Note: This review is based upon a presentation at the 2012 American Society of Hematology (ASH) Annual Meeting, December 7-10 in Atlanta, Georgia.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report.
Anita Hill, Richard J Kelly, Austin G Kulasekararaj, Shreyans A Gandhi, Lindsay D Mitchell, Modupe Elebute, Stephen John Richards, Matthew Cullen, Louise M Arnold, Joanna Large, Alexandra Wood, Gemma L Brooksbank, Tracy Downing, Claire McKinley, Dena Cohen, Walter M Gregory, Judith C. W. Marsh, Ghulam J. Mufti, and Peter Hillmen
The authors from the United Kingdom were the first to treat patients with PNH with eculizumab, and were therefore able to report on long term results. This was also a very large group-- 153 patients, especially considering how rare the disorder is. They confirm that untreated patients with PNH have a very high rate of blood clotting (thrombosis) and that eculizumab reduces the chances of this complication by a factor of about 10. None of their patients died of clotting complications—which used to be the most common cause of death in patients with PNH. Two thirds of patients who had had blood transfusions did not need them at all after starting eculizumab. The remaining one third of patients had a significant reduction in the number of units of blood required. Life expectancy in patients on eculizumab was greatly improved compared with what has historically been seen in patients with PNH before the use eculizumab, though the survival rates were not yet quite equivalent to healthy individuals. There were three cases of a serious infection—meningococcemia-- but the researchers then started to put all of their patients on penicillin on a routine basis and there were no further cases of this seen. [In the United States, the use of penicillin is not yet routine in this situation, but patients on eculizumab are urged to come in to an emergency room immediately to get intravenous antibiotics at the first sign of any fever or any infection. They are also urged to carry oral antibiotics such as ciprofloxacin in the event that they do not quickly receive intravenous antibiotics for some reason.] Of note, none of the deaths were due to meningoccemia infection, probably because their patients were well educated about the risks and were quickly treated. Of the 9 deaths that did occur in this group of patients, 3 were related to serious forms of bone marrow failure such as progression to leukemia (which can occur rarely), 1 death was associated with bone marrow transplantation, and the remaining patients died of causes unrelated to PNH. This study shows that eculizumab retains its effectiveness in patients with PNH over many years. It strongly suggests that the drug is greatly improving life span in patients with PNH, probably by decreasing the risk of life-threatening blood clots.