Abstract 3990

Poster Board III-926

Background

In 2005, the first ever Citizen Petition filed by a State Attorneys General, Attorney General Richard Blumenthal, requested that the FDA adopt 6 measures to improve VTE prophylaxis and patient safety of thalidomide (thal). While 4 recommendations were accepted, the FDA refused to mandate a Phase IV randomized, controlled trial designed to identify the best VTE prophylaxis stating that substantial data already existed, but no specific prophylaxis was identified. We review the progress of this safety concern pre- and post-FDA approval of thal in 2006, specifically for the use of multiple myeloma patients. Similar safety concerns apply to lenalidomide.

Methods

A literature search was performed from 2006 to 2009 through Pubmed and Ovid using the key words “thalidomide,” “lenalidomide,” “thrombosis,” and “multiple myeloma.” High dose thal was defined as higher than 200mg/d, low dose thal as 200mg/d or lower, and high dose dexamethasone (dex) as higher than 20mg/d and low dose dex as 20mg/d and lower.

Results

See table

ProphylaxisNoneASALMWHCoumadin
Result CategoryPreviousNewPreviousNewPreviousNewPreviousNew
Total Reports (n=7598)(n=1585)(n=2657)(n=178)(n=2373)(n=0)(n=470)(n=83)(n=252)
Dosage Low Thal/ Low Dex n/a 2%
\(3150\)
 		n/a n/a n/a 5%
\(238\)
 		n/a n/a 
Len+Dex 14%
\(86624\)
 		12%
\(106910\)
 		11%
\(1088\)
 		9%
\(2032165\)
 		n/a 0%
\(145\)
 		n/a n/a 
Low Thal/other agent 18%
\(949\)
 		4%
\(13319\)
 		n/a 8%
\(437\)
 		n/a 0%
\(053\)
 		n/a 1%
\(2202\)
 
Len/other agent n/a 2%
\(4222\)
 		7%
\(345\)
 		6%
\(354\)
 		n/a n/a n/a n/a 
High Thal/other agent 9%
\(37411\)
 		2%
\(6301\)
 		n/a n/a n/a n/a n/a n/a 
Low Thal/ High Dex 17%
\(35202\)
 		13%
\(82631\)
 		7%
\(345\)
 		8%
\(9117\)
 		n/a n/a n/a 14%
\(750\)
 
High Thal/ High Dex 7%
\(7106\)
 		12%
\(15124\)
 		n/a n/a n/a 29%
\(98334\)
 		6%
\(233\)
 		n/a 
High Thal/ Low Dex 11%
\(21193\)
 		n/a n/a n/a n/a n/a 16%
\(850\)
 		n/a 
ProphylaxisNoneASALMWHCoumadin
Result CategoryPreviousNewPreviousNewPreviousNewPreviousNew
Total Reports (n=7598)(n=1585)(n=2657)(n=178)(n=2373)(n=0)(n=470)(n=83)(n=252)
Dosage Low Thal/ Low Dex n/a 2%
\(3150\)
 		n/a n/a n/a 5%
\(238\)
 		n/a n/a 
Len+Dex 14%
\(86624\)
 		12%
\(106910\)
 		11%
\(1088\)
 		9%
\(2032165\)
 		n/a 0%
\(145\)
 		n/a n/a 
Low Thal/other agent 18%
\(949\)
 		4%
\(13319\)
 		n/a 8%
\(437\)
 		n/a 0%
\(053\)
 		n/a 1%
\(2202\)
 
Len/other agent n/a 2%
\(4222\)
 		7%
\(345\)
 		6%
\(354\)
 		n/a n/a n/a n/a 
High Thal/other agent 9%
\(37411\)
 		2%
\(6301\)
 		n/a n/a n/a n/a n/a n/a 
Low Thal/ High Dex 17%
\(35202\)
 		13%
\(82631\)
 		7%
\(345\)
 		8%
\(9117\)
 		n/a n/a n/a 14%
\(750\)
 
High Thal/ High Dex 7%
\(7106\)
 		12%
\(15124\)
 		n/a n/a n/a 29%
\(98334\)
 		6%
\(233\)
 		n/a 
High Thal/ Low Dex 11%
\(21193\)
 		n/a n/a n/a n/a n/a 16%
\(850\)
 		n/a 
View Large
Conclusion

Since 2006, we have found information on 2657 patients with no prophylaxis, 539 patients with thal/dex with prophylaxis, and 2210 patients with len/dex with prophylaxis. VTE rates remain high, except for the low dose thal and/or low dose dex group. Overall, optimal VTE prophylaxis remains an enigma. Current recommendations for VTE prophylaxis are not supported by empirical data. Against this backdrop, Blumenthal's team should consider resubmitting their safety request.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
patient safety, thalidomide, venous thromboembolism, lenalidomide, multiple myeloma, dexamethasone, low-molecular-weight heparin, thrombosis, warfarin

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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