[SBarro]

New poster: story, and doubts about Zometa

by SBarro on Wed Dec 10, 2014 2:25 pm

After over two months of back/spine injuries, with hospitalization and a misdiagnosis, I was finally diagnosed through a bone marrow biopsy with nonsecretory myeloma (no M spike) in April 2014, stage 2, with 80% of bone marrow plasma cells cancerous. My oncologist says that my form of myeloma, which does not contain free light chains, is easier to treat than other forms. I underwent six months of primary therapy using Cytoxan [cyclophosphamide] and dexamethasone infusion plus Velcade injection once per week, with 21 days of 15 mg Revlimid pills on a 28 day cycle. I also received infusions of Zometa once per month.

At the end of the six months, the percent cancer cells dropped to 20%. I was a bit disappointed because my oncologist remarked that approximately 45% of patients at that point experienced “remission,” which he defined as under 5% cancerous cells. I don’t know if that percent figure applies to all his myeloma patients, or to just the patients with my type of myeloma.

After a couple weeks with no treatment, I started a new regimen that eliminated the Cytoxan because continued use of it would damage my bone marrow. I’m now in the second month of this second treatment schedule, which is the same as the first, excluding the Cytoxan, and 20 mg of dexamethasone is taken in pill form, once per week, on the day of the Velcade injection. My oncologist said that all the doses I’m taking now are the same as those I took in the first six- month regimen.

The overall plan is to beat down the percent cancer to under 5%, after which my oncologist will recommend me for an autologos stem cell transplant. His original estimate for the length of this second regimen was about three months. He remarked that all his patients who have had the auto transplant after remission have come away with undetectable cancer cells, though they do undergo 10 mg Revlimid daily maintenance. I’m not sure whether the 21/28 day regimen is followed with their Revlimid.

Compared to many, the side effects I experienced were rather small. There was mild edema in my feet, which cleared up. I have minor mouth sores. I noticed a small red rash twice on my upper arm that disappeared after a day, and I experienced only at the beginning of the second round noticeable fatigue in the later part of the day.

Perhaps the worst symptom has been bone pain in my lower back and torso. I started the first round of chemo while taking narcotic pain killers, but these pains subsided greatly, and I had no need for any pain killers for the last several weeks of the six-month round of chemo. However, bone pain did return at the start of this second round, and it has now settled mainly in my lower back.

The Cytoxan and Velcade, however, destroyed my sense of taste, which is a quality of life issue. Now, during this second round, I have very little sense of taste, because of the Velcade alone, and lately my lower back pains have increased.

Two weeks ago, I had an X-ray bone survey, and they discovered that all my lumbar vertebrae, save one, have compression fractures, with approximately 10% compression, and these are relatively new. My oncologist explained that these fractures can occur with little force, and they have perhaps occurred recently because the packed in myeloma cells, in hollowing out the bones, do provide support. So when the myeloma cells are destroyed (which is good news), the vertebrae have less support and are more subject to fracture. It's interesting in that I have no recollection of causing any recent injury, though I exercise daily by walking on a treadmill, and I'm wondering whether I should stop that, or at least go very mildly.

It’s my impression that perhaps the Zometa is not working very well for me. I read that it reduces bone fractures by only 60%, and it takes at least six months to be effective. It’s now nine months since I started Zometa treatment, and its effectiveness is not complete. Because of this, I’m considering the calcium supplement, calcium aspartate anhydrous, an organic molecule extracted from plants and marketed by Elixir.

Although the company links to impressive research and clinical studies, I wonder how well this supplement will work for me and others, and of course, whether it's a scam. Elixir makes known that calcium in this form is 92% verifiably absorbed by the body, whereas all other standard supplements, with Vitamin D, are absorbed from about 10% to 25%. There is also data showing bone density increases in older adults after 30 days of usage, which I think is remarkable. My oncologist seemed interested in this product and said he’d study it.

