title: Lenalidomide is effective and safe for the treatment of patients with relapsed multiple myeloma and very severe renal impairment.
abstract: Patients with multiple myeloma (MM) and severe renal impairment (SRI) have shorter survival than MM patients without renal failure. Although lenalidomide is a highly active drug, this immunomodulatory agent is frequently neglected in this context due to its predominant renal clearance and, consequently, an increased risk of toxicity. This risk might be overcome with the proper lenalidomide dose adjustment to renal function. This study evaluates the outcomes of 23 relapsed MM patients with SRI (baseline creatinine clearance (CrCl) <30 mL/min) treated with lenalidomide-dexamethasone (LenDex), including 56 % (13 patients) under hemodialysis. The median CrCl at start of LenDex was 19 mL/min; an overall response rate (partial response or better) of 56 % was obtained, with a median follow-up from start of LenDex of 52 months (8-79). The median time until maximal response was 4 months, and in 58 % (7/12), the response was longer than 2 years. Nine percent had renal improvement, but all the 13 patients on hemodialysis remained under treatment. LenDex was interrupted in three cases because of adverse events (infections and cutaneous events); 78 % of the patients were on thromboprophylaxis with aspirin. It is important to notice that, after initial dose adjustment of therapy, there should be a continuous process of dose adjustment, taking into account variations in renal function. Furthermore, lenalidomide dose adjustment should be made according to the individual tolerance, even with stable renal function. LenDex dose adjustment, according to these principles, does not negatively impact response and improves treatment tolerance. It has a clear potential to treat this group of patients and to induce long duration of responses [event-free survival (EFS) 20.5 m and overall survival (OS) 42.6 m].
authors.affiliation: Hemato-Oncology Unit, Champalimaud Centre for the Unknown, Lisboa, Portugal. cristina.joao@fundacaochampalimaud.pt.
authors.forename: Cristina
authors.initials: C
authors.lastname: João
authors.affiliation: Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Freitas
authors.affiliation: Oncology Department, Hospital Fernando Fonseca, EPE, Amadora, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomes
authors.affiliation: Hematology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Geraldes
authors.affiliation: Hematology Department, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Coelho
authors.affiliation: Hematology Department, Centro Hospitalar de Lisboa Norte, Lisbon, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Neves
authors.affiliation: Hemato-Oncology Unit, Champalimaud Centre for the Unknown, Lisboa, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Lúcio
authors.affiliation: Statistics and Clinical Research Unit, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Esteves
authors.affiliation: Hematology Department, Centro Hospitalar de Lisboa Norte, Lisbon, Portugal.
authors.forename: Graça V
authors.initials: GV
authors.lastname: Esteves
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D051437:Renal Insufficiency / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide
keywords: Hemodialysis; Lenalidomide; Multiple myeloma; Severe renal impairment