[Mark11]

Meta-analysis of maintenance therapy with IMiDs

by Mark11 on Fri Nov 20, 2015 3:40 pm

I know the topic of maintenance is one of the most discussed here. Note one of the co-authors of this study is one of my "favorites".

Results:

Eighteen phase 3 RCTs enrolling 7730 patients were included. IMiD-based maintenance therapy statistically significantly prolonged progression-free survival (PFS; hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.57 to 0.67, P < .001) but failed to improve overall survival (OS; HR = 0.93, 95% CI = 0.85 to 1.01, P = .082). Stratified analyses demonstrated that both thalidomide and lenalidomide provided PFS but not OS benefit in transplantation as well as nontransplantation settings. IMiD-based maintenance therapy in multiple myeloma led to a higher risk of grade 3-4 thromboembolism (risk ratio = 2.52, 95% CI = 1.41 to 4.52, P = .002). Thalidomide maintenance therapy increased the risk of peripheral neuropathy; lenalidomide maintenance therapy increased the risks of myelosuppression and second primary hematological malignancies.

Conclusions:

Thalidomide- or lenalidomide-based maintenance therapy improves PFS but not OS in multiple myeloma and increases risks of grade 3-4 adverse events, including thromboembolism, peripheral neuropathy, neutropenia, and infection."

Source: Y Wang et al, "Maintenance Therapy With Immunomodulatory Drugs in Multiple Myeloma: A Meta-Analysis and Systematic Review," Journal of the National Cancer Institute, Nov 18, 2015 (abstract)

[Multibilly]

Re: Meta-analysis of maintenance therapy with IMiDs

by Multibilly on Fri Nov 20, 2015 4:20 pm

This is the full article on the subject:

http://jnci.oxfordjournals.org/content/108/3/djv342.full

[Mike F]

Re: Meta-analysis of maintenance therapy with IMiDs

by Mike F on Fri Nov 20, 2015 8:29 pm

I saw that today as well. It will be interesting to see how this affects the currently common (at least as far as I can tell) practice of long-term Revlimid maintenance.

[RadiantTiger]

Re: Meta-analysis of maintenance therapy with IMiDs

by RadiantTiger on Fri Nov 20, 2015 9:00 pm

Thanks for posting Mark.

I am a month post-transplant (ASCT) and am basically dreading the thought of going on long-term Revlimid maintenance. My doctors are in the 'Revlimid-maintenance-forever camp'. Will definitely look at 'plan B' for myself. After a year of almost continuous drugs, I desperately need a break!

RT
Peace to all those suffering from the symptoms of myeloma and it's pharmaceutical interventions

[JPC]

Re: Meta-analysis of maintenance therapy with IMiDs

by JPC on Sat Nov 21, 2015 11:08 am

Good morning:

I would like to add a couple of thoughts to this topic on the meta-analysis with respect to "maintenance therapy". I read the abstract, but the whole article link did not work for me. So these are general comments on retrospective studies.

To make my main point clearly, let me state that a meta-analysis or retrospective study is not a REAL study. It is a rehash of older studies that are combined together. It has no original data. In the hierarchy of studies, in is at the low end of rigor. It is like a back of the envelope estimation compared to the more rigorous studies.

There were several new drugs approved this year. Regulatory agencies would never approve a new drug or a new procedure based on a retrospective study or meta analysis. Approvals would need to be based on the results of large multi-arm, multi-center randomized phase 3 studies, which are the most rigorous type of study. One such study on maintenance, in fact, was the recent update to the CALGB study that disagreed with the results of this retrospective meta-analysis, with respect to overall survival on maintenance.

So you could look at this newly published study, and say, well, this balances out the CALGB study, and we are back to square 1 at maintenance. So in that regard, I think the original post in this thread could be misinterpreted. When you read an abstract for a meta-analysis, it has confidence intervals and statistics that look like other studies, so if you read it quickly, you could leap to the conclusion that a meta-analysis is equal to a rigorous phase 3 study that has been recently published, but it is not.

I will take back my original comment at the start of this post that a meta-analysis is not a REAL study. I was just making a point Properly interpreted and explained, it is valid and has its place, and I am sure has proved very useful in some settings. However, very likely, that data is very old. By the very nature of studies, and the fast advance of the new treatment options coming out, the newest of studies are somewhat obsolete on the day that they were just published. For a meta-analysis of older studies, with no control between studies and inherent biases that are unavoidable, the data is in all likelihood very obsolete, and not applicable (or at best loosely applicable) to today's standard of care.