There’s also something distasteful (excuse the word) in the way Zometa and all other bisphosphonates work because they thwart nature’s process of bone metabolism by killing the osteoclasts, which are living cells that remove old bone material. Thus, new bone material must be deposited by the osteoblasts over the bone material nature decided must be removed.

I wonder what ideas might be offered by other members of this impressive forum, which I am very grateful for. I’ve been reading it for a month now, and this is my first posting.

Many thanks in advance for any of your thoughts.

[Dr. James Hoffman]

Re: New poster: story, and doubts about Zometa

by Dr. James Hoffman on Wed Dec 10, 2014 6:16 pm

There are a few comments I would make in response to your post:

1. Non-secretory myeloma does have the advantage of not having injurious free light chains that can cause kidney damage, but, on the other hand, it is harder to monitor (generally need repeat bone marrow biopsies). So it is not truly better or worse, just different.
2. Data suggests that auto stem cell transplant is beneficial for those that achieve at least a 50% reduction in their disease. So <5% is a nice target, but not absolutely needed.
3. You seem to have had over 6 months of Revlimid already. Typically we don't go much beyond this before stem cell collection, as prolonged Revlimid exposure can make stem cell collection a little more difficult.
4. I am not sure what he meant by "all his patients who have had the auto transplant after remission have come away with undetectable cancer cells, though they do undergo 10 mg Revlimid daily maintenance." It is true that most patients transplanted in complete remission come out of transplant in complete remission. But most patients that get complete remission will still be there 3 months later even without the transplant. So this is not really saying very much.
5. For compression fractures with significant pain, kyphoplasty can sometimes help.
6. In terms of "My oncologist explained that these fractures can occur with little force, and they have perhaps occurred recently because the packed in myeloma cells, in hollowing out the bones, do provide support". This is not true. Myeloma cells are not structural components of our skeleton. Effective treatment of myeloma decreases fracture risk, not increasing it.
7. It is impossible to gauge how well Zometa is helping one person in terms of fracture risk., but if a 100 of you took it versus 100 that didn't, the ones that took it would definitely have fewer fractures ... and perhaps even better overall survival. So it is an important part of the treatment plan. And in terms of what nature intended as it relates to bis­phos­phonates, remember, nature doesn't account for myeloma, and myeloma cells enhance osteoclast (bone-destroying cell) activity at the expense of osteoblast (bone-building) activity. So, in that sense, you can envision the Zometa as simply 'leveling the playing field'.

Hope this helps!

[Mister Dana]

Re: New poster: story, and doubts about Zometa

by Mister Dana on Thu Dec 11, 2014 2:38 am

SBarro,

Thank you for writing up your story and providing the detail and perspective. If you go to the forums home page and do a "search all forums" for the words "nonsecretory" and "secretory", you will see that there have been several discussion threads about nonsecretory multiple myeloma, including a new one started just last month, plus my story (which I typed up this past summer while I was hanging out at the Mayo Clinic getting my autologous stem cell transplant).

Just like you, I had CyBorD chemo weekly and Zometa monthly until shortly before I got the high dose melphalan and transplant. The ill effects of those treatments have worn off completely, except for a little residual ankle swelling. I hope you, too, get back to near-normal.

Keep posting here if you can. Hang in there, and best of luck.

Mister Dana (now a year post-diagnosis)

[SBarro]

Re: New poster: story, and doubts about Zometa

by SBarro on Thu Dec 11, 2014 7:31 pm

Dr. Hoffman, thank you for your clarifications and informed comments. Concerning your point 4, I think I used remission in an unconventional way. I believe my doctor meant that all his patients who go into stem cell treatment having 5% cancer cells or less (but non zero) come out of the treatment with undetectable levels. On point 7, is there much understood on the mechanisms by which the cancer favors the osteoclasts? I may have read somewhere that bone is weakened because its calcium is diffused into a cancerous plasma more than into a non cancerous plasma. I could, however, have gotten something mixed up.

