Saturday, July 20, 2013

More on Halting the Lenalidomide Trial

Please read my immediate prior post on this trial first if you have not already to best understand the context of this post.

I heard from a respected investigator and my person physician in my ibrutinib trial, Dr. John Byrd, involved in the halted trial of Revlimid (lenalidomide) versus Leukeran (chlorambucil) in the elderly with CLL. 

He said the Kaplan Meir curves were narrowing. Deaths are now 28 versus 36, but still with more in the lenalidomide arm. He also said "The cause of death was interspersed among many different causes." And he reiterated "We are very excited about lenalidomide as an immune modulating agent at lower doses" suggesting that we might find use for it at a low dose by not only considering its potential to control the CLL, but also to rebuild our damaged immunity. 

This is completely consistent with the additional information presented below from the well balanced reporting of the Myeloma Beacon News.

I have pasted the last half of their article on the topic, the part that is most pertinent to CLL.

Lessons learned?
  1. Don't rush to judgement: Analyze all the data and don't generalize.
  2. Don't throw out the baby with the bathwater: Immune modulating drugs may be an important piece in solving the CLL puzzle.
  3. Expect the unexpected: Be prepared for something that you are are completely unprepared for.

Here is the last half  on the article. The full  article is available at this link but I jumped to the part that is more focused on CLL

As I said in my prior post, this is an evolving story.

Revlimid Leukemia Trial Halted – No Immediate Impact On Drug’s Use In Myeloma Expected

Published: Jul 19, 2013 4:52 pm

The decision to halt the ORIGIN study was based on an analysis conducted in March that showed CLL pa­tients treated with Revlimid had a 92 percent increased risk of dying compared to those treated with chlor­am­bucil.  Specifically, 16 percent of patients treated with Revlimid had died at that point, compared to 9 percent of patients treated with chlorambucil.

Click on image to view a larger version of it.
The results from the March analysis show that a dif­ference between the overall survival curves started to emerge around 6 months after the start of treatment (see graph on the right).
Celgene told The Beacon that the gap in the sur­viv­al curves has since grown smaller, but has not closed, and that the death rates are currently 18 percent for Revlimid and 13 percent for chlor­am­bucil.  These findings, however, have not yet been reviewed or confirmed by the FDA.
The FDA also has not yet released any information about what factors may have increased the risk of death among Revlimid-treated patients.  A spokes­per­son from the agency told The Beacon, “The FDA is working with [Celgene] to gather the infor­ma­tion needed to better understand the nature of the deaths.”
Greg Geissman, a spokesperson from Celgene, provided some additional information to The Beacon.  He explained that secondary cancers have not contributed to the increased risk of death among patients treated with Revlimid in this study.  He added that secondary cancers were balanced between the two treatment groups, both in terms of the rate of patients developing secondary cancers and the number of deaths at­trib­ut­able to secondary cancers.
Geissman also stated, “As we understand, a preliminary observation shows a greater imbalance in deaths in patients over the age of 80 who have co-morbidities [additional medical conditions]. Our analysis will now look to understand further some of these dynamics and how they may have contributed to the imbalance.”
In addition to analyzing the potential impact of age and co-morbidities on the survival imbalance, Celgene stated that the company will analyze differences in how the patients were cared for at the various centers involved in the study.  The company indicated that the results from these analyses will be presented at an upcoming medical meeting.
The Mayo Clinic’s Dr. Kumar also explained that “Other studies of Revlimid in CLL have shown that these patients can have unique side effects compared to myeloma patients, such as tumor flare.”
A tumor flare reaction is a temporary worsening of symptoms soon after treatment begins.  It can be a sign that treatment is working, but it requires that patients be monitored closely during the first few weeks of treat­ment.
“Given that the [survival] curves start separating out close to a year, it is unlikely that [tumor flare] explains the increased mortality, but it clearly would be one of the aspects to be examined in the future,” explained Dr. Kumar.
“As we know more details about the cause of deaths in the Revlimid arm in the CLL study,” added Dr. Kumar, “we should certainly evaluate if there are specific patients with myeloma where there might be a concern.”

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Anonymous Anonymous said...

With an enrollment of 450 patients in 153 sites, that amounts to about 3 patients per site with half not on Revlimid. Not exactly a number one would associate with good statistics per site.
Be well, TomD

July 27, 2013 at 7:40 AM  

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