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

• Published in: Haematologica (Roma) Vol. 98; no. 11; pp. 1732 - 1738
• Main Authors: Chiappella, Annalisa, Tucci, Alessandra, Castellino, Alessia, Pavone, Vincenzo, Baldi, Ileana, Carella, Angelo Michele, Orsucci, Lorella, Zanni, Manuela, Salvi, Flavia, Liberati, Anna Marina, Gaidano, Gianluca, Bottelli, Chiara, Rossini, Bernardo, Perticone, Sonia, De Masi, Pasqualina, Ladetto, Marco, Ciccone, Giovannino, Palumbo, Antonio, Rossi, Giuseppe, Vitolo, Umberto
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01-11-2013
• Subjects: Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antibodies, Monoclonal, Murine-Derived - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Chemotherapy-Induced Febrile Neutropenia - diagnosis; Chemotherapy-Induced Febrile Neutropenia - epidemiology; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Female; Humans; Italy - epidemiology; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - epidemiology; Male; Middle Aged; Prednisone - administration & dosage; Prednisone - adverse effects; Rituximab; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Treatment Outcome; Vincristine - administration & dosage; Vincristine - adverse effects; Italy
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2013.085134

Despite improvements in standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with untreated, diffuse large B-cell lymphoma, up to 40% of these patients relapse. Lenalidomide alone or in combination with rituximab has been shown to be active in relapsed/refractory aggressive lymphomas. In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab, cyclophosphamide, doxorubicin, vincristine and 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 and prednisone for a total of six courses. Seven cohorts of patients (n=3 in each cohort) 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 courses of treatment. The third dose-level of lenalidomide (15 mg/day) was selected as the maximum tolerated dose, with an estimated probability of dose-limiting toxicities 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 neurological (n=3), and grade 3 gastrointestinal (n=1). In this phase I study, the overall response rate was 90%, 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 NCT00907348.