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Tips For Making Sense Of The Research Results Presented At This Year’s ASH Annual Meeting

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Published: Dec 8, 2012 6:17 am

Today marks the first day of presentations and poster sessions at the 2012 American Society of Hematology (ASH) annual meeting.

The meeting, which is being held in Atlanta this year, will provide the multiple myeloma community with a veritable deluge of new research about existing myeloma treatments as well as therapies that are still under development.

As was the case with previous ASH annual meetings, The Myeloma Beacon will be covering this year’s meeting in detail.  Beacon readers can expect regular updates as the meeting proceeds, and additional, in-depth articles on specific topics once the meeting has ended.

In other words: There are going to be a lot of study results to interpret and make sense of.

That leads to some obvious questions, such as: How exactly should the results be interpreted?  What is important, and what is not important?  What should Beacon readers be focusing on when they are reviewing all the results coming out of the meeting?

To help with these sorts of questions, the Beacon editorial and writing team has put together a “cheat sheet” of sorts – a list of the key things Beacon readers should be looking for when they review research results presented at ASH (or, for that matter, any scientific meeting, or in journal articles).

The tips that follow focus primarily on interpreting results for studies that explore how effective and safe a particular myeloma therapy is.  Some of the tips, however, also are applicable to interpreting results from other kinds of studies – for example, studies focused on how often certain side effects occur during the treatment of multiple myeloma.

The tips are listed as a series of questions readers generally will want to answer as they review the results of a study.  The questions concern the following topics: the patient population of the study, the nature of the treatment being investigated, the effectiveness of the treatment, the safety of the treatment, and the type of study that was carried out.

What is the patient population covered by the research?

The patient population is perhaps the most fundamental issue to be aware of when reviewing the results of just about any study involving multiple myeloma patients.

It is so critical because just about any myeloma treatment will show higher levels of effectiveness – reflected in higher response rates and longer survival – in studies involving newly diagnosed patients than in patients who have been previously treated.

Thus, the first thing to determine about a study is whether or not it involves only newly diagnosed patients, only relapsed or refractory (treatment-resistant) myeloma patients, or a mix.

If a study involves only relapsed and/or refractory patients, a key statistic to look for is the median number of previous treatments that patients in the study have received.

Generally for studies involving relapsed/refractory patients, the median number of previous therapies will be either two or three (for studies that limit enrollment to patients with one to three, or perhaps four, lines of previous therapy), or it will be five or greater for treatments being tested on patients with few – if any – other treatment options.

The other aspect of the patient population to consider is what previous treatments the patients may have received.  Here, the key is whether or not the patients have received treatment with a drug similar to – or the same as – a drug included in the treatment regimen being tested during the study.

Response rates will be higher for a treatment regimen being tested on a patient population which, by design, has excluded patients who have never been treated with a similar (or the same) treatment in the past.

For example, if a treatment regimen includes Revlimid (lenalidomide), then it is important to know if patients in the study were previously treated with Revlimid or with drugs in the same class as Revlimid, such as thalidomide (Thalomid) or pomalidomide.

The same holds for Kyprolis (carfilzomib), Velcade (bortezomib), and ixazomib (MLN9708), which are in the same class of drugs.

How many drugs were in the treatment regimen that was tested, and how long were the patients treated with the regimen?

Generally, the more drugs that are included in a treatment regimen, the greater the response there will be among the patients treated with the regimen.

Thus, when looking at clinical trial results, it is important to note whether the drug that is the focus of the study was administered by itself, or in combination with a steroid such as dexamethasone (Decadron) or prednisone, or in combination with a steroid and another anti-myeloma agent.

The acid text for a potential new drug, for example, is whether it generates a meaningful response on its own, or with just a steroid.

Similarly, a high response rate for a new drug is not as impressive if the response rate was seen when the drug was combined with a steroid and an existing myeloma treatment, such as Revlimid or Velcade.

Length of treatment matters as well.  Response rates usually will be higher in patients who receive a treatment regimen for an extended period of time – for example, six months or a year – versus patients given the same regimen for a shorter period of time.

How effective is the treatment?

This, of course, is probably the most critical question to ask when looking at the results of a research study.

Response Rates

Typically, the effectiveness of a treatment will be measured by various response rates, such as how many patients achieved a complete response or how many had a partial response.

A useful way to make response rate comparisons across different studies is to focus on the overall response rate reported for a treatment, which usually is defined as the percentage of patients who achieved a partial, very good partial, or complete response.

The higher the overall response rate, the more effective the treatment.

In newly diagnosed patients, three-drug combinations are achieving overall response rates of 90 to 100 percent.

In patients with two or three previous lines of therapy, three-drug combinations have achieved an overall response rate of 80 to 85 percent.

In heavily pretreated myeloma patients with five previous lines of therapy, overall response rates have been observed in the 20 to 30 percent range for drugs administered alone or in combination with a steroid.

Because overall response rates among newly diagnosed patients are now regularly in the 90 to 100 percent range, it is becoming common in studies with newly diagnosed patients to look at not just the overall response rate, but also measures of the depth of response.

