title: Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 1b study from GELTAMO group.
abstract: Diffuse large B-cell lymphoma (DLBCL) patients failing rituximab-containing therapy have a poor outcome with the current salvage regimens. We conducted a phase 1b trial to determine the maximum tolerated dose (MTD) of lenalidomide in combination with R-ESHAP (rituximab, etoposide, cisplatin, cytarabine, methylprednisolone) (LR-ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were collected as a secondary objective. Subjects received 3 cycles of lenalidomide at escalating doses (5, 10 or 15 mg) given on days 1-14 of every 21-day cycle, in combination with R-ESHAP. Responding patients received BEAM (carmustine, etoposide, cytarabine, melphalan) followed by autologous stem-cell transplantation. Lenalidomide 10 mg/d was identified as the MTD because, in the 15 mg cohort, one patient experienced dose-limiting toxicity (grade 3 angioedema) and two patients had mobilization failure. A total of 19 patients (3, 12 and 4 in the 5, 10 and 15 mg cohorts, respectively) were evaluable. All toxicities occurring during LR-ESHAP cycles resolved appropriately and no grade 4-5 non-haematological toxicities were observed. The complete remission and overall response rates were 47·4% and 78·9%, respectively. With a median follow-up of 24·6 (17·4-38·2) months, the 2-year progression-free survival and overall survival were 44% and 63%, respectively. In conclusion, the LR-ESHAP regimen is feasible and yields encouraging outcomes.
authors: Department of Haematology, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors: Alejandro
authors: A
authors: Martín
authors: Department of Haematology, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors: Alba M
authors: AM
authors: Redondo
authors: Department of Haematology, Hospital Clinic, Barcelona, Spain.
authors: Iván
authors: I
authors: Dlouhy
authors: Department of Haematology, Hospital del Mar, Barcelona, Spain.
authors: Antonio
authors: A
authors: Salar
authors: Department of Haematology, Institut Català D'Oncologia Duran I Reynals, L'Hospitalet de Llobregat, Spain.
authors: Eva
authors: E
authors: González-Barca
authors: Department of Haematology, Hospital Universitario La Paz, Madrid, Spain.
authors: Miguel
authors: M
authors: Canales
authors: Department of Pathology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
authors: Santiago
authors: S
authors: Montes-Moreno
authors: Department of Haematology, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.|Centro de Investigación del Cáncer, IBMCC/CSIC-Universidad de Salamanca, Salamanca, Spain.
authors: Enrique M
authors: EM
authors: Ocio
authors: Department of Haematology, Hospital Clinic, Barcelona, Spain.
authors: Armando
authors: A
authors: López-Guillermo
authors: Department of Haematology, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors: Dolores
authors: D
authors: Caballero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003561:Cytarabine; D013792:Thalidomide; D005047:Etoposide; D000077269:Lenalidomide; D002945:Cisplatin; D011241:Prednisone
keywords: R-ESHAP; diffuse large B-cell lymphoma; lenalidomide; rituximab; salvage