Dana, thanks for the tips. I went to your links and learned much about nonsecretory multiple myeloma. If I read your story correctly, you needed only about 2.5 months of primary chemo therapy before you reached remission, and it looks like it was complete remission. That seems like a relatively short time for primary therapy. I've been at it now for nine months, though I do think it's working me towards a stem cell procedure. I wish you well in your remission and I hope it's permanent.

[mikeb]

Re: New poster: story, and doubts about Zometa

by mikeb on Fri Dec 12, 2014 12:34 pm

Hi SBarro,

I want to follow up regarding what your doctor said about his success with stem cell trans­plants. While your doctor may thus far have a 100% success rate in getting patients down to undetectable levels of myeloma cells after the SCT, it is not uncommon for patients to still have some detectable level of myeloma left after the SCT. That was the case for me, for example. Also, while the goal might be to get the patient down to 5% before the SCT, that is not always the case. Sometimes you need to proceed with the SCT before getting to that level because the patient is not responding well enough to the pre-SCT treatment(s).

I just mention these points because I don't want you to have unrealistic expectations or feel like your SCT is a failure if you don't get down to 0% with the SCT.

In addition, what Dr. Hoffman said in his 3rd point is very important. Prolonged treatment can reduce the ability for your body to produce stem cells that are needed for the autologous transplant. I have a friend who had this happen to him. He was not able to produce enough stem cells for an autologous transplant and needed to have an allogenic (donor) transplant instead. Unfortunately, allogeneic transplants are riskier, and my friend ran into several complications. So I'd suggest talking with your doctor soon about beginning the stem cell collection process.

One final point / question - You are being treated by a myeloma specialist, rather than a general oncologist or hematologist / oncologist, aren't you? If not, it might be good to make an appointment with a myeloma specialist to at least review your treatment so far and future plans.

Best wishes, and please keep us posted on how things go.

Mike

[Mister Dana]

Re: New poster: story, and doubts about Zometa

by Mister Dana on Fri Dec 12, 2014 2:49 pm

Hello again SBarro,

Thanks for the well-wishes in your posting yesterday. You obviously did a lot of research about your treatments and SCT. I didn't know much about how Zometa works. I just read that it impaired the osteoclasts so the osteoblasts could catch up with their workload of laying down new bone tissue. I still don't know how my vertebral fracture healed and the pain went away; I kept my back brace just in case.

Going into SCT I had two troubling thoughts. First, I was opting for risk and discomfort to kill something that was no longer detectable. Second, I had a bizarre regret about killing off the marrow that had held up so well during my months of chemo. You, on the other hand, can proceed with a positive outlook about doing what is necessary. By the way, I calculated that the melphalan I got before my transplant was like getting three months worth of chemo in two days -- that is what they mean by an ablative dose. So when you have your SCT, you won't be cured, but you will be hitting that cancer with a hard blow.

Best of luck then, and between now and then!

Dana

[SBarro]

Re: New poster: story, and doubts about Zometa

by SBarro on Sat Dec 13, 2014 6:53 pm

Mike, my doctor is a hematologist/oncologist, and he considers himself a myeloma specialist. When he first recommended treatment, I asked him how many myeloma patients he had, and he said about 20, which I thought was a lot, especially since I had never heard about this disease before.

In my visit next week, I will definitely ask him about prolonged Revlimid primary treatment, as well as the criteria he recommends in going for the AuSCT. Thanks for your helpful concern.

Dana, thanks for your encouragement and good wishes. It's only recently that I've gotten up enough courage to read on the web about this serious disease. I was afraid that I'd focus too much on the negative things I'd see. But I see here that much helpful advice and en­courage­ment is available on this forum.

Tom

[SBarro]

Re: New poster: story, and doubts about Zometa

by SBarro on Sun Dec 21, 2014 11:03 am

Greetings,

Concerning Dr. Hoffman's Point 3 about extended Revlimid primary treatment making it more difficult to extract stem cells for an autologous stem cell transplant, I checked with my doctor, and he said that he wasn't aware of that. He is aware of other drugs causing such problems, but not with Revlimid. I will ask him if he has any further information for me when I see him tomorrow.

