Subcutaneous Velcade: Information For Multiple Myeloma Patients

by and
Published: Sep 2, 2011 12:14 pm
Subcutaneous Velcade: Information For Multiple Myeloma Patients

Multiple myeloma patients being treated with Velcade often experience peripheral neuropathy, which is nerve damage that causes pain, numb­ness, or tingling in the extremities.  Recent studies have identified two ways of reducing neuropathy and other side effects associated with Velcade, while maintaining similar efficacy: administering Velcade intravenously once weekly instead of twice weekly or administering Velcade subcutaneously instead of intravenously.

Velcade (bortezomib) is currently approved to be used intravenously for the treatment of multiple myeloma in the United States and over 90 countries worldwide.  Approximately 30 percent of multiple myeloma patients who take intravenous Velcade experience peripheral neuropathy.  Velcade may also cause low levels of red blood cells, white blood cells, and platelets as well as gastro­intestinal problems such as nausea, vomiting, diarrhea, and constipation.


News articles about:
- subcutaneous Velcade
- peripheral neuropathy
- Velcade

Forum discussions about:

- subcutaneous Velcade

- peripheral neuropathy

- Velcade

Physicians regularly decrease dosages or frequency of administration of drugs to manage side effects, so weekly administration of Velcade has already become commonly used since the study demonstrating its safety and efficacy.

However, subcutaneous administration, commonly abbreviated as subcu or subQ, is being used to a more limited extent for Velcade, since it is not yet officially approved for use in any country. Patients interested in receiving Velcade subcutaneously may need to request the new route of administration or specifically seek treatment at a center that is currently using the subcutaneous method.

Recent Findings About Reducing Velcade Side Effects

Results from an Italian study showed that reducing the dosing frequency of intravenous Velcade from twice weekly to once weekly significantly reduced side effects, including peripheral neuropathy (see related Beacon news).

In addition, results from a French study presented at the American Society of Hematology meeting in December showed that administering Velcade subcutaneously (injected into the fat just below the skin) also reduced side effects (see related Beacon news).

The study of subcutaneous Velcade included 222 multiple myeloma patients who were randomly assigned to receive either intravenous or subcutaneous Velcade.

The overall response rates, median times to progression, and one-year survival rates were similar for patients receiving intravenous Velcade and those receiving subcutaneous Velcade.

The frequency of severe and life-threatening side effects, however, was significantly lower for patients who received subcutaneous Velcade (57 percent) as compared to intravenous Velcade (70 percent).  More specifically, patients who received subcutaneous Velcade had a significantly lower rate of severe peripheral neuropathy (6 percent) than patients who received intravenous Velcade (16 percent).

Based on these findings, Millennium, the company that markets Velcade in the U.S., submitted an application to the U.S. Food and Drug Administration (FDA) for the approval of subcutaneous Velcade. The company expects an FDA decision on the application by January 23, 2012.

Although it may become possible for patients to administer subcutaneous Velcade in their own homes, a representative from Millennium said that the company is currently focusing its efforts on subcutaneous administration of Velcade by health care professionals.

There have not yet been any studies combining weekly and subcutaneous administration of Velcade to see if the combination further reduces side effects while maintaining efficacy.  The Millennium representative could not comment on whether the company has any plans to study this combination.

Current Use Of Subcutaneous Velcade In The U.S.

Although the FDA has yet to approve subcutaneous administration of Velcade, physicians at a number of treatment centers across the U.S. have already been giving Velcade subcutaneously to myeloma patients.

As Dr. David Vesole from the John Theurer Cancer Center in Hackensack, New Jersey, wrote in his latest Beacon column, “We have incorporated the subcutaneous administration of Velcade for all of our patients.  Only a single patient has requested to be converted back to intravenous administration due to localized rash at the injection site.”

Dr. Ken Shain from the Moffitt Cancer Center in Tampa, Florida, also told The Myeloma Beacon, “I have incorporated subcutaneous Velcade into about 8 percent to 10 percent of my relapsed and refractory patients.”

“In our experiences to date, no patient has had significant issues with subcutaneous Velcade—no site reactions [such as rashes] or need to return to intravenous dosing.  Nor have I yet to have a patient who would rather have intravenous than subcutaneous [Velcade],” he added.

