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Sequence Of Velcade And Revlimid Treatment May Not Matter In Many Multiple Myeloma Patients (ASH 2011)

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Published: Feb 10, 2012 11:28 am

The results of a recent retrospective analysis show that the sequence of treatment with Velcade and Revlimid may not have a significant effect on outcomes in multiple myeloma patients.

Only patients with kidney disease had significantly longer survival times if they received Velcade first.

The researchers from the Moffitt Cancer Center in Tampa, Florida, who conducted the analysis pointed out that further prospective trials are needed to confirm their findings.

The results were presented during a poster session at the 2011 American Society of Hematology (ASH) annual meeting in December.

Velcade (bortezomib) and Revlimid (lenalidomide) are generally viewed as the most effective drugs for the treatment of multiple myeloma. When patients relapse or do not respond to one, they are often treated with the other.

Although only Velcade is approved by U.S. and European regulatory authorities to treat newly diagnosed myeloma patients, Revlimid is frequently prescribed off-label in the U.S. as a treatment for newly diagnosed myeloma.

The authors of the ASH poster explain, however, that the optimal treatment sequence for the two drugs has not yet been established.

The researchers therefore analyzed data from 208 multiple myeloma patients who had been treated with Velcade followed by Revlimid, or vice versa, at their institution between January 2004 and August 2010. The goal of the analysis was to determine if one treatment sequence was associated with better outcomes than the other.

Of the 208 patients included in the analysis, 47 percent received Revlimid first and 53 percent received Velcade first.

The researchers found that response rates and median overall survival times did not differ significantly by treatment sequence.

The response rate to Velcade in patients who received Velcade first followed by Revlimid was 77 percent.  In patients who first were treated with Revlimid, the response rate when they later were treated with Velcade was 69 percent.

Interestingly, the response rate to Revlimid in patients who were treated with Revlimid first, followed by Velcade, was only 60 percent.  The response rate to Revlimid was noticeably higher -- 74 percent -- when patients were treated with Revlimid after having been treated first with Velcade.

Patients who received Revlimid first had an overall median survival time of 78.5 months, compared to 74 months for patients receiving Velcade first.

The difference in these survival times was not statistically significant.

However, the sequence of therapy did have a significant impact on survival in patients with kidney disease. Patients with kidney disease who received Velcade first had significantly longer median overall survival times (50.0 months) than patients with kidney disease who received Revlimid first (22.5 months).

Other factors, such as disease stage and chromosomal abnormalities, did not significantly affect whether survival was longer with a Revlimid-first or Velcade-first sequence of treatment.

For more information, please see abstract 3979 on the ASH 2011 meeting website.

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  • suzierose said:

    What was the scientific /clinical rationale to support that sequence of drug therapy would make a difference in outcomes to design such a trial?

  • Myeloma Beacon Staff said:

    Hi suzierose,

    Thanks for your question.

    The results presented in the poster were not from a trial designed to test the two sequences of treatment.

    Instead, the results are based on a retrospective analysis of data from myeloma patients treated at Moffitt between 2004 and 2010.

    The researchers went through the Moffitt patient records for that time period and found 208 patients who had been treated at different times with Velcade and with Revlimid.

    About half the patients happen to have been treated with Velcade first, then Revlimid later, while the other half happen to have been treated with Revlimid first, then Velcade later.

    So the researchers then split the sample of patients into a Velcade-Revlimid group and a Revlimid-Velcade group, and looked at the outcomes for those two groups.

    That's what was reported in the poster.

    Let us know if there is anything else about the study that we can clarify.

    And have a great weekend!

  • Michael Sullivan said:

    My mother, diagnosed with Multiple Myeloma in 2004 has been through exactly the sequence and regime as described above but here in the UK.

    She has kidney failure and has been through the Velcade cycle and is now receiving Revlimid. She has done extremely well and is still living as full a life as is possible - she is 77 this year and is so grateful to all the advances in drug therapy in Myeloma treatment that have been made DURING and since her initial diagnosis.

    She had not expected to live this long and frankly we have all been hugely impressed by the work that is being carried out in this field. I can only salute the many people on both sides of the Atlantic who are tackling this nasty disease. I thank you.


  • suzierose said:

    Hi Beacon staff!

    That's for focusing me on this being a retrospective study.

    My question is more focused about why do scientists THINK that sequence can impact pathogenesis of MM?

    What is the medical rationale for believing that it could? Have they seen a difference in cellular impact IN VITRO?

    What were they hypothesizing to design a retrospective comparative trial where sequence would be the criteria for a difference in outcomes?

    What about the pathogenesis of the disease leads them to believe that sequence of therapy can make a difference? Have they seen a difference in cellular resistance, in the lab/mice, based on sequence?

    Or what about the mechanism of action of the therapeutic agents leads them to beleive that the sequence could play a pivotal role in outcomes/survival/progression?

    I was wondering about the rationale of the science that motivated them to look for such a comparative difference...what about the progress of the disease creates sequence making a possible difference?


  • Dan D said:

    Good points. Let's face it: This study -- even without a rationale -- reflects our poor understanding of this disease and uncertainty as to the type and timing of treatment. As a result, anything goes -- and hey, retrospective studies are cheap.

    Yes, I am being a bit cynical. But on a more optimistic note, I commend current efforts by Landgren and others to gain real molecular insights into this disease so that patients can be given appropriate treatement at the appropriate time.

    And as to why sequence could be important, our still poor understanding of pathogenesis certainly can support some plausible scenarios. For example, I might predict that revlimid followed by Velcade would be preferred. Why? Revlimid acts mainly on the bone marrow microenvironment, whereas Veclade acts on the plasma cells. So first scorch the earth with revlimid and then use Velcade to chase down the stunned zombies, which will be unprepared and have nowhere to hide.

    But plasma cells first, then maybe I would begin selecting for highly resistant and mutant cells that will begin populating the welcoming marrow environment. It might then be more difficult for revlimid to eradicate this aggressive pool of cells, some of which may well be able to thrive in a hostile landscape.

    But I could probably argue the reverse as well. It is all loose and lacking in real evidence. This is really an example of research hoping for an interesting result -- where there may well be nothing to glean.

    Just my two cents. But I certainly wish we knew more about the details of pathogenesis. It would give me more comfort in deciding what treatment is best and when to begin. And horrors: it might even reveal a new way to manage this disease chronically or highlight a path to a cure.

  • ap623 said:

    The rationale for study design is as such:

    If you look at the mechanisms of actions of these two agents, one could hypothesize that lenalidomide would need an intact immune system to be most effective, as it is an immune modulator. Because bortezomib can deplete the immune system, it may antagonize the effects of immunomodulation, and therefore if given before lenalidomide therapy, may lead to worse outcomes (decreased response rates, overall survival, etc).

    The results of this study show that there was in fact no difference in these outcomes. While we do have to take the retrospective nature of this study with a grain of salt, this would be very difficult to study in a prospective up-front setting.

    I would agree with the above comments that very little is known in terms of the timing of therapy or which initial therapy to choose for patients, so this again adds another perspective.