title: Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma.
abstract: For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m2IV, days 1-2 and R 375 mg/m2IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2Pneumocystis cariniipneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.
authors.affiliation: Department of Oncology, Skåne University Hospital, Lund, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Albertsson-Lindblad
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Arne
authors.identifier: 0000-0003-2699-3357
authors.initials: A
authors.lastname: Kolstad
authors.affiliation: Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Laurell
authors.affiliation: Department of Hematology, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Räty
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbæk
authors.affiliation: Department of Oncology, Skåne University Hospital, Lund, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Sundberg
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lone Bredo
authors.initials: LB
authors.lastname: Pedersen
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiær
authors.affiliation: Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Karjalainen-Lindsberg
authors.affiliation: Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; and.
authors.forename: Christer
authors.identifier: 0000-0002-8160-5647
authors.initials: C
authors.lastname: Sundström
authors.affiliation: Department of Pathology/Cytology, Lund University Hospital, Lund, Sweden.
authors.forename: Mats
authors.identifier: 0000-0003-2342-1679
authors.initials: M
authors.lastname: Ehinger
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Department of Oncology, Skåne University Hospital, Lund, Sweden.
authors.forename: Mats
authors.identifier: 0000-0003-4509-6707
authors.initials: M
authors.lastname: Jerkeman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D020522:Lymphoma, Mantle-Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000069283:Rituximab; D013792:Thalidomide; D000069461:Bendamustine Hydrochloride; D000077269:Lenalidomide