Although Dr. Shain is “very enthusiastic” about the potential of subcutaneous Velcade, he believes that subcutaneous Velcade needs to be studied further before it will become widely adopted.

“I am not ready to declare a new standard of care [with subcutaneous Velcade], and I do not recommend it for all patients.  However, it is a realistic option for individuals with pre-existing neuropathy,” he stated.  “The community infusion centers thus far have not moved in this direction and remain hesitant in my experience.”

Dr. Mario Curti, a hematologist whose group practice in Los Alamitos, California, includes an infusion center for myeloma patients, said that he currently does not administer subcutaneous Velcade to his patients because of reimbursement issues caused by subcutaneous Velcade not yet being officially approved.

However, he stated to The Myeloma Beacon that he would begin to give subcutaneous Velcade to his patients once it becomes approved by the FDA.  According to Dr. Curti, “[Subcutaneous Velcade] will be more convenient [than intravenous Velcade] and just as effective.”

Current Use Of Subcutaneous Velcade In Europe

As in the U.S., subcutaneous Velcade is not yet approved by the European Medicines Agency, the regulatory agency that approves treatments for use in Europe.  However, as in the U.S., treatment centers in some European countries are currently giving subcutaneous Velcade to myeloma patients, even though it has not officially been approved for use.

United Kingdom

According to Dr. Faith Davies from the Institute of Cancer Research and the Royal Marsden Hospital in London, both subcutaneous as well as weekly Velcade are being used in the U.K.

“Following the publication of the subcutaneous data, hospitals are putting the new route of administration through their hospital Drugs and Therapeutics Committees to get approval to switch delivery method,” said Dr. Davies.  She indicated, however, that some hospitals may require official approval of the subcutaneous route of administration before it can be used.

“From a patient’s perspective, [subcutaneous administration] will hopefully make delivery a more pleasant experience (no need for intravenous access, no need for hydration, quicker delivery, and fewer side effects),” she added.  “Importantly, hopefully the neuropathy side effects will be decreased, enabling patients to tolerate the drug longer and thus benefit from better and longer remissions.”


Dr. Hermann Einsele of the Würzburg University Medical Center told The Myeloma Beacon that he also uses subcutaneous Velcade for some of his myeloma patients and weekly administration for others.

“We are offering subcutaneous Velcade and feel that indeed the rate of peripheral neuropathy is reduced [in patients who receive it],” he said.

“We feel that [subcutaneous Velcade] might completely replace intravenous Velcade if peripheral neuropathy can be significantly reduced,” he added.

It is not clear, however, how many physicians are using subcutaneous Velcade throughout the rest of Germany.


“I think there are a lot of hospitals in Spain prescribing the subcutaneous formulation of Velcade,” said Dr. María-Victoria Mateos from the University Hospital of Salamanca. Both she and Dr. Joan Bladé from the Hospital Clinic in Barcelona, however, said that their hospitals are not using subcutaneous Velcade.

Dr. Mateos added, “[Subcutaneous] treatment with Velcade will be more comfortable for the patients, easier for the nurses, require less time at the outpatient facilities, and finally, in the near future, it will be possible for home administration.”  She also said that Velcade will be used more often as maintenance therapy, particularly once it is available for home administration.


Dr. Michele Cavo from the Seràgnoli Institute of Hematology and Medical Oncology in Bologna said that in Italy, Velcade is being given weekly to reduce side effects, but subcutaneous administration is not being used, since it is not yet approved in Europe.

He also said that once subcutaneous Velcade is widely used, more patients are likely to be treated with Velcade and it is more likely to be used as maintenance therapy “even though the proof of clinical benefit from Velcade as maintenance therapy is still lacking.”

Patient Experience With Subcutaneous Velcade

Five years ago, Melanie Kuftic’s mother was diagnosed with multiple myeloma at the age of 59. From March through May 2011, she used subcutaneous Velcade, before changing to a different treatment regimen.

Velcade was not being administered subcutaneously at the time at VCU Massey Cancer Center in Richmond, Virginia, where she was being treated, but when Kuftic’s mother requested subcutaneous administration, her oncologist was very supportive.  The nurses at the center were trained how to administer Velcade subcutaneously, and she was the first patient at the center to begin receiving Velcade by the new route.

“The oncology nurse would inject the Velcade in my mom’s stomach area about 2 inches away from her belly button, alternating sides for each week’s injection,” described Kuftic.

