 190 while pneumonitis can be an issue in a minority of patients, being grade 3/4 very rarely. 191 Despite the single agent activity of everolimus, the combination everolimus-DHAP did not prove successful in the HD-R3i trial.…”

“…191 The major toxicities of the drug include thrombocytopenia, anemia, fatigue, rash, and stomatitis, 190 while pneumonitis can be an issue in a minority of patients, being grade 3/4 very rarely. 191 Despite the single agent activity of everolimus, the combination everolimus-DHAP did not prove successful in the HD-R3i trial. 192 Lenalidomide is an agent exerting immunomodulatory activity mainly through direct induction of apoptosis, antiangiogenesis, and activation of T-cell mediated immune response.…”

Treatment of Hodgkin Lymphoma – New and Developing Therapies and Their Potential Role in Standard of Care

“…117 A retrospective report from a named patient programme in Brazil reported a similar ORR of 45.4%, with CR reported in 6% of patients, and three patients adhering to therapy for over 4 years. 118 Further investigation may enable the identification of a subgroup of patients who respond particularly well to PI3K and mTOR inhibition, permitting optimisation of the use of these agents. 118,119 Immunomodulatory agents…”

“…118 Further investigation may enable the identification of a subgroup of patients who respond particularly well to PI3K and mTOR inhibition, permitting optimisation of the use of these agents. 118,119 Immunomodulatory agents…”

New agents in relapsed/refractory Hodgkin's lymphoma

“… 47 In the current issue of the Brazilian Journal of Hematology and Hemotherapy, a retrospective analysis of 33 relapsed/refractory HL patients who received everolimus in a compassionate use program in Brazil is reported. 48 Patients had received a median of five prior therapies and 88% had undergone an auto-SCT. The overall response rate was 45%; two (6%) patients achieved complete remission and 13 (39%) had a partial response.…”