[Beacon Staff]

ASH 2010 Multiple Myeloma Discussion - Day 1

by Beacon Staff on Thu Dec 02, 2010 4:40 pm

This forum thread can be used to discuss the proceedings of the American Society of Hematology (ASH) meeting that take place on Day 1 (Saturday, December 4) of the conference. Feel free to use this space to highlight interesting abstracts, summarize the presentations as they happen, ask questions, and discuss any relevant topics. Everyone is encouraged to participate.

Feel free to also check out the discussions for Day 2, Day 3, and Day 4.

[Julie Shilane]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Julie Shilane on Sat Dec 04, 2010 10:40 am

This morning’s education session began with a presentation by Dr. Ola Landgren from the National Cancer Institute and National Institutes of Health. Dr. Landgren spoke about monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma, precursor diseases of multiple myeloma.

Dr. Landgren’s study published last year showed that all multiple myeloma patients had MGUS initially, even though many of them were not diagnosed until the MGUS had already progressed to myeloma (see related Beacon news).

He emphasized the following points:

• The vast majority of patients with MGUS will never progress. Therefore, there is no need to screen the general public for MGUS.
• Patients who are diagnosed with MGUS should be risk-stratified, so they can be carefully monitored for progression.
• Patients with smoldering myeloma should be considered for clinical trials: trials studying the disease, risk of progression, and early treatment. Outside of clinical trials, smoldering patients should be observed, not treated, until progression. Early treatment may cause a more aggressive disease when the patient progresses/relapses.
• It is critical that we better understand both of these diseases.

[Julie Shilane]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Julie Shilane on Sat Dec 04, 2010 10:54 am

The second talk in the education session was presented by Dr. Raymond Comenzo from Tufts Medical Center in Boston. Dr. Comenzo spoke about AL amyloidosis, which is caused by misfolded light-chain proteins that aggregate and deposit in organs. There are a significant number of patients who have both myeloma and amyloidosis.

The symptoms of amyloidosis include fatigue, loss of libido, weight loss, difficulty with breathing (orthopnea or orthostasis), coughing, swelling, joint pain, abdominal discomfort, diarrhea, constipation, impaired taste (dysgeusia), numbness, tingling, and bleeding.

Many myeloma treatments are also effective against amyloidosis. Dr. Comenzo reported evidence that pomalidomide (Actimid) + dexamethasone or Velcade can be effective for treating amyloidosis. He also seemed hopeful about carfilzomib and monoclonal antibodies. However, studies have shown that Revlimid + melphalan + dexamethasone is not more effective than melphalan + dexamethasone. So he said Revlimid is no longer being developed for amyloidosis.

[Julie Shilane]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Julie Shilane on Sat Dec 04, 2010 11:46 am

Dr. Sagar Lonial from the Emory University’s Winship Cancer Institute gave the final presentation of this morning education session. Dr. Lonial spoke about the treatment of relapsed and refractory myeloma patients.

Dr. Lonial started off by saying that the good news is that patients with myeloma are clearly living longer than ever before. Unfortunately, once a patient relapses, especially if they have become resistant to Revlimid and Velcade, then survival remains poor.
Patients with myeloma are clearly living longer than in previous eras.

At relapse, he said the physician first needs to decide whether to treat the patient. If a patient has CRAB symptoms (calcium, renal [kidney], anemia, or bone involvement), then they need to be treated. Patients with only a biochemical relapse (such as the presence of M-protein) do not necessarily need to be treated. In the latter case, the physician should look at the aggressiveness of the previous relapse, risk of organ damage, and magnitude of the M-spike.

If a patient should be treated, the tough question is how to treat. Dr. Lonial broke relapsed patients into two groups:

• Indolent, slow, first relapse
• Aggressive, fast, multiple relapses

For patients in the first category (indolent, slow, first relapse), Dr. Lonial suggested likely single agent therapy with Velcade, Revlimid, or thalidomide. He would recommend Revlimid salvage therapy for patients initially treated with Velcade and have peripheral neuropathy. He would recommend Velcade salvage therapy for patients initially treated with Revlimid or thalidomide, patients who previously had a good or long response to Velcade, or patients with kidney problems. He would recommend a stem cell transplant for patients who did not initially have a transplant or those who had a long remission after the first transplant (18 to 24 months). He pointed out that the duration of the second transplant is usually shorter than the first. Patients who have low blood cell counts that prevent them from tolerating treatment with novel agents may not have many other options besides a transplant.