“Her side effects were considerably improved switching from intravenous to subcutaneous – significantly less neuropathy, diarrhea, and cognitive impairment,” Kuftic explained.

“She did not have any worse side effects from the subcutaneous Velcade, but she did get a red rash-type of reaction around the injection site, which was about the size of a quarter to half-dollar and would fade into a light bruise and disappear in about a week.  It didn’t itch or hurt unless direct pressure was applied to the area.”

For more information about patients’ experiences with subcutaneous Velcade, see the related discussion in the Beacon’s multiple myeloma forums.  Patients or physicians who are interested in more information about how to receive or administer Velcade subcutaneously can call 1-866-Velcade (835-2233).

Photo by stevendepolo on Flickr – some rights reserved.
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  • TerryH said:

    I think I know the answer to this question, but I just want to double check. If you get Vecade subcutaneously, you are getting exactly the same thing as someone who gets Velcade intravenously, right?

    In other words, subcutaneous Velcade isn't some different version of Velcade, that a doctor has to special order from Millennium or from a distributor. It's just the same Velcade, given differently.

    I don't mean to be a stickler for details. I just want to make sure I'm absolutely clear on the issue. If it's exactly the same as intravenous Velcade, then it seems to me that it should be easy to get subcutaneous Velcade just about anyplace.

    Thanks for a very helpful article!

  • Jan Stafl MD said:

    Although sq Velcade twice weekly is more convenient than once weekly IV, with equivalent benefit, a unique side effect with the sq administration is a local reaction. After three doses sq, my cellulitis on my lower abdomen became increasingly pruritic and erythematous (itchy and red), causing me to abandon the sq route of administration. The IV form, preceeded by 40 mg of IV Dexamethasone, seems to be better tolerated in my case.
    Five weeks after starting chemo with Velcade and po Revlimid, my local reaction from sq Velcade is still visible in all three sq sites, although it is slowly fading. It is worth it, though, since my labs have already normalized, and I'm hoping that I will be in complete remission after my initial 12 week course of therapy.
    By the way, as an OB\GYN physician, this challenge and opportunity of healing Multiple Myeloma has been an extraordinary experience. Being a patient and a doctor allows me to experience it from both sides. Already many blessings and much love have come my way from my family, friends and colleagues. I have chosen to approach this dark invitation holistically, which is the way I practice medicine. This means I use a number of supplements, including curcumin, acupuncture, bioenergy, Jungian psychotherapy, and meditation. I don't know yet if I can permanently cure this disease, but I know I can heal on many levels. Best wishes to all with this challenge!

  • Gary said:

    For those of us on Lovenox the thought of another injection in the stomach is not appealing!

  • Christine Rice said:

    I would bet there is a big difference between the subq administration of Lovenox and Velcade as the frequency of dosing would not nearly be as often as Lovenox which has to be given daily or sometimes twice daily.

  • mike dent said:

    Does anyone know if subq velcade can be injected into a port instead of directly into the skin? I look for any reason not to receive shots in the skin, particularly since this is a lifelong disease and the impacts of years of injections will take a toll.

  • Julie Zimmer said:

    impact of getting veins poked is another reason to go SQ - veins harden and roll after being frequently penetrated. "My" patient gets sub Q once weekly. Initially it was IV once weekly because two trips in the car were hard on his vertebral compression fractures and spinal fusion. So he just stuck with the 1X week when I talked the Dr. into trying subQ. I used a copy of a Beacon article last season to persuade the Dr. Now ALL the MM patients in that office get it subQ.
    it doesn't feel as difficult as doing lovenox every day felt - and the patient did Lovenox himself, he would not have been happy with a family member doing it.
    Insurance pays for it, no problem. It is to their advantage if he has less neuropathy and fewer invasive interventions. Had a port briefly for dialysis, THAT was invasive - had to be very careful to avoid infection - difficult to shower/bathe. Had a rash the first 2 times subQ. Not sure if this helped, but the tech started injecting at an angle and pushing more slowly. No rash since then.

  • Al said:

    mike, doesn't injecting something into a port automatically make it intravenous? I don't think injecting it into the port would lessen side effects like subQ injections. Maybe you should ask your doctor about reducing the frequency of injections to weekly using your port.

