A case of spontaneous remission in smoldering myeloma

A blog reader (thank you!) sent me a remarkable study published in the “Journal of Clinical Oncology” (JCO) in October 2009. Unfortunately, there is no abstract (you won’t need it, though, since I will give you a summary of the study…uhm, just don’t tell anyone…shhh!). The title says it all: “Spontaneous Remission in a Patient With t(4;14) Translocation Multiple Myeloma.” Spontaneous REMISSION? Wow.

I had to look up the meaning of “t(4;14) translocation.” A 2007 study (see: http://tinyurl.com/ylqjves) informed me that patients with this translocation apparently have “reduced survival” and their myeloma is characterized by drug resistance and rapid relapse. It does not respond well to conventional chemotherapy. (More details are available in the full study, available for free online at the link provided.)

Okay, now back to the JCO study. In December 2005, a 60-year-old woman with high ESR (121 mm/h!) and low Hb (113 g/L) was diagnosed with asymptomatic, or smoldering, myeloma. More precisely: Durie-Salmon stage 1A/International Staging System stage I multiple myeloma.

At that time, her IgA (kappa) was 30,3 g/L, her bone marrow had 20-30% of the evil cells, and skeletal x-rays revealed osteopenia (that means lower than normal bone density) and “multiple subtle lucencies.” Her creatinine was slightly elevated, but the rest of her markers, unless I missed something, fell into the normal range. I noticed that her B2M was right on the high end of normal, though. And then, of course, there was this business of the above-mentioned t(4,14) translocation.

I was puzzled by her SMM diagnosis, actually, given the t(4,14) translocation and the “subtle lucencies.” That doesn’t sound like asymptomatic myeloma to me, but of course I am not an MD. Well, let’s go on.

There follows a series of technical terms that I do not fully comprehend…just to give you an example: tests revealed the presence of a hyperdiploid karyotype with trisomies of chromosomes 3, 4, 9, 18, and 19, and monosomy 13, as well as a focal deletion on chromosome X containing […] three genes that have been implicated in the pathogenesis of cancer. I don’t have the time to look up this stuff right now, so I will simply have to ignore it.

She was treated only with monthly intravenous infusions of pamidronate. Incredibly, her M-protein began declining. In December 2005, her IgA was 30,3 g/L; in June 2006 it had decreased to 2,23 (!). At that time no paraprotein could be detected by immunofixation. A BMB revealed the presence of a mere 5% neoplastic cells, and her blood tests, freelite included, were all normal. Her skeletal survey remains unchanged.

More details (doing a bit of copy and paste here, to make things clearer). The authors inform us that their patient was also diagnosed with type I cryoglobulinemia IgA-kappa. Cryoglobulinemia refers to the presence of immunoglobulins in serum that precipitate at cold temperatures. In fact, one of my dearest blog readers has this type of problem. In winter he has to stay mostly indoors.

Her type I cryoglobulinemia IgA-kappa was diagnosed in 1985 when she presented with arthritis, purpura, and Raynaud’s phenomenon. Cryocrit had ranged from 0%to 25% over the years and most recently was 5%. She did not require treatment until 1989, when she was placed on low-dose prednisone 5 to 7.5 mg/d.

After almost four years, the woman is still in complete remission. The authors say that they have documented spontaneous remission (SR) in a patient with IgA-kappa MM only receiving pamidronate and intermittent low-dose prednisone. SR of cancer is defined as a complete or partial, temporary or permanent disappearance of all or at least some parameters of a soundly diagnosed malignant disease without any medical treatment or with treatment that is considered inadequate to produce the resulting regression. This is an extremely rare event with a reported incidence of less than one in 60,000 to 100,000 people with cancer.

To the authors’ knowledge, there is only one other documented case of SR in myeloma, a 68-year-old man with multiple lytic lesions and nonsecretory myeloma. His case, briefly: after having surgery on his spine, he developed a a Staphylococcus aureus infection. After 10 cycles of chemotherapy with vincristine, cyclophosphamide, melphalan, and prednisone/vincristine, carmustine, doxorubicin, and prednisone, García-Rayo et al documented complete radiological resolution of the bone lesions precipitating the diagnosis and absence of plasma cells in a repeat bone marrow biopsy. This was interpreted as a case of SR in the context of infection. Infection…interesting, huh?