For patients in the second group (aggressive, rapid, multiple relapses), Dr. Lonial said the options are salvage therapy with chemotherapy, chemo plus Revlimid or Velcade, or a stem cell transplant. In this group, the efficacy of a transplant is likely to be short lived, but it is a quick way to control the disease, which can be quickly followed up with salvage therapy.

Dr. Lonial was particularly excited about the emerging therapies: pomalidomide, carfilzomib, panobinostat and Zolinza (vorinostat) in combination with novel agents, perifosine, and elotuzumab in combination with Revlimid/dexamethasone.

[Ricardo]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Ricardo on Sat Dec 04, 2010 6:15 pm

Thanks, Julie (and the rest of the Beacon team) for this great coverage of the ASH meeting. These quick summaries almost make me feel like I'm attending the meeting.

R.

[Julie Shilane]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Julie Shilane on Sat Dec 04, 2010 6:42 pm

Thanks, Ricardo! I'm glad to hear you find the summaries interesting and helpful.

I just got out of an afternoon session and will be posting on that in just a minute. Then I'm off to the evening's poster session.

[Julie Shilane]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Julie Shilane on Sat Dec 04, 2010 6:43 pm

This afternoon, there was a scientific session about myeloma stem cells.

The most relevant talk was given by Dr. William Matsui from the Johns Hopkins University School of Medicine in Baltimore. Dr. Matsui spoke about the origin of the myeloma stem cell. He believes that there are myeloma stem cells, but that they’re rare. Studies indicate that 1 in 10,000 or 1 in 100,000 cancer cells are cancer stem cells.

In myeloma, plasma cells make up the majority of tumor cells, explained Dr. Matsui. Diagnoses are generally made based on malignant plasma cells, and they are responsible for the symptoms of myeloma. However, B cells are probably the source of myeloma stem cells.

Dr. Matsui described that B cell-based strategies for targeting myeloma stem cells have been pursued, but the self-renewal of cancer stem cells needs to be pursued. He suggested that the plasma cells should be reduced using high-dose therapy, then the cancer stem cells can be targeted. He also suggested that among the current myeloma therapies, myeloma stem cells are most sensitive to Revlimid, then dexamethasone, and then Velcade.

[Ricardo]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Ricardo on Sat Dec 04, 2010 7:11 pm

Hi Julie,

Thanks for the additional update.

The whole concept of "myeloma stem cells" is a bit confusing to me. These are cells that are supposed to turn into myeloma cells, right? Are they thought to be the source of all the myeloma cells in a myeloma patient's body, or just some part of them?

Also, did the audience at the session seem to take it for granted that there really are "myeloma stem cells." From what I just read in this Wikipedia article about cancer stem cells,

http://en.wikipedia.org/wiki/Cancer_stem_cell

there seems to be some debate about the existence of such cells.

I'm going to have to go look up what B cells are. I found this Wikipedia description,

http://en.wikipedia.org/wiki/B_cells

but I'll have to digest it a bit.

Thanks again,

R

[Julie Shilane]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by Julie Shilane on Sat Dec 04, 2010 10:40 pm

Hi Ricardo,

Great questions!

Similar to the way stem cells in your bone marrow produce new blood cells (red, white, and platelet), cancer stem cells are believed to create new cancer cells. Myeloma stem cells would create myeloma cells, and other types of cancer stem cells would create those types of cancers. It's also believed the cancer stem cells may be the cause of relapse. Treatment may kill the regular myeloma cells, but myeloma stem cells would be more difficult to kill off and then could begin to create new cancer cells.

There's a lot that is still unkown about cancer stem cells, though. There may be experts out there who don't believe in them, but there didn't seem to be any resistance to the idea of cancer stem cells at today's session.

B cells are immune cells. They can be activated to produce antibodies, at which point, they are known as plasma cells.

[NStewart]

Re: ASH 2010 Multiple Myeloma Discussion - Day 1

by NStewart on Sat Dec 04, 2010 11:45 pm

Julie-
Thank you for today's coverage of the conference and for your defining myeloma stem cells and B cells. I know that the researchers at Penn are working on trying to identify the various types of stem cells. They believe that there are cancer stem cells and that is why there are relapses, often many years after treatment for the original cancer.
Nancy