  • ann said:

    can anyone tell me the reconstitution ratios for the subQ doses of velcade? my spouses chemo pharmacy is freaking because his md ordered his velcade subQ. 1st week refused to follow order, administered via his port (causes whole laundry list of side effects); 2nd week gave him iv dose subq (nearly 2ccs) because they had already mixed to give via port and cost prohibitive to start over; yesterday, velcade came up from pharmacy to be administered via port (2ccs worth then 2nd dose sent up was less than .5 ccs) i am afraid for my spouse and want to have my chickens ready for the broiler when i fly in on them today. help! up all night worrying whether they are going to kill my hubbie because they are resistant to a good thing.

  • Myeloma Beacon Staff said:

    Ann - Millennium, the company that markets Velcade, recommended that any patients or treatment centers with questions about how to prepare or administer subcutaneous Velcade should call 1-866-Velcade (835-2233).

    TerryH - You're correct that subcutaneous Velcade is the exact same drug as intravenous Velcade. As Ann describes above, the Velcade powder can be reconstituted (dissolved) in a different amount of liquid depending on whether it is going to be injected into a vein or the skin. The same amount of powdered drug with a smaller volume of liquid is generally used for subcutaneous injections.

  • Patrisha Thom said:

    I just read all the postings on Sub Q Velcade and was glad to see the mostly positive input. I was diagnosed with MM 8 weeks ago and am currently on my "third round" of Sub Q Velcade, with Dex (5 pills) before each injection. I would say that it is going well for my situation, the only localized reaction is a red area that usually is the size of a 'quarter', sometimes gets a little warm feeling..but generally goes away within the week. The Oncology nurses alternate sides for each shot..and are saavy now to go in sideways and slow...much less noticeable (for someone not fond of needles, but getting used to it!) By the way, I am the first in the clinic to have this delivery and thankful that my doctor picked me! Perph. Neuropathy becomes slighly apparent with each successive injection (4 in two weeks)..but I am taking Vit. b-6 slow release tabs (200 mg) and rubbing Palmer's Cocoa Butter into my feet before bed and I do believe these are working to minimize any discomfort.

    Good luck to all of you trying to beat this disease, as I am learning how to cope with this unexpected diagnosis. Finding these websites devoted strictly to MM have been a blessing.


  • T Lee said:

    For all those folks who have been receiving the Sub Q Velcade, is their insurance covering it even though it is not FDA approved? My Husband is about to receive this and we have already fought many insurance problems to date so do not want another. We appreciate your immediate feedback. Thanks

  • Ricardo said:

    I don't have direct experience with subq Velcade, T Lee, but I don't think reimbursement will be an issue. You are getting the same amount of Velcade as you would get if it were infused. It's just being administered differently. In fact, it's probably slightly less expensive for the insurance company to cover subq Velcade, because the company won't have to pay the doctor's office for the time your husband would have been in the infusion chair.

    This page at the Velcade website may have more information, and telephone numbers you can call, that might be helpful:

    I agree that it would be useful to hear from others who may have received subcutaneous Velcade and what sort of issues they may have had, if any, with reimbursement.

    Good luck ... and please let us know what you find out!

  • Beacon Staff said:

    T Lee ... You also may find the discussion in this thread in the Beacon's forum useful:

    One or two people said in that thread that they haven't had reimbursement issues when receiving subcutaneous Velcade.

  • Celinda Lovett said:

    Anemia, low WBC, Fatique. I was Dx. Aug 16m2011. Recieving my third cyccle of IV V/D. Mild neuropathy. Has the Subq administration of Velcade reduced or help any of the aforementioned symptoms?

  • Linda said:

    How long does naropathy last, does it ever go away even though i am taking the Velcade sq?

  • Lois Summers said:

    Have just completed my 12 treatments with Velcade and Dexadron, with a Zometa(sp?)infusio once monthly for bone strength. I will continue the Zometa infusions monthly. Velcade was give sq on the back of my arms. Short sleeves did expose the red patch, but the thought of injections in my stomach is not appealing at all. I had no neurothapy with the sq.

    I am a Medicare patient with an Anthem Blue Cross supplement policy and have had no problem with coverage.

    Good luck to all.

