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

Abstract

BACKGROUND:

Mantle 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 METHODS:

Eligible 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.

RESULTS:

Thirty-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.

CONCLUSIONS:

Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted.

• Authors: Christoph Renner, Pier Luigi Zinzani, Rémy Gressin, Dirk Klingbiel, Pierre-Yves Dietrich, Felicitas Hitz, Mario Bargetzi, Walter Mingrone, Giovanni Martinelli, Andreas Trojan, Krimo Bouabdallah, Andreas Lohri, Emmanuel Gyan, Christine Biaggi, Sergio Cogliatti, Francesco Bertoni, Michele Ghielmini, Peter Brauchli, Nicolas Ketterer, Swiss SAKK and French GOELAMS group from European Mantle Cell Lymphoma Network
• Journal: Haematologica (Haematologica) Vol. 97 Issue 7 Pg. 1085-91 (Jul 2012) ISSN: 1592-8721 [Electronic] Italy
• PMID: 22315486 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• Protein Kinase Inhibitors
• Everolimus
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Adult
• Aged
• Aged, 80 and over
• Disease-Free Survival
• Drug Administration Schedule
• Everolimus
• Female
• Humans
• Lymphoma, Mantle-Cell (drug therapy, mortality)
• Male
• Middle Aged
• Neoplasm Proteins (antagonists & inhibitors)
• Neoplasm Staging
• Prospective Studies
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Recurrence
• Remission Induction
• Sirolimus (administration & dosage, adverse effects, analogs & derivatives)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)