Good day, myeloma world.

Monday's tend to be quiet here at Myeloma Morning Headquarters – at least when it comes to new research that needs to be reviewed and summarized. Today is no exception. There was no new myeloma-related research when we checked this morning, and just one or two news items.

We do have a few things, however, that we'd like to review with you.

First, we mentioned last week that this month's issue of the Journal of Oncology Practice (JOP) has an article, with two commentaries, on the topic of personalizing therapy for multiple myeloma. All the contributions are by leading multiple myeloma specialists, so we thought we would look at them in more detail together with you today.

Second, there was a lot of interest in yesterday's edition of Myeloma Morning and, in particular, the part of the report about the possible anti-myeloma activity of lansoprazole (Prevacid). So we thought we would look a bit more at that study.

Personalizing Multiple Myeloma Therapy

The main article about personalizing myeloma therapy that we will look at today is by Drs. Sagar Lonial and Ajay Nooka of Emory University. The article is titled “Myeloma Is Not A Single Disease” (abstract).

We should note from the outset that this article – and the two commentaries that accompany it – focus on personalized treatment for newly diagnosed multiple myeloma patients. One can imagine concepts similar to those discussed in these articles being applied to the treatment of relapsed multiple myeloma. But, in the spirit of open disclosure, we want to make it clear upfront that the articles are about … well … upfront therapy.

The Emory researchers begin their article by noting that multiple myeloma is similar to just about every cancer in the sense that, when you look at the cancer cells with a microscope, they all look basically the same. However, once you start looking closer – for example, at the genetic characteristics of the cells – you begin to find important differences.

The more detailed ways of investigating myeloma cells can identify 5, 10, 15, or even more types of myeloma that differ in their behavior and response to therapy. In day-to-day medicine, this is reflected in the fact that seemingly similar multiple myeloma patients can have widely different responses to the same sequence of treatments.

So one dimension that could be used to tailor therapy for multiple myeloma patients is the genetic dimension – the chromosomal abnormalities the disease has, or its "gene expression profile" (GEP), or other, even more sophisticated, characterizations.

But there is also an important second dimension which needs to be considered, Drs. Lonial and Nooka write. That dimension is a patient's general health, their “functional status.” Is the patient strong, or is she or he frail?

Traditionally, this “fitness” / “frailty” dimension has been used to decide whether or not a multiple myeloma patient should undergo an autologous stem cell transplant as part of initial therapy. Drs. Lonial and Nooka argue, however, that this need not be the case. Lower doses of melphalan can be used during the transplant process, making it tolerable for a wide range of patients.

Instead, a patient's frailty may be more important, Drs. Lonial and Nooka write, for deciding whether patients should get intensive, three-drug (“triplet”) initial therapy, or if they get just two-drug (“doublet”) therapy.

The authors note that there are different scales and indexes that have been proposed for assessing how frail a patient is. They also note that there is research constantly ongoing into ways to assess whether a patient has high-risk versus standard-risk disease. The authors believe, however, that results of chromosomal abnormality testing using FISH are still the most reliable way to categorize a patient's risk.

Recommended Approach To Tailoring Therapy

Overall, the Emory researchers recommend tailoring initial therapy for newly diagnosed multiple myeloma patients by first deciding whether they are fit enough to undergo a transplant.

For those who are fit enough for a transplant, the authors recommend initial therapy with Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone, followed by a transplant.

The authors believe recent trial results argue in favor of triplet versus doublet therapy, and there is evidence that pairing drugs such as Revlimid (an “immunomodulatory agent”) with drugs such as Velcade (a “proteasome inhibitor”) is a better strategy than, for example, pairing Velcade with a drug such as cyclophosphamide in regimens such as CyBorD (cyclophosphamide, Velcade, and dexamethasone).

The authors also believe that recent trial results argue in favor of all transplant-eligible myeloma patients having a transplant as part of upfront therapy. They rely, in particular, on the results of the French “IFM” trial that have been presented at various scientific meetings.

The main place that the researchers recommend tailoring the therapy of transplant-eligible newly diagnosed patients is in regard to post-transplant treatment. There, they recommend intensive, triplet maintenance therapy for patients with high risk disease at diagnosis, and Revlimid-only maintenance for standard risk patients.