  • Mike Marrella said:

    I have been receiving Velcade biweekly for about 2 years now, and in the past 3 months, through the subcutaneous route. This was a welcome respite from the IV course despite the rather marked local reaction on the site for about a week's time. However, over the past 3-4 weeks there has been a generalized rash over different parts of my body which can be quite itchy and disturbs sleep induction. I've eliminated several supplements which were thought to be the possible culprits, but it's still present and possibly getting worse. Has anyone heard of a similar reaction, if it is the Velcade?

  • Tina H. said:

    I just started treatment and have had 2 weekly subq injections. The facility I go to only gives the treatment that way, according to my dr. and nurses. I am thrilled. I was caught early and have only had sporatic carpal tunnel-type issues in my hands, which has actually lessened this past week. At night, if I sleep on my side, my arm would go numb quickly. No issues this week at all.
    No feet tingling. Both injections produced a reddening at the site, w/o any itching or pain. I had read the advice of going in at an angle and going deep all the way through the shot. I didn't bring it up because I had a different nurse the second time and was curious if it was how the first nurse administered the shot. She started slow and then went deep, causing me to say ouch. The second time, I noticed the nurse go in at an angle, though she only went in 2 inches below the first site, which has changed from red to light brown but not gone away. I didn't feel any pain and the red spot came up bigger than the first, though with no pain. The size variation went from 1.25" dia. from the 1st shot to 2"x1.5" dia for the 2nd. I guess I'll ask them to switch sides next Friday and go at an angle and go slow but deep.
    Maybe I'll say ouch a few times.
    Overall, after 2 weeks, I can't complain about the minimal side effects, unpleasant, but infinitely better than the alternative. Good luck to all.

  • Ricardo said:

    A few bits of advice and information about subcutaneous Velcade that I've picked up from reading about the subject ...

    First, if you're going to get it, make sure it is diluted properly. If it is not diluted enough, you are much more likely to have injection site reactions. I believe the proper dilution ratio is 2.5:1.

    Second, if you get redness or swelling around the injection site, some people say this can be prevented or reduced by putting an ice pack on the injection site for a while after the injection.

    Third, there is a good discussion in the Beacon forums, in the coverage of the ASH meeting, about why subcutaneous Velcade seems to have fewer side effects than IV Velcade. This is the posting:

    The part that is relevant is the part discussing this poster that was presented at the ASH meeting:

  • TerryH said:

    There's an interesting story behind why subcutaneous Velcade even started being used. The CEO of Millennium recently said that the whole reason the company got interested in subcutaneous Velcade is because a nurse in France had a patient whose veins were so thin they couldn't easily accept infused Velcade. So the nurse and the patient's physician decided to see if subcutaneous Velcade would work just as well.

    And it did, and they tried it on some more patients, and it continued to work well, and Millennium heard about the results and decided to explore the issue further.

    And the rest is history!

  • Gayle Masserant said:

    Hello to everyone!
    I was treated three years ago with the twice weekly injections of Velcade.. Killed my feet but even though I can no longer feel them, I can still walk on them. I am a greater fall risk. I am now on the sub-q and getting a red wheal and itchy bumps. I realize this is normal for some and will not cause me to stop the drug. It put me into remission before my stem cell transplant in two months so I hope it will work this well this time! I need to have total hip so am hoping for a quick remission. My best to all of you! Gayle

  • anil shah said:

    My wife has taken 14 IV injections of bortizomib twice a week and complted treatment on 17 th june 2011.
    Even after 7 months of takiing medicene and vitamin -Methy cobol 500 mcg-twice daily ahe is still suffering for acute peripheral neuropathy.
    Please advise remedy. Thanks.
    Anil shah

  • David Hynes said:

    I've been receiving sq Velcade on 7 th week. Got some injection site rashes larger than a silver dollar. To correct this nurse does not force Velcade into tip of needle so that a little air might get in but velcade on needle is an irritant, she also injects very slowly ( count of 10) so I don't get the burning sensation during injection, when withdrawing careful not to bring velcade back,and less alcohol swab after.This has reduced the blotch to a small pimple size to almost undetectable. Thanks David

  • Robert LaBrode said:

    I have been getting Velcade injections in the stomach for a month now. I find it stings for a bit and also get stomach rashes. They do go away and are not annoying. Better then before hated the numinous in the fingers. Will start stem cell harvest and transplant in August.