LENALIDOMIDE AT THE DOSE OF TWENTY-FIVE MG EVERY OTHER DAY IN PATIENTS AFFECTED BY MULTIPLE MYELOMA AND RENAL FAILURE : A REAL-LIFE EXPERIENCE
(Abstract release date: 05/18/17)
EHA Library. Cerchione C. 05/18/17; 182725; PB2011
Dr. Claudio Cerchione
Contributions
Contributions
Abstract
Abstract: PB2011
Type: Publication Only
Background
Lenalidomide, available as oral compound, is an IMiD with both antiproliferative and immunomodulatory activity which is largely used in the management of newly diagnosed, relapsed or refractory MM and as maintenance therapy after autologous stem-cell transplantation.
Due to its renal route of excretion, it is mandatory to adjust lenalidomide dose in patients with RI, guided by Creatinine Clearance (ClCr), in order to impede a systemic prolonged exposure that could boost myelosuppression.
With normal renal function, lenalidomide reaches its maximal plasma concentration after a median time of 0.6-1.5 h, and it is cleared by glomerular filtration and active tubular secretion in 3 to 4 hours. Serum half-life increases up to 9 hours if moderate/severe renal impairment is present (creatinine clearance <50 or <30 mL/min, respectively). In the latter cases a reduction of the daily dose is recommended. Dose adjustment based on RI severity decreases the daily amount of lenalidomide from 15 up to 5 mg (in patients undergoing dialysis); other studies include a schedule with 10 or 15 mg every other days.
However, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses.
Aims
In this report, we describe our retrospective experience on the administration of lenalidomide 25 mg every other day for patients with MM and RI.
Methods
From March 2014 to February 2016, 19 consecutive patients, 11 female and 8 male, with a median age of 63.3 years (range: 49-81) affected by advanced, resistant and progressive MM (median number of previous treatment lines: 3, range : 1-5, all including bortezomib) with concomitant renal failure not in dyalitic support (median calculated ClCr 36.4 ml/min, range : 18-66) were treated, after informed consent, with monthly 21-day courses of 25 mg lenalidomide every other day and dexamethasone (20-40 mg on days 1-8-15-22, every 28 days).
Results
Disappearance of urinary light chain and reduction of serum creatinine (complete response) were detected in 7 patients (36.8%); 3 patients (15.7%) had a very good partial response, 3 (15,7%) had a partial response, 4 of them (21.0%) were in stable disease, whereas 2 patients (10.5%) had signs of progressive disease. Overall response ratio was 68.2%. More than half of the patients (11/19, 57.8%) had a renal response (median calculated ClCr 51.5ml/min, range 20-148). Median progression free survival was 8 months (range 3-18 months). No patient experienced grade 4 myelotoxicity; four patients required red cell transfusions for grade 3 anemia. No SAE occurred during treatment.
Conclusion
Dose adjustment RI-related of Lenalidomide is recommended in most guidelines, but there is not a leading scheme with a proven effectiveness more than others.These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, in more than half of a small population of patients with advanced MM and renal impairment, with not negligible logistic and economic advantages. However, these results should be validated by controlled studies involving larger number of patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Renal failure, Myeloma, Imids
Abstract: PB2011
Type: Publication Only
Background
Lenalidomide, available as oral compound, is an IMiD with both antiproliferative and immunomodulatory activity which is largely used in the management of newly diagnosed, relapsed or refractory MM and as maintenance therapy after autologous stem-cell transplantation.
Due to its renal route of excretion, it is mandatory to adjust lenalidomide dose in patients with RI, guided by Creatinine Clearance (ClCr), in order to impede a systemic prolonged exposure that could boost myelosuppression.
With normal renal function, lenalidomide reaches its maximal plasma concentration after a median time of 0.6-1.5 h, and it is cleared by glomerular filtration and active tubular secretion in 3 to 4 hours. Serum half-life increases up to 9 hours if moderate/severe renal impairment is present (creatinine clearance <50 or <30 mL/min, respectively). In the latter cases a reduction of the daily dose is recommended. Dose adjustment based on RI severity decreases the daily amount of lenalidomide from 15 up to 5 mg (in patients undergoing dialysis); other studies include a schedule with 10 or 15 mg every other days.
However, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses.
Aims
In this report, we describe our retrospective experience on the administration of lenalidomide 25 mg every other day for patients with MM and RI.
Methods
From March 2014 to February 2016, 19 consecutive patients, 11 female and 8 male, with a median age of 63.3 years (range: 49-81) affected by advanced, resistant and progressive MM (median number of previous treatment lines: 3, range : 1-5, all including bortezomib) with concomitant renal failure not in dyalitic support (median calculated ClCr 36.4 ml/min, range : 18-66) were treated, after informed consent, with monthly 21-day courses of 25 mg lenalidomide every other day and dexamethasone (20-40 mg on days 1-8-15-22, every 28 days).
Results
Disappearance of urinary light chain and reduction of serum creatinine (complete response) were detected in 7 patients (36.8%); 3 patients (15.7%) had a very good partial response, 3 (15,7%) had a partial response, 4 of them (21.0%) were in stable disease, whereas 2 patients (10.5%) had signs of progressive disease. Overall response ratio was 68.2%. More than half of the patients (11/19, 57.8%) had a renal response (median calculated ClCr 51.5ml/min, range 20-148). Median progression free survival was 8 months (range 3-18 months). No patient experienced grade 4 myelotoxicity; four patients required red cell transfusions for grade 3 anemia. No SAE occurred during treatment.
Conclusion
Dose adjustment RI-related of Lenalidomide is recommended in most guidelines, but there is not a leading scheme with a proven effectiveness more than others.These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, in more than half of a small population of patients with advanced MM and renal impairment, with not negligible logistic and economic advantages. However, these results should be validated by controlled studies involving larger number of patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Renal failure, Myeloma, Imids
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