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 ^[1] (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.

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 ^[7] 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 ^[8] 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 ^[9], “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.”

Germany

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.

Spain

“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.

Italy

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 ^[10].  Patients or physicians who are interested in more information about how to receive or administer Velcade subcutaneously can call 1-866-Velcade (835-2233).