The depth of response is usually captured by the share of patients achieving either a complete response or a stringent complete response.

Among newly diagnosed patients treated with three-drug combinations, those two rates have reached 90 and 60 percent, respectively


Of course, the most important measure of a myeloma treatment’s effectiveness is not its response rate.  It is the treatment’s impact on how long the patients live.

In the medical literature, the length of time that a patient lives after starting treatment with a specific therapy is known as the patient’s “overall survival.”

If a study reports a treatment’s impact on overall survival, that is a particularly important statistic to pay attention to.

Overall survival may be reported as the percent of patients in the study who lived a certain period of time -- such as one year, two years, or five years.   Or it may be reported as the median amount of time patients in the study lived after initiation of treatment.

Not all studies involving myeloma patients report overall survival statistics.  This is because it can be challenging to track patients long enough to measure the impact of a treatment on overall survival.

As a result, studies often report a treatment's impact on what is called "progression-free survival."  The progression-free survival for an individual patient is the length of time between (a) the start of the treatment being investigated in a study, and (b) the point at which the patient's myeloma stops responding to the treatment and begins to progress again.

In studies involving myeloma patients who have had several previous therapies, progression-free survival is generally viewed as a good indicator of the impact a treatment will have on overall survival.  In such patients, a treatment that improves progression-free survival is also likely to improve overall survival.  So the progression-free survival statistics for such studies are worth paying attention to.

This is not necessarily the case for studies involving myeloma patients with few (or no) previous therapies.   In those studies, treatments that improve progression-free survival do not always improve overall survival. As a result, the progression-free survival statistics for such studies should be viewed with more caution.

How safe is the treatment?

Studies investigating a specific myeloma treatment generally report a long list of side effects that were observed among the study patients.  The list usually includes how frequently each of the most common side effects was seen in the study patients.

To capture the most important aspect of these results, it can be useful to look for how many patients experienced particularly severe side effects – side effects which, in the medical literature, are classified as “Grade 3” or higher.

If a large share of patients in a study experience such side effects, that can be a sign that the treatment may not be well suited to use outside of the clinical trial environment.

All side effects, however, are not created equal.

For example, myeloma specialists often are not as concerned about side effects involving lower blood cell counts, since such side effects usually can be controlled by reducing or temporarily halting the dosing of the treatment being investigated.

In contrast, side effects of a more permanent nature – such as damage to the heart, kidney, or liver – are typically of greater concern to physicians.

Are the research results from a prospective – or retrospective – study?

Most of the key research reported at ASH will be from studies that have been carried out “prospectively.”  Prospective studies are ones where the research is designed in advance, patients are recruited for a study based on specific criteria, and the treatment investigated during the study is administered according to very specific rules.

Retrospective studies, in contrast, are studies where treatment results are collected “after the fact.”  Researchers determine a subject they are interested in exploring, look through existing patient data to identify those who have been treated in ways that will shed light on the question the researchers want to explore, and the patient data are then collated and analyzed to see what can be learned.

Physicians typically have greater faith in results from prospective studies because they usually give a more unbiased view of a treatment’s efficacy and safety.

A retrospective study examining a specific myeloma therapy, for example, will find it difficult to control for the fact that many patients in the study received the therapy precisely because their physicians thought it would be the best one for them.

As a result, the retrospective study will tend to report results more favorable to the treatment than a properly designed prospective study.

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Myeloma presentations from later today as well as each of the remaining days of the ASH 2012 meeting will be summarized in ASH daily updates to be published at The Beacon the next few days.  Additional coverage of key research results from the meeting will continue throughout the rest of the week in individual, topic-specific news articles.  For all Beacon articles related to this year’s ASH meeting, see The Beacon’s full ASH 2012 coverage.

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  • Sherry Legier said:

    Another thing that is important to look at, but is often not mentioned in the reports are what the myeloma genetic makeup is of the patients involved in the study. For instance, most of the patients whom responded well may have standard risk myeloma, whereas those who didn't response so well may have some type of translated chromosomes.

  • Gary said:

    This is an excellent summary. Thank you so much. Despite much rhetoric, is is disappointing that Quality of Life is not measured in most of these studies.

  • Steve Cochran said:

    Yes....a very well written "cheat sheet", as you put it. And to Gary's point regarding QOL... HEAR, HEAR!!

  • Boris Simkovich said:

    Thanks, everyone, for the comments.

    Gary and Steve - More and more studies with myeloma patients are measuring patient quality of life (QOL) in addition to the standard efficacy and side effect statistics. However, it isn't yet commonplace.

    Sherry - As you know, it is not very common for clinical trials with myeloma patients to specifically target patients with certain genetic / chromosomal characteristics. There are exceptions. But most studies usually include patients with any and all genetic characteristics, which means that the studies aren't as different from one another as can be the case, for example, if one study targets newly diagnosed patients and another targets heavily pretreated patients.

    Of course, when digging deep into the results for a particular study, it is useful to see if the authors report results separately for different groups of patients based on their genetic characteristics. This is particularly important if you happen to be a myeloma patient whose disease has genetic characteristics that can make it hard to treat (higher risk).