Abstract 3963

Background:

Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with relapsed multiple myeloma (MM). Between November 2007 and November 2010, we opened 5 sequential phase 2 trials using the pomalidomide at differing doses with weekly dexamethasone (Pom/dex) regimen to study the efficacy of this regimen.

Methods:

The five cohorts consisted of: Cohort 1 (N=60): relapsed MM with 1–3 prior regimens, 2 mg dose; Cohort 2 (N=34): lenalidomide refractory, 2 mg dose; Cohort 3 (N=35): bortezomib/lenalidomide refractory, 2 mg dose; Cohort 4 (N=35): bortezomib/lenalidomide refractory, 4 mg dose; and Cohort 5 (N=60) lenalidomide refractory, 1–3 prior regimens, 4 mg dose. Pomalidomide was given orally 2 mg daily or 4mg daily on days 1–28 of a 28-day cycle with oral dexamethasone given 40 mg daily on days 1, 8, 15 and 22. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily for DVT prophylaxis or full dose anticoagulation.

Results:

A total of 225 patients were enrolled across all 5 cohorts. One patient was ineligible and excluded from analysis. The median age was 63 years (32.0–88.0). The median time since diagnosis was 53 months. Forty percent had high-risk molecular markers. Eighty-nine percent had received previous IMIDs including thalidomide (53%) and lenalidomide (81%). Sixty-two percent had previous bortezomib and 73% had prior transplant. The median follow-up is 12.6 months, but varies from 9.4 months for the most recent cohort to 30 months for the first cohort. Sixty-nine percent are alive and 30% remain progression free. Toxicities ≥ grade 3 are shown in table 1 and patient outcomes are shown in Table 2.

Table 1.

Toxicity, grade 3 or higher

2mg2mg2mg4mg4mg
1–3 RegLen RefractoryBortz/Len RefractoryBortz/Len RefractoryLen Refractory 1–3 Reg
N=60N=34N=35N=35N=60
Hematologic      
Neutropenia 48% 41% 51% 66% 48% 
Anemia 10% 18% 26% 26% 13% 
Platelets 12% 12% 31% 31% 8% 
Non Hematologic      
Fatigue 25% 18% 9% 9% 8% 
Pneumonia 18% 20% 29% 3% 15% 
Neuropathy 2% 0 0 3% 2% 
2mg2mg2mg4mg4mg
1–3 RegLen RefractoryBortz/Len RefractoryBortz/Len RefractoryLen Refractory 1–3 Reg
N=60N=34N=35N=35N=60
Hematologic      
Neutropenia 48% 41% 51% 66% 48% 
Anemia 10% 18% 26% 26% 13% 
Platelets 12% 12% 31% 31% 8% 
Non Hematologic      
Fatigue 25% 18% 9% 9% 8% 
Pneumonia 18% 20% 29% 3% 15% 
Neuropathy 2% 0 0 3% 2% 

Len: lenalidomide; Bortz:bortezomib;

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Table 2.

Patient Outcomes

2mg2mg2mg4mg4mg
1–3 RegLen RefractoryBortz/Len RefractoryBortz/Len RefractoryLen Refractory 1–3 Reg
N=60N=34N=35N=35N=60
All cycle Confirmed Response Rate (≥PR) 65% 32% 26% 29% 37% 
Median time to response 1.7 mo 2.0 mo 1 mo 1.8 mo 1.1 mo 
Duration of response1 21 mo 9 mo 16 mo 3 mo NA 
Overall Survival1 40 mo 27 mo 17 mo 9 mo NA 
6 Months OS 95% 85% 76% 67% 93% 
Progression Free Survival1 13 mo 4.7 mo 6.5 mo 3.3 mo 7.9 mo 
6 Months PFS 73% 44% 56% 37% 63% 
2mg2mg2mg4mg4mg
1–3 RegLen RefractoryBortz/Len RefractoryBortz/Len RefractoryLen Refractory 1–3 Reg
N=60N=34N=35N=35N=60
All cycle Confirmed Response Rate (≥PR) 65% 32% 26% 29% 37% 
Median time to response 1.7 mo 2.0 mo 1 mo 1.8 mo 1.1 mo 
Duration of response1 21 mo 9 mo 16 mo 3 mo NA 
Overall Survival1 40 mo 27 mo 17 mo 9 mo NA 
6 Months OS 95% 85% 76% 67% 93% 
Progression Free Survival1 13 mo 4.7 mo 6.5 mo 3.3 mo 7.9 mo 
6 Months PFS 73% 44% 56% 37% 63% 

mo: month; NA: not attained; 1) Kaplan Meier

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Conclusions:

Pom/dex is remarkably active and well tolerated even in heavily pretreated patients. Responses are durable. Response rates and toxicity are similar between the 2 mg and 4 mg doses.

Disclosures:

Lacy:Celgene: Research Funding. Fonseca:Consulting:Genzyme, Medtronic, BMS, Amgen, Otsuka, Celgene, Intellikine, Lilly Research Support: Cylene, Onyz, Celgene: Consultancy, Research Funding.

Topics:
dexamethasone, multiple myeloma, pomalidomide, lenalidomide, bortezomib, toxic effect, anemia, anticoagulation, aspirin, biological markers

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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