But I was wondering if anyone could elaborate on the reasons for that observation. Is it based on personal experiences, are there studies that indicate it, etc.? How serious is it? Is the harvesting just "a little more difficult," or is there the possibility of a failed procedure? In my own reading thus far, I found mention that Cytoxan [cyclophosphamide] and other drugs in extended primary treatment can cause such difficulties, but there's no mention of Revlimid.

Also, Mike, you mentioned that your friend had difficulty in harvesting stem cells because of "prolonged treatment." Do you know what drugs this treatment used? Was there a consensus among your friend's doctors that extended Revlimid was indeed the suspected cause?

As always, thanks again for your suggestions and for this wonderful forum.

Tom

[Melanie]

Re: New poster: story, and doubts about Zometa

by Melanie on Sun Dec 21, 2014 12:57 pm

Sbarro, we recently started seeing Dr. Jagannath at Mt. Sinai hospital in NYC and he also said that prolonged use of Revlimid can cause problems with collection of stem cells for the trans­plant. Dr. Jagannath is considered a myeloma specialist and we have met with him a few times already and I can see that he is much more knowledgeable than my husband's pre­vious doctor.

I am so thankful that his previous oncologist realized that my husband needed to see this doctor when his disease started to resist treatment. I think if you decide to go with a true specialist, you will truly see a big difference as I have seen already.

[JimNY]

Re: New poster: story, and doubts about Zometa

by JimNY on Sun Dec 21, 2014 5:09 pm

Welcome to the forum, Tom.

I've seen the doctors here in the forum regularly mention that initial therapy with Revlimid can create problems with stem cell mobilization. My impression from the postings is that there isn't necessarily a lot of concern if the initial therapy is going to be just 4, 5, or 6 cycles in length. But, these days, initial therapy can sometimes go on for much longer, and I think that's the sort of situation where the doctors start to get worried.

It's not like longer therapy with Revlimid is guaranteed to cause problems with mobilization, particularly now that mobilization can be helped with Mozobil. But doctors are always going to be nervous if they can't mobilize, say, 5 or 10 percent of the patients they'd like to mobilize. And the reality is that mobilization failures can happen, as demonstrated by the case of the person mikeb mentioned in his posting above.

The Beacon published an article last year that called Revlimid's potential negative impact on stem cell mobilization "conventional wisdom":

"Study Questions Conventional Wisdom On Revlimid And Stem Cell Collection," The Myeloma Beacon, May 3, 2013.

The article does cover, however, a study that suggests that the issue may not be as big a problem as had been thought.

The "conventional wisdom" is reflected in this International Myeloma Working Group (IMWG) consensus statement from 2009,

S Kumar et al, "Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens," Blood, Aug 27, 2009 (full-text pdf).

that states

Although there has been a wide spectrum of reported data on the initial therapy with a novel agent and the ability to collect stem cells, some common themes have emerged. In the 2 larger experiences published to date of lenalidomide therapy prior to harvest, the number of cycles of therapy appears to be important. Although none of the patients with fewer than 6 cycles of lenalidomide failed to collect stem cells in the Mayo Clinic series, more than 3 cycles of lenalidomide were associated with a higher risk in the M. D. Anderson series. However the smaller studies have not demonstrated such a relationship, and in the absence of detailed data from the larger prospective studies, it would be reasonable to assume that longer duration of therapy will increase the risk of failure."

The consensus statement goes on to make the following recommendation:

Given the potential for the novel agents to impact the ability of the stem cell collection, we recommend early stem cell mobilization when SCT is being contemplated immediately or later in the course of disease. Such an approach, after 3 to 4 cycles of initial therapy, is quite feasible given the rapid response seen with the new combinations."

You can find more on this topic by doing an Internet search on the keywords "lenalidomide mobilization".