Topics Alert

Revlimid: A Breakthrough?!?

Date: May 23, 2024

I understand there is a great deal of interest expressed regarding Revlimid in the various chat rooms as the latest 'breakthrough' drug for CLL. As always, the devil is in the details and it helps to read the fine print in the press releases.

The efficacy of Revlimid reported in many of the lay press articles is in myeloid cancers and MDS, a very different set of cancers than our own beloved lymphoid cancer, CLL. Second, and the press articles do mention this, Revlimid is one of a long string of thalidomide derivatives that have been looked at, after the parent thalidomide showed benefit for myeloid cancers. The analogs are being developed in order to try and increase the benefit and reduce the toxicity associated with thalidomide.

Based on its encouraging performance in myeloid cancers, thalidomide has been tested in CLL as well (some of the work was done at Mayo Clinic, Rochester MN). Unfortunately thalidomide did not pan out for CLL — there was way too much toxicity, the most worrisome of which is peripheral nerve damage that may or may not be reversible — and not much by way of therapeutic efficacy. This is pretty old news. There was not much 'buzz' and very few papers on the use of thalidomide in CLL that made it into ASH 2024 book. I do not believe any rated the presentation of a full paper or even made it to the poster session. The real worry about use of thalidomide in CLL is something called 'thalidomide flares', where the lymphocyte count shoots up tremendously after the initiation of therapy. That and the peripheral neuropathy scared the hell out of patients, according to a couple of researchers I talked with. A recent phase-2 trial for CLL patients has not generated a great deal of optimism either.

The million dollar question is whether Revlimid has improved efficacy and reduced toxicity, compared to the parent drug thalidomide. The Roswell Park study recently announced at the ASCO described 18 relapsed CLL patients, three of whom got CR after a 28 day cycle of Revlimid (daily doses of 25mg for 21 days with a 7 day rest period). The authors said "Toxicity profile was predictable and manageable. The most common side effect was fatigue and rash in six patients. Flare reaction (tender swelling of lymph nodes) was noted in 73% of the patients while 2 patients were reported to have tumor lysis syndrome. Grade 3 / 4 toxicities included thrombocytopenia, anemia and neutropenia."

It is nice to know the toxicity was considered 'predictable and manageable' by the researchers; but chicken that I am, I worry about grade 3 and grade 4 thrombocytopenia, anemia and neutropenia. 3 CRs out of 18, (and I understand the cost of 2 of these 3 CRs included across-the-board cytopenia) along with high grade hematological toxicity, and 'flare' reactions in the majority (73%) of patients is a pretty steep price to pay, if it is my body that is at the wrong end of the sharp injection needle.

It is very hard to compare these early stage test results of Revlimid with more mature study results with drugs such as Campath. As things stand right now, I am hard pressed to find the advantage of Revlimid over Campath for refractory CLL patients. The recent study of Campath even in the case of fludarabine refractory CLL patients had better stats than this. You can read the details in the review Good News for the Tough Cases. But I will be the first to admit, the comparison is not really kosher. These are very early results with Revlimid. We need to be patient until larger and more mature clinical trial results are available before we can declare Revlimid a 'breakthrough' drug for CLL patients.

This is the whole point of running well conducted clinical trials. They sort out the details, distinguish the really important drugs from the short-term wonders. Without clinical trials and without generous patients willing to risk their necks in such trials, we will never get new and better drugs. Having said that, it bothers me when the lay press gets into the act with gushing reports of 'breakthrough' drugs, based on early stage results and an even more skimpy understanding of the details. CLL is an indolent disease. There are many ways in which we can jump the gun and make things worse than they were to begin with, if the toxicity of the therapy is not matched and surpassed by the long term benefits of the drugs used. A certain amount of skepticism is a good thing, when you buy into a new and unproven drug.

Be well,

Chaya
_____

———

Disclaimer: The content of this website is intended for information only and is NOT meant to be medical advice. Please be sure to consult and follow the advice of your doctors on all medical matters.

Copyright Notice:

Copyright © 2024-2007 CLL Topics, Inc. All Rights Reserved.

All materials contained on this site are protected by United States copyright law and may not be reproduced, distributed, transmitted, displayed, published or broadcast without the prior written permission of CLL Topics, Inc. You may not alter or remove any trademark, copyright or other notice from copies of the content.

However, you may download and print material from CLLTopics.org exclusively for your personal, noncommercial use.

———

Topics Alert