For newly diagnosed patients too frail to undergo a stem cell transplant, the authors recommend treatment with a doublet – Revlimid and dexamethasone, or Velcade and dexamethasone – for patients with standard risk disease, and a modified (reduced) dose Revlimid, Velcade, and dexamethasone (RVD) triplet for patients with high-risk disease.

“As we consider how to tailor treatment to individual patients with myeloma,” the Emory researchers write at the end of their article, “the current literature suggests that the use of biology-driven treatments, taking into account functional status and genetics, is likely the first and most important step. The incorporation of these agents with biology-based approaches will likely yield the best and most effective treatments as we continue to learn how best to target the many mutations found in patients with myeloma.”

Comment By Dr. Richardson

In his comment on the paper by Drs. Lonial and Nooka, Dr. Paul Richardson of the Dana-Farber Cancer Institute in Boston agrees with their opening premise – that multiple myeloma is not a single disease. He does take issue, however, with two points made by the Emory researchers (extract).

The first point will be a difficult one for many of our readers to hear being debated. But it's important to understand that researchers are debating the issue.

In particular, Dr. Richardson notes that, in their article, Drs. Lonial and Nooka write that it is possible that some 10 to 15 percent of multiple myeloma patients are being cured with current treatments for the disease.

Dr. Richardson believes such statements are misleading. “This remains to be established,” he writes, “and it must be recognized that myeloma, to date, continues to be an incurable disease in the long term.”

Second, Dr. Richardson questions the recommendation that all fit newly diagnosed multiple myeloma patients should undergo a stem cell transplant. This recommendation, he says, “must be viewed with some caution.”

Dr. Richardson then continues, “As our patients live longer and an increasing proportion can anticipate median survivals in excess of 10 years, it becomes just as important to consider long-term adverse effects as it is acute toxicities.”

Comment By Drs. D’Agostino And Palumbo

In a second commentary, Italian myeloma specialists Drs. Mattia D’Agostino and Antonio Palumbo (extract) largely agree with the points made by Drs. Lonial and Nooka in their article. The Italian researchers mainly argue that greater evidence is needed to understand, for example, exactly how to tailor therapy based on the genetic characteristics of a myeloma patients disease.

Similarly, they believe that existing tools for assessing the frailty of myeloma patients are certainly helpful. They can help doctors avoid overtreating frail patients, while also avoiding the undertreatment of healthy patients. But these tools need to be tested more to help determine what treatments are best for very frail, frail, and less frail patients.

The Anti-Myeloma Activity Of Lansoprazole (Prevacid) - Round 2

There was a lot of interest in the study we summarized yesterday that found that the heartburn medication lansoprazole (Prevacid) may have anti-myeloma activity (abstract).

In fact, there was so much interest, we thought we should remind people of a few things.

First, as we mentioned yesterday, the research on this issue was carried out in the laboratory. No multiple myeloma patients were treated with lansoprazole to see if it might have anti-myeloma activity.

Second, as we also wrote yesterday, many drugs are active against multiple myeloma cells in the laboratory, but end up not having much of an effect on the disease when they are actually used in multiple myeloma patients. So preclinical (laboratory) studies always have to be interpreted with caution.

We will add a few more details that we hope will further put things in perspective.

One is that the authors of the lansoprazole study investigated the drug's anti-myeloma activity by exposing only two different myeloma cell lines to the drug. While some preclinical studies involve just a single myeloma cell line, it is increasingly common for such studies to investigate a drug's impact on 4, 5, or 6 myeloma cell lines.

Also, more and more preclinical myeloma studies test the impact of a drug on myeloma cells found in laboratory animals (models), usually mice. This was not done in the lansoprazole study.

So, as we said yesterday, the results of the study are interesting, but one shouldn't assume by any stretch of the imagination that it's been proven that lansoprazole fights multiple myeloma when the drug is taken by myeloma patients.

But stay tuned. We suspect we'll have more on this research.

Quickly Noted

• The Swedish biopharmaceutical company says that it will soon start enrolling patients in its Phase 2 clinical trial of BI-505 in patients with multiple myeloma (press release).
• The U.S. biopharmaceutical company Cellectar Biosciences has set the price it will charge for its stock in an upcoming public offering. The stock sale will help fund the company's development of CLR 131 as a potential new multiple myeloma treatment (press release).