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ASH 2012: Dr. Siegel- Pomalidomide (POM) with Low-Dose Dexamethasone (LoDEX) in Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Impact of Renal Function on Patient Outcomes
David Siegel, MD, PhD
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, NJ
12.27.12
Program: Oral and Poster Abstracts
Session: 653. Myeloma - Therapy, excluding Transplantation: Poster III
Monday, December 10, 2012, 6:00 PM-8:00 PM
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)

David S. Siegel, MD, PhD1, Paul G. Richardson, MD2, Rachid Baz, MD3, Min Chen, PhD4*, Mohamed Zaki, MD5* and Kenneth C. Anderson, MD6

1John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ
2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
3Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
4Celgene Corporation, Summit, NJ
5Celgene Corp, Summit, NJ
6Dana-Farber Cancer Institute, Boston, MA

Background: One of the most common end-organ damage in pts with MM is renal insufficiency (RI). Patients (pts) presenting with severe RI generally have a poor outcome. However, those pts who correct their renal function achieve outcomes comparable to those of pts with normal renal function (Chanan Khan, Clin Cancer Res 2012;18:2145-63). POM is extensively metabolized and renally eliminated, with <5% eliminated as the parent drug. POM is approximately 30% protein-bound. The characteristics of POM suggest that exposure to parent drug would not be substantively affected by the degree of renal function. MM-002 is a multicenter phase 1/2 study randomizing heavily-pretreated RRMM pts to receive POM alone or POM+LoDEX (Richardson PG, et al. Blood 2011;118:abs 634). In this post hoc analysis of pts who received POM+LoDEX, safety data are analyzed according to the degree of renal function to determine whether renal function alters the safety profile of POM therapy.

Methods: Eligible pts with MM who had received ≥2 prior therapies were randomized to treatment with either POM+LoDEX (POM, 4 mg/day for days 1-21 of a 28-day cycle; LoDEX, 40 mg/week) or POM alone. Pts with baseline serum creatinine >3.0 mg/dL were excluded from the study. At progression, pts receiving POM alone could receive POM+LoDEX at investigator's discretion. Pts were retrospectively categorized into three groups based on calculated baseline creatinine clearance (CrCl) by the Cockcroft-Gault formula: CrCl >60 mL/min; CrCl 45-60 mL/min; CrCl <45 mL/min. Treatment-emergent adverse events (TEAEs) were defined as any AE occurring or worsening after first treatment with study medication and within 30 days after end of treatment. All pts received aspirin, 81 to 100 mg/day, or another form of thromboprophylaxis.

Results: A total of 113 pts received POM+LoDEX; the median age of these pts was 64 years (range 34-88). Median number of prior therapies was 5 (range 2-13). The majority of pts were male (62/113, 54.9%) and had an ECOG status score of 0 (32/113, 28.3%), or 1 (68/113, 60.2%). Seventy pts had CrCl >60 mL/min, 14 had CrCl 45-60 mL/min, and 26 had CrCl <45 mL/min. Only 5 pts had CrCl ≤30. The average daily dose of POM (4 mg) and the relative dose intensity (0.9) were similar across the three renal groups. Median time to first POM dose reduction by renal group was 49.5 days (d), 71.0 d, and 32.5 d respectively; treatment duration was 5.5 months (mos), 5.0 mos, and 3.4 mos, in pts with CrCl >60 mL/min, CrCl 45-60 mL/min, and CrCl <45 mL/min, respectively. Grade 3/4 TEAEs occurring in ≥10% of pts are presented in the Table. Grade 3/4 neutropenia was observed in 40% of pts with CrCl >60 mL/min, 21% of pts with CrCl 45-60 mL/min, and 54% of pts with CrCl <45 mL/min. Grade 3/4 anemia and thrombocytopenia were observed in 19%, 21%, 35% and 20%, 14%, and 15%, respectively for pts with CrCl >60 mL/min, CrCl 45-60 mL/min, and CrCl <45 mL/min. Frequently observed non-hematological grade 3/4 AEs included pneumonia and fatigue which was observed in 24%, 21%, 19% and 14%, 29%, and 8% of pts, respectively for pts with CrCl >60 mL/min, CrCl 45-60 mL/min, and CrCl <45 mL/min.

Conclusions: Adverse events observed with POM, given at 4 mg/day on days 1–21 of each 28-day cycle in combination with LoDEX, were generally comparable regardless to baseline renal function, however these data are confounded by low pt numbers. A prospective study (MM-008) investigating POM in MM pts with different degrees of renal impairment is ongoing.

Table:

 

 

CrCl >60 mL/min (n=70)

CrCl 45-60 mL/min

(n=14)

CrCl <45 mL/min

(n=26)

 
Grade 3/4 TEAEs occurring in >10% of pts, %

Neutropenia

40

21

54

Anemia

19

21

35

Thrombocytopenia

20

14

15

Leukopenia

10

14

4

Pneumonia

24

21

19

Urinary tract infection

6

7

19

Fatigue

14

29

8

Dyspnea

10

7

23

Back pain

10

7

12

Septic shock

0

14

0

Hyperkalemia

1

0

12

Other Grade 3/4 AEs of interest, %

Febrile neutropenia

1

0

4

Pulmonary embolism

1

0

4

Deep vein thrombosis

1

0

4

Rash

1

0

0

 


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