Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi
- 28 June 2013
- journal article
- research article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 98 (11), 1732-1738
- https://doi.org/10.3324/haematol.2013.085134
Abstract
Despite improvements in standard therapy with rituximab-cyclophosphamide-doxorubicin- vincristine-prednisone scheme for patients with untreated, diffuse large-B-cell lymphoma up to 40% relapse. Lenalidomide alone or in combination with rituximab showed activity in relapsed/refractory aggressive lymphomas. In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab-cyclophosphamide-doxorubicin-vincristine- prednisone in untreated elderly (median age 68 years) patients with diffuse large-B-cell lymphoma. Four lenalidomide doses (5, 10, 15, and 20 mg/day on days 1-14) allocated using the continual reassessment method were planned to be administered for 14 days in combination with each course of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone for a total of six courses. Seven patient cohorts (n=3 each) were treated (total n=21) at 10, 20, 15, 15, 15, 10, and 10 mg of lenalidomide. Dose-limiting toxicities occurred in seven patients during the first three treatment courses. The third dose-level of lenalidomide (15 mg/day) was selected as the maximum tolerated dose, with an estimated dose-limiting toxicities probability of 0.345 (95% credibility interval 0.164-0.553). Grade 3-4 hematologic adverse events were: neutropenia in 28% of the courses, thrombocytopenia in 9%, and anemia in 3%. Non-hematologic toxicities were moderate: grade 4 increase of creatinine phosphokinase (n=1), grade 3 cardiac (n=2), grade 3 neurologic (n=3), and grade 3 gastrointestinal (n=1). In this phase I study, 90% of patients achieved an overall response with 81% achieving complete remission. This combination regimen appears safe in elderly patients with diffuse large-B-cell lymphoma and its efficacy will be assessed in the ongoing phase II trial. This trial was registered at www.clinicaltrials.gov as NCT00907348Keywords
This publication has 39 references indexed in Scilit:
- Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivoAmerican Journal of Hematology, 2009
- Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphomaBritish Journal of Haematology, 2009
- Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's LymphomaJournal of Clinical Oncology, 2008
- Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemiaBlood, 2008
- Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60)The Lancet Oncology, 2008
- Lenalidomide inhibits the malignant clone and up-regulates theSPARCgene mapping to the commonly deleted region in 5q− syndrome patientsProceedings of the National Academy of Sciences of the United States of America, 2007
- How I treat patients with diffuse large B-cell lymphomaBlood, 2007
- High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma – Results of a comprehensive meta-analysisCancer Treatment Reviews, 2007
- EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumoursEuropean Journal Of Cancer, 2006
- Rituximab-CHOP Versus CHOP Alone or With Maintenance Rituximab in Older Patients With Diffuse Large B-Cell LymphomaJournal of Clinical Oncology, 2006