Today was the second day of the American Society of Clinical Oncology (ASCO) annual meeting.  Although the day has not been as busy with myeloma-related presentations as tomorrow and Monday will be, there still were some interesting presentations and discussions.

The Beacon published an update earlier today with news from a morning poster session that featured several presentations related to multiple myeloma (see related Beacon ^[1] news).

This article covers material from an early-afternoon education session that was titled: "Controversies in Myeloma: Induction, Transplant, and Maintenance."

The education session included three talks by leading myeloma experts.

Induction Therapy

The first presentation (full-text article ^[2]) during the education session was given by Dr. Vincent Rajkumar from the Mayo Clinic.  During his presentation, he discussed the options available to patients for their very first treatment after diagnosis -- that is, the treatment generally known as "induction therapy."

There are many options for induction therapy.  Dr. Rajkumar said during his presentation that he has found at least 20 different induction regimens discussed in the scientific literature.

The challenge for physicians and patients is determining what treatment regimen best fits with a patient's particular characteristics.

Myeloma specialists often classify patients using at least three different sets of criteria: general patient characteristics, such as age, and physical condition; how extensive the myeloma is in the patient's body; and how aggressive the patient's myeloma is.

Of these three sets of criteria, Dr. Rajkumar believes the aggressiveness of the myeloma is the most important when selecting a patient's induction therapy.

Furthermore, the aggressiveness generally depends on which chromosomal abnormalities are present in the patient's myeloma cells.  Certain groups of abnormalities determine whether the myeloma is "standard risk," "intermediate risk," or "high risk."

Based on the research he has done and his experience treating patients, Dr. Rajkumar believes the choice of a myeloma patient's induction regimen in most cases should be based on the risk classification of the patient's myeloma.

For example, he believes that for most patients with standard-risk myeloma, the best induction regimen is either Revlimid ^[3] (lenalidomide) combined with low-dose dexamethasone ^[4] (Decadron) or a three-drug combination commonly referred to as VCD or CyBorD; it includes Velcade ^[5] (bortezomib), cyclophosphamide ^[6] (Cytoxan), and low-dose dexamethasone.

For intermediate-risk patients, he generally prescribes VCD as an induction regimen.

And, for high-risk patients, Dr. Rajkumar usually prescribes the combination regimen of Velcade, Revlimid, and low-dose dexamethasone.  He believes, however, that VCD also is a viable option for this group of patients.

One point that Dr. Rajkumar made several times during his presentation is that choosing the right induction treatment for a patient is not just about knowing what options might be best for the patient.  It's also about knowing what options to avoid.

He believes, for example, that experience and research show that regimens involving Velcade should involve only once-weekly dosing of the drug, rather than the more frequent dosing originally used when the drug first became available.

Dr. Rajkumar has made his presentation available ^[7] for download and viewing as a courtesy to The Beacon’s readers.

Stem Cell Transplantation

Following Dr. Rajkumar’s presentation, Dr. Amrita Krishnan from City of Hope National Medical Center spoke about stem cell transplantation in multiple myeloma (full-text article ^[8]).

Stem cell transplants did not become common among myeloma patients until the past 10 to 15 years, after several clinical trials showed that high-dose chemotherapy followed by a stem cell transplant significantly improves myeloma patient survival.

Yet those clinical trials were conducted in what some would consider a different era.  In particular, they were carried out at a time when the initial treatments most myeloma patients received did not include any of the so-called novel anti-myeloma drugs: thalidomide ^[9] (Thalomid), Velcade, and Revlimid.

The novel myeloma treatments have significantly improved survival and led to a number of important questions about the role of stem cell transplantation in myeloma.

Dr. Krishnan said there are really three main questions about transplantation and myeloma: "When?," "Who?," and a catch-all "What if?".

The "When?" question has two parts.  First, how long should patients receive their initial anti-myeloma therapy prior to stem cell transplantation?  Should, for example, they be given just a standard number of cycles of initial therapy -- say four cycles?  Or more?

Second, should patients receive a transplant immediately after their first anti-myeloma regimen has ended, or should they wait to do a transplant after they have relapsed and had a second round of anti-myeloma therapy?

Dr. Krishan believes that the jury is still out on both of these questions.  She pointed out that a major trial is underway which is specifically designed to answer the second question.  Results from that trial will be available in a year or two.

The "Who?" questions deals with the issue of which patients should -- and should not -- be considered transplant eligible.

In the past, an age cutoff -- often 65 years -- was typically used to divide myeloma patients into transplant-eligible and transplant-ineligible groups.  Dr. Krishnan, however, believes that research now shows that age is not really the best criterion.  Transplants can be safely and effectively carried out in patients much older than 65 years, as long as the patients are physically fit enough to undergo the procedure, and as long as dose adjustments are used to ensure the patient's safety.

The "What if?" question addresses special cases, such as patients with kidney issues, patients with high-risk chromosomal abnormalities, and patients who have the option of receiving a donor transplant using stem cells from a close relative.

Dr. Krishnan feels that recent research gives rather clear guidance as to what should be done in regard to the first two special cases.

On the third issue, though, she believes more research is needed.  For more on that subject, see, for example, the Beacon ^[10] news article discussing research presented by Dr. Krishnan at the 2010 American Society of Hematology meeting.

Maintenance Therapy

The last education session presentation was given by Dr. Michel Attal from the Purpan Hospital in Toulouse, France.  The focus of his presentation (full-text article ^[11]) was on whether there is evidence to support the use of specific anti-myeloma drugs as maintenance therapy after either induction therapy or after induction therapy followed by a stem cell transplant.

Not long into his presentation, Dr. Attal laid out a useful framework for thinking about whether specific drugs should be used for maintenance therapy.  The key considerations, he said, are a drug's impact on overall survival, progression-free survival, and patient quality of life when the drug is used as maintenance therapy.

Thus, if maintenance therapy with a drug improves overall survival with no significant negative effect on patient quality of life, it clearly is a useful maintenance therapy.

If, on the other hand, maintenance therapy with a drug has no survival benefit and it reduces quality of life, it clearly is not a useful maintenance therapy.

Based on this framework and a review of clinical trial evidence, Dr. Attal believes there is little or no justification for using chemotherapy agents, interferon, or prednisone ^[12] as maintenance therapy in multiple myeloma.

But what about the novel anti-myeloma agents thalidomide, Velcade, and Revlimid?  What is the evidence for or against using them as maintenance therapy?

Dr. Attal stepped through the clinical trial results that shed light on whether or not these drugs are well suited for use as maintenance therapy.

In regard to thalidomide, he explained that several studies show maintenance therapy with the drug can yield an overall survival benefit.  Dr. Attal seemed hesitant, however, to endorse using thalidomide as maintenance therapy.   Such therapy, he explained, seems to benefit a rather narrow group of patients.

As for Velcade, Dr. Attal believes that clinical trial results are currently too limited to conclude whether or not maintenance therapy with the drug is worthwhile.

Finally, in regard to maintenance therapy with Revlimid, Dr. Attal believes that conflicting clinical trial results mean that it is too early to draw any conclusions.  On the one hand, three major clinical trials clearly demonstrate that Revlimid maintenance positively impacts progression-free survival.  Only one of those trials, however, showed a benefit in terms of overall survival.

Furthermore, all three trials showed that maintenance therapy with Revlimid is associated with non-trivial side effects, including an increased risk of second cancers (see related Beacon ^[13] news article).

Myeloma presentations from Day 3 and Day 4 will also be summarized in Beacon ASCO daily updates to be published tomorrow and Monday.  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 ASCO meeting, see The Beacon’s full ASCO 2012 ^[14] coverage.