A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma

Abstract

The online version of this article has a Supplementary Appendix. BackgroundMantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma (NCT00516412). Design and MethodsEligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. ResultsThirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8-37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8-8.2) overall and 17.0 (6.4-23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. ConclusionsEverolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma.

Transplantation for mantle cell lymphoma: is it the right thing to do?

“…29 Everolimus has also shown single-agent efficacy in relapsed or refractory MCL, including patients who were refractory to bortezomib. 30 …”

Everolimus

“…Study NCT00516412 evaluated the activity of everolimus in MCL (Renner et al 2012). In thirty-five evaluable patients (median age 69), ORR was 20 % (95 % CI 8-37(, median PFS was 5.5 months (95 % CI 2.8-8.2).…”

Molecular pathogenesis of mantle cell lymphoma

“…Phase I/II studies are currently being performed to explore the best chemotherapy that may be added to temsirolimus and its potential role as maintenance therapy (87)(88)(89)(90)(91)(92). Other rapalogs, such as everolimus and deferolimus, and several PI3K inhibitors offer additional means to target the PI3K/AKT/mTOR pathway, although deferolimus has not showed clinical activity in relapsed MCL (93,94). The PI3K-δ inhibitor CAL101 has shown an overall response rate of 62% in relapsed and refractory MCL cases (95).…”