In the midst of the annual late May / early June medical conference season, with the many presentations of results from large-scale clin­i­cal trials, it is perhaps refreshing to learn that small-scale research has uncovered a pre­vi­ously unexplored poten­tial myeloma ther­apy.

In particular, physicians in New Zealand have found signs that roxi­thro­mycin, an antibiotic first used more than 30 years ago, may have anti-myeloma activity. The physicians shared their finding in a case report pub­lished last month.

In their report, the physicians describe the case of an 86-year-old man who has been under their care. The man was diag­nosed in June 2008 with IgA lambda smol­der­ing myeloma. Last August, after just a 10-day course of treat­ment with the antibiotic roxi­thro­mycin, the patient’s M-spike dropped sub­stan­tially.

Prior to the roxithromycin treat­ment, which was admin­istered to treat pneu­monia, the patient’s M-spike was 4.6 g/dL (46 g/l).

After treat­ment with roxithromycin, the patient’s M-spike was 2 g/dL (20 g/l), a de­crease of 57 per­cent.

Just as im­por­tantly, the reduction in the patient’s M-spike has persisted for the nine months since the roxithromycin treat­ment, according to data shared with The Myeloma Beacon by Dr. Ian Morison, one of the authors of the case report.

Similarly, the poten­tial anti-myeloma activity of roxithromycin was evi­denced not just by its impact on the patient’s M-spike, but also on his hemoglobin level.

Prior to treat­ment with the antibiotic, the patient’s hemoglobin level was 9.7 g/dL. After treat­ment, his hemoglobin reached 12.3 g/dL, and the elevation in hemoglobin level has persisted since last August.

Dr. Morison, who is a pro­fessor of pathology at the Dunedin School of Medicine in New Zealand, emphasized to The Beacon that the finding he and his colleagues have shared “is a single report of a single patient.” No conclusions should be drawn based on the report, he said, and not just because it con­cerns a single patient.

Dr. Morison and his colleagues have examined a few other cases of myeloma patients who were treated with roxithromycin, and “there were no other notable responses” to the antibiotic, he told The Beacon.  That having been said, Dr. Morison also noted that most of those other patients had pre­vi­ously been treated for their myeloma, making them less likely to respond to any treat­ment, in­­clud­ing roxithromycin.

In addi­tion, there is ex­peri­ence with another antibiotic similar to roxithromycin that suggests the finding the researchers share in their case report may be more than just an isolated anomaly.

Roxithromycin, Clarithromycin, And Other Macrolide Antibiotics

Roxithromycin belongs to the class of antibiotics known as macrolides. Several macro­lide antibiotics will be familiar to Beacon readers, in­­clud­ing azithromycin (Zithromax) and erythromycin. The macro­lide antibiotic of particular interest, how­ever, is clarithro­mycin (Biaxin).

Clarithromycin has been the subject of a number of myeloma-related research studies since the late 1990s, when a clin­i­cal trial found evi­dence the antibiotic might have anti-myeloma activity. Several studies soon there­after could not con­firm that clarithro­mycin by itself is active against myeloma. Later studies, how­ever, found that clarithro­mycin deepens treat­ment responses when the antibiotic is used in com­bi­na­tion with other myeloma ther­a­pies.

Many myeloma specialists attribute the deeper responses achieved when clarithromycin is com­bined with other ther­a­pies to be the result of clarithromycin prolonging the activity of the dexa­meth­a­sone that usually is in­cluded in com­bi­na­tion regi­mens. In essence, these specialists view adding clarithro­mycin to be equivalent to in­creas­ing the dose of dexa­meth­a­sone, a strategy that usually in­­creases treat­ment response, but does not always in­­crease over­all survival.

This is why clarithromycin is not used by many myeloma specialists as part of the treat­ment regi­mens they recommend.

There have been, how­ever, a number of specialists who have con­tinued to in­clude clarithro­mycin in treat­ment regi­mens they regularly use, the best known of which goes by the acronym “BiRD,” which stands for Biaxin (clarithromycin), Revlimid (lena­lido­mide), and dexa­meth­a­sone.

These clarithromycin proponents believe the antibiotic either has anti-myeloma activity on its own, or that its impact on the activity of com­bi­na­tion treat­ment regi­mens goes beyond just in­creas­ing the impact of the dexa­meth­a­sone in the regi­men.

Could Roxithromycin Be A More Effective Clarithromycin?

The reason all of this is relevant to the New Zealand roxithromycin case report is that roxithromycin not only is a close chemical rel­a­tive­ of clarithromycin, but it also is more easily absorbed into the blood than clarithro­mycin, and it stays in the body about 3 times longer than clarithromycin.

Both of these char­ac­ter­istics would make roxithromycin more effective against myeloma than clarithro­mycin even if, molecule for molecule, it was no more active against the disease than clarithromycin.

More About Roxithromycin And The Case Report

Roxithromycin is not approved for sale in either the United States or Canada, but it does have market­ing authori­za­tion in most European countries and many countries throughout the rest of the world, in­­clud­ing Japan, Korea, Australia, New Zealand, India, Israel, and South Africa.

Information about roxithromycin intended for patients and care­givers, and which is approved by New Zealand regu­la­tory author­i­ties, can be found in this “consumer medicine in­­for­ma­tion” leaflet. The New Zealand pre­scrib­ing in­­for­ma­tion for roxithromycin is avail­able here.

Dr. Morison and his colleagues are con­sidering organizing a clin­i­cal trial to assess the efficacy and safety of roxithromycin as a myeloma ther­apy. To get approval for such a trial, it would be helpful to have in­­for­ma­tion about addi­tional cases where myeloma appears to have responded to treat­ment with roxithromycin. If you are aware of such a case, please con­sider sharing in­­for­ma­tion about it with Dr. Morison. He can be reached via email at ian.morison@otago.ac.nz.

For addi­tional in­­for­ma­tion about the response to roxithromycin reported by the New Zealand physicians, see their case report, Chai, AY, et al., “Roxithromycin mono­therapy inducing a partial response in a patient with myeloma: a case report,” Journal of Medical Case Reports, May 10, 2018 (full text of article).