The researchers point out that nitrogen-containing bisphosphonates can have antitumor effect in human myeloma cells in vitro. But the results from murine models have been contradictory. Based on the literature, there seem to be only four cases suggesting antimyeloma effects of bisphosphonates, specifically pamidronate.

The study concludes: Recently, it has been discovered that nitrogen-containing bisphosphonates such as pamidronate can stimulate human gamma delta T-cells, both in vivo and in vitro. We speculate that the cytolytic activity against MM cells exerted by gamma delta T-cells stimulated by pamidronate could be one of the mechanisms responsible for the SR of our patient, as we were not able to demonstrate direct antitumor activity of pamidronate against cells lines or primary patient samples in vitro (results not shown).

What to conclude from this? The authors don’t know for sure, and I certainly am not going to start having pamidronate infusions (=side effects can be really nasty). But I would be curious to know if any readers have derived benefits from pamidronate. Please drop me a line or, better yet, leave a comment here if you have. Thanks!


  1. My oncologist has repeatedly told me that Zometa given IV has an anti-myeloma efffect as well as helping heal bone lesions. I have no way of checking this as I have had other treatments and supplements as well as 4 years of monthly IV Zometa – have been off it for 1 year (my choice). I was diagnosed in 2001 with myeloma and am currently asymptomatic. Still have an mspike of 1.1

  2. Hi Margaret — “a hyperdiploid karyotype with trisomies of chromosomes 3, 4, 9, 18, and 19, and monosomy 13, as well as a focal deletion on chromosome X containing.”…normally we have 23 pairs of chromosomes (a normal karyotype) but sometimes as in Down’s syndrome there are three meaning trisomy –this of course increases the number of chromosomes and if it surpasses 50 it is called “hyperdiploid” .. a deletion refers to a part of chromosome missing.

    I gather a certain percentage of MM patients have chromosomal abnormalities especially #13, 17 and this means a poorer prognosis.

    I agree that this woman sounded more like true MM rather than smouldering but of course it’s great she is doing better –I think there are spontaneous remissions in all cancers from time to time. Gerry

  3. Spontaneous regression of lymphoma or plasma cell dyscrasia is often of substantial duration, months or years, and frequently is associated with viral infections.

  4. Dear Margaret et al,

    I have been getting pamidronate monthly since my first (7)chemo cycles a year ago. I have full-blown IgA-kappaLC MM, and my initial remission didn’t last more than a few months (with attempted maintenance only with Revlamid, discontinued due to low blood counts – and monthly pamidronate, all along since the first chemo regimen began). I’ve got a billion stem cells collected and am loathe to transplant them (yet) – as are my oncologists.

    This past week, I just began a second chemo cycle, also including monthly pamidronate – with once-weekly Velcade now (instead of twice).

    I have never noticed any side effects from the pamidronate before. However, I was temporarily dizzy last night and this morning, beginning several hours after yesterday’s infusion, which was topped with Velcade as well – and the first 15 mg Revlamid dose for this chemo cycle…

    Dizziness is indeed listed as a pamidronate side effect (among a huge number of other ones), e.g., at: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601163.html#side-effects. Has anyone else here ever noticed this particular side-effect?

    Any other comments about my treatment regimen among the blog denizens?


    Dave (;^}

  5. Hi Margaret, and other readers,

    I got my MM diagnosis (stage 1) five years ago. More recently I thought that my MM was considered indolent because of very little variation in lab results over time, and infact, there was improvement in the M-spike being less. Anyway, I thought I was still smoldering or very indolent as my physician put it, but I found out that the medical codes used for billing and reimbursement between the cancer center I used to go to for lab & radiographic testing for the “watchful waiting” protocol indicate they coded my MM as Multiple Myeloma in remission.

    2012 ICD-9-CM Diagnosis Code 203.01
    So, I am in remissionI without having had any treatment. Is the dome kind of miracle or is it a matter inappropriate measurements being used to come with a meaningful diagnosis.

    I’m confused! Happy but confused.


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