[Cheryl G]

IV Velcade after subcutaneous Velcade

by Cheryl G on Mon Mar 14, 2016 12:02 pm

Hello everyone,

Another interesting study came out lately that I thought I'd share. The full text of the study is available for everyone to read, and it's not very long.

The study concerns treatment with intravenous Velcade after a patient has stopped responding to subcutaneous Velcade. It's a single-center study from a hospital in Italy, and it's also a retrospective study.

The authors looked at all the patients at their hospital who had been treated with subcutaneous Velcade from January 2013 to May 2015. This was a total of 91 patients. Of those 91, 17 patients were given intravenous Velcade when they stopped responding to the subcutaneous Velcade.

Here is where it gets interesting. Of the 17 patients who got "rescue IV Velcade", 12 (71%) responded to the treatment. The response did not last long -- only a matter of a few months. But there was a response, with M-spikes dropping about 40 percent in the 12 patients who responded to the IV Velcade

The authors describe more details of what they found (remember: bortezomib is the generic name for Velcade):

Twelve of the 17 patients showed a transitory M component re­duction. A re­sponse was seen soon after the first cycle in the patients that responded. Median mono­clonal component [M-spike] reduction was 41% from baseline (range 18–89%). Responders received IV bortezomib until pro­gression, with a median response period of 2 months (range 1–7). Toxicity did not increase after switching to bortezomib IV. The patient that achieved a more durable re­sponse had previously received bortezomib IV. The other patients achieving transitory re­sponses were previously treated with a median of 3 lines of therapy (2–6); 6 were bortezomib-naive at SC administration. The addition of a third drug (melphalan-cyclo­phos­phamide) did not recover response at disease progression.

Here's a link to the study if you want to read more about it:

A Gozzetti et al, "Intravenous (IV) bortezomib infusion after non-response to sub­cu­tane­ous bortezomib administration can induce transitory responses in multiple myeloma patients: are some patients more sensitive to IV bortezomib?", British Journal of Haematology, March 2016 (full text of article)

[dogmom]

Re: IV Velcade after subcutaneous Velcade

by dogmom on Mon Mar 14, 2016 2:38 pm

My husband's myeloma specialist has always given his induction therapy of cyclo­phos­phamide, Velcade, dexa­metha­sone(CyBorD) with IV Velcade instead of injection.

[JimNY]

Re: IV Velcade after subcutaneous Velcade

by JimNY on Mon Mar 14, 2016 3:50 pm

Thanks, Cheryl. That's an interesting study. It reminds me of the study covered in this Beacon article from last year:

"Subcutaneous Velcade Leads To Similar Response Rates, But Fewer Side Effects, Compared To IV Velcade In Newly Diagnosed Multiple Myeloma," The Myeloma Beacon, April 20, 2015

It discusses a study that found that intravenous Velcade and subcutaneous Velcade give similar response rates. However, intravenous Velcade tends to give you deeper responses than subcutaneous Velcade.

[Multibilly]

Re: IV Velcade after subcutaneous Velcade

by Multibilly on Mon Mar 14, 2016 6:19 pm

You wonder if one could achieve the same kind of a rescue response by simply increasing the subcutaneous Velcade dose? And would doing that still result in less peripheral neuropathy than what might be experienced with IV Velcade at the normal IV dose level?

[Cheryl G]

Re: IV Velcade after subcutaneous Velcade

by Cheryl G on Mon Mar 14, 2016 10:11 pm

Thanks for your comment, Jim. I agree -- the two studies are related. The authors of the new study actually refer to the study summarized in the Beacon article, writing

"Interestingly, a recent German Myeloma Group study (Merz et al, 2015) compared the IV versus the SC route retrospectively for VCD and PAD induction therapy in newly diagnosed multiple myeloma patients. The analysis of high quality responses revealed that IV-treated patients achieved higher rates of ≥very good partial response than SC-treated patients (42% vs. 29%, P = 0·02) after 3 cycles of therapy."

Multibilly - You ask a really good question. In fact, it sparked me to poke around a bit to see if I might be able to find anything that might say whether or not your suggestion would work.

What I found is a study that looks at how the concentration of Velcade in the blood is similar, and also how it is different, when the drug is given intravenously and subcutaneously. Here is the study:

P Moreau et al, "Pharmacokinetic, Pharmacodynamic and Covariate Analysis of Subcutaneous Versus Intravenous Administration of Bortezomib in Patients with Relapsed Multiple Myeloma" Clinical Pharmacokinetics, Dec 2012 (abstract)

What the authors of this study found is that the two methods of Velcade administration expose patients to the same amount of the drug. When you plot a curve showing the concentration of Velcade in a patient's blood, the total area under that curve is the same for IV and subcutaneous Velcade administration. This means that the total drug exposure is the same.

The difference between the two methods, however, is that giving the drug by IV leads to a much higher peak concentration of Velcade in the blood. The peak concentration with IV admin­istra­tion is about 10 times as high.

The higher peak concentration with IV administration may explain how it achieves both deeper responses and why it can "rescue" some patients. If that is true, then it also means – un­fortunately – that just increasing the dose of subcutaneous Velcade might not have the same "rescue" effect as giving the drug by IV.

But it would be worth testing the idea sometime!