[mrozdav]

BiRd therapy for IgA myeloma

by mrozdav on Tue Dec 16, 2014 11:10 am

I recently read a brief abstract coming from Japanese researchers (Kuroda, Jomen, et als; September 2014) in which it is asserted that clarithromycin (Biaxin) plus Revlimid plus dexamethasone is a highly effective treatment for newly symptomatic myeloma. The authors conclude that, in all cases, IgA levels decreased after switching to BiRd therapy ... and no toxicity was observed. It appears that they only had three cases, unfortunately.

Still, I am wondering what experiences IgA patients have had with this therapy.

A second question I have is whether there are myeloma patients who are given antibiotics as part of their induction therapy as a routine matter. Does anyone know whether there has been a Phase III clinical trial to evaluate the BiRd treatment? There seems to be little discussion of this therapy in the last two or three years although there was much manifested interest earlier on. (At least as far as I can tell.)

I am most interested in this topic because of a severe cough I have recently developed. A chest X-ray did not indicate a problem, but my doctor is suggesting a CT scan to rule out pneumonia or bronchitis. Clarithromycin is an antibiotic used to deal with both of these conditions, so I am wondering if adding it to the Revlimid and dex which I am taking anyway would not be effective to fight the cough and also to deal with the myeloma at the same time.

[JimNY]

Re: BiRd therapy for IgA myeloma

by JimNY on Mon Dec 22, 2014 4:06 pm

Hi mrozdav,

I'm not aware of any Phase 3 trial that has tested adding Biaxin in combination with other myeloma treatments. As far as I know, all of the studies investigating such combinations have been Phase 1 or Phase 2 studies, and most have been done by myeloma researchers in New York (usually with the involvement of Dr. Ruben Niesvizky from Weill-Cornell, who is probably the main proponent of Biaxin-based combinations).

There was a study at this year's ASH meeting that suggests that adding Biaxin to Revlimid combination regimens may improve the combination's efficacy by increasing the concentration of Revlimid in the patient's blood.

N Takezako et al, "Clarithromycin Elevates the Plasma Concentration of Lenalidomide Via Inhibition of MDR1," ASH 2014 abstract #3479 (link)

This matches what I've heard from some people who have talked to their doctors about this drug. The sense is that Biaxin mainly improves the response to the drugs it's combined with by effectively increasing the dose of the other drugs, rather than Biaxin having some independent anti-myeloma effect of its own. Of course, "effectively increasing the dose of the other drugs" means that you not only get increased responses to Biaxin-based combinations, but also increased side effects, including potential safety issues.

There was an interesting discussion a while back here in the forum about the possibility of another antibiotic, amoxicillin, having an anti-myeloma effect. There haven't been any updates,however, to that discussion in a while:

"Revlimid + amoxicillin, anyone?," Beacon forum discussion started Sep 13, 2013.

Good luck!

[JimNY]

Re: BiRd therapy for IgA myeloma

by JimNY on Mon Dec 22, 2014 4:12 pm

I forgot to add that, when I did a search for Beacon articles about Biaxin-based combination regimens for myeloma, I found that you can list all of them by using this link:

https://myelomabeacon.org/tag/biaxin/

As you'll see, the regimens almost always involve Biaxin combined with a regimen based on an immunomodulatory drug (thalidomide, Revlimid, Pomalyst). I remember reading once here in the forum that there are concerns about using Biaxin in combination with proteasome inhibitors, such as Velcade and Kyprolis, due to potential kidney issues. I believe it was Dr. Voorhees who mentioned this, or perhaps Dr. Shain, but I can't find the posting.

Hope that helps a bit more.

[SBarro]

Re: BiRd therapy for IgA myeloma

by SBarro on Tue Dec 23, 2014 12:34 pm

Mrozdav,

Concerning your question on antibiotics, I am now taking Bactrim (antibiotic, sulfamethoxazole and trimethoprim) and acyclovir (antiviral), as prophylactic. I take the Bactrim every Monday, Wednesday, and Friday, once per day, and the acyclovir every day, twice a day.

This is my second induction therapy session, planned to last three months, using RVD (Revlimid, Velcade, dexamethasone). In my first induction session, which lasted six months, using RVD plus Cytoxan (cyclophosphamide), I did not take those drugs, but rather received a Neupogen (filgrastim) injection 24 hours after my weekly treatment, which did a good job at keeping my white blood cell and neutrophils counts up.

My doctor explained that my immune system took quite a hit in that first session, so for this second session, which contains no Neupogen injection, the antibiotic and antiviral prophylactic will provide protection against a serious form of pneumonia, as well as herpes-related diseases, which can be quite uncomfortable. I also took my first flu shot.

I hope this helps, and I wish you good health.

Tom

[Dr. Jason Valent]

Re: BiRd therapy for IgA myeloma

by Dr. Jason Valent on Tue Dec 23, 2014 6:19 pm

I am not aware of a phase 3 trial of BiRd compared to another regimen (such as just Revlimid and dexamethasone alone). I did a literature search on this and did not find such a trial published.

The theory of using Biaxin in the treatment of myeloma is that it potentiates the effects of steroids and may have direct cytotoxic effect on myeloma cells.

In the original publication by Dr. Niesvizky (Blood 2008 Feb 1;111(3):1101-1109) (full-text) there were 16 patients with IgA disease although they did not comment on specific responses in the IgA patients.

Toxicity does not seem worse in Biaxin treated patients and response rates are quite favorable in the study of Niesvizky.