Περίληψη:
Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to, 45 mL/min/1.73 m2); severe RI (cohort B; estimated glomerular filtration rate,, 30 mL/min/1.73 m2); and severe RI that requires hemodialysis (cohort C). Patients received pomalidomide 4 mg/d on days 1 to 21 and LoDEX 20 or 40 mg once per week in 28-day cycles. The primary end point was overall response rate. Results Of 81 enrolled patients (33, 34, and 14 patients in cohorts A, B, and C, respectively), 13 were still receiving treatment at data cutoff (January 28, 2017). Overall response rates were 39.4%, 32.4%, and 14.3%, with a median duration of response of 14.7 months, 4.6 months, and not estimable, respectively. Of importance, 100%, 79.4%, and 78.6% of patients, respectively, achieved disease control. With a median follow-up of 8.6 months, median overall survival was 16.4 months, 11.8 months, and 5.2 months, respectively. Complete renal responses were observed only in cohort A (18.2%), and no patients in cohort C became hemodialysis independent. Grade 3 and 4 hematologic treatment-emergent adverse events and pomalidomide discontinuations as a result of treatment-emergent adverse events occurred more frequently in cohort C. Pomalidomide pharmacokinetics were comparable among the three renal cohorts. Conclusion Pomalidomide 4 mg/d plus LoDEX is efficacious in patients with RRMM with moderate or severe RI, including those who had more advanced disease and required hemodialysis. The safety profile was acceptable among the three groups, and no new safety signals were observed. © 2018 by American Society of Clinical Oncology
Συγγραφείς:
Dimopoulos, M.
Weisel, K.
van de Donk, N.W.C.J.
Ramasamy, K.
Gamberi, B.
Streetly, M.
Offidani, M.
Bridoux, F.
de la Rubia, J.
Mateos, M.-V.
Ardizzoia, A.
Kueenburg, E.
Collins, S.
Di Micco, A.
Rosettani, B.
Li, Y.
Bacon, P.
Sonneveld, P.
Λέξεις-κλειδιά:
antibiotic agent; antivirus agent; bortezomib; cystatin C; dexamethasone; granulocyte colony stimulating factor; lenalidomide; pomalidomide; antineoplastic agent; dexamethasone; pomalidomide; thalidomide, adult; aged; anemia; cancer combination chemotherapy; cohort analysis; Conference Paper; disease severity; drug dose reduction; drug efficacy; drug half life; drug safety; drug withdrawal; estimated glomerular filtration rate; fatigue; febrile neutropenia; female; fever; follow up; hemodialysis; human; human tissue; hyperkalemia; hypocalcemia; infection; kidney biopsy; kidney disease; kidney failure; leukopenia; low drug dose; major clinical study; male; maximum plasma concentration; multicenter study; multiple cycle treatment; multiple myeloma; neutropenia; open study; overall survival; patient history of stem cell transplantation; peripheral edema; phase 2 clinical trial; plasma clearance; plasma concentration-time curve; pneumonia; priority journal; prospective study; relapse; thrombocytopenia; time to maximum plasma concentration; treatment duration; treatment response; clinical trial; complication; dose response; kidney failure; middle aged; multiple myeloma; pathophysiology; very elderly, Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Multiple Myeloma; Prospective Studies; Renal Dialysis; Renal Insufficiency; Thalidomide
