November 14 2009 post. 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!