Treating Multiple Myeloma Patients: Optimizing Response While Minimizing Side Effects
Novel agents, such as Velcade (bortezomib) and Revlimid (lenalidomide), have greatly advanced the treatment of patients with multiple myeloma. Indeed, by incorporating novel agents as induction therapy prior to consolidation with high-dose therapy and autologous stem cell transplantation, we have made huge strides in survival outcomes over the last 10 years. However, treatment with anti-myeloma agents may be associated with side effects that negatively impact quality of life.
Recently, two advances have been reported resulting in a decrease in peripheral neuropathy (nerve damage causing pain, numbness, and/or tingling in the extremities) for patients receiving Velcade.
A report by the Italian group compared once weekly Velcade with twice weekly Velcade. They observed similar response rates and survival between the two groups – predominantly because the twice weekly group had dose reductions or discontinued therapy due to side effects that were not nearly as evident with the once weekly schedule (15 percent versus 5 percent). Further, more severe peripheral neuropathy was reduced from 28 percent to 8 percent. (See related Beacon news for more information.)
In a second trial reported by the French Myeloma Intergroup, they utilized subcutaneous Velcade injections (just under the skin) rather than the standard intravenous infusions. Again, response rates and duration of response were virtually identical between the two methods of Velcade administration. However, side effects were significantly less apparent in the group of patients administered subcutaneous Velcade: moderate neuropathy decreased from 41 percent to 24 percent and severe neuropathy from 16 percent to 6 percent. (See related Beacon news for more information.)
In the Myeloma Division at The John Theurer Cancer Center at Hackensack University Medical Center, 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. Whereas most patients continue to receive twice weekly Velcade, a number of our patients are treated with once weekly Velcade depending upon the individual patient’s clinical status.
Revlimid, a novel immunomodulatory agent, does not cause nerve damage as one of its side effects. However, one of the limitations to using Revlimid is related to its renal (kidney) clearance. Approximately 20 percent of myeloma patients have some degree of abnormal kidney function. In patients with abnormal kidney function, Revlimid remains in the body longer and may cause bone marrow suppression. These patients have lower blood counts, which may be associated with infections (low white counts), anemia (low red counts) or bleeding risks (low platelet counts).
In a recent study, Revlimid was administered to people without myeloma who had varying degrees of kidney failure to determine an acceptable dosing schedule. These results have been incorporated into treatment guidelines allowing for the safe treatment of myeloma patients with Revlimid.
In summary, we have established safer treatment approaches with the two most active agents for the treatment of myeloma. These modifications of prior administration schedules for Velcade and Revlimid will allow us to maintain excellent responses and improve survival while decreasing the side effects associated with these treatments. This is a win-win situation – longer remissions, longer survival, and improved quality of life!
Dr. David H. Vesole is Co-Chief of the Myeloma Division and Director of Myeloma Research at The John Theurer Cancer Center at Hackensack University Medical Center. Dr. Vesole writes a quarterly column for The Myeloma Beacon.
I have been getting my biweekly Velcade subcutaneously for several months now. I experience a reddened rash over the site (abdomen) which appears on the second day, lasting about a week. It becomes quite itchy and slightly swollen. At this point , I'm note wanting to go back to IV to save damage to my veins, but I wonder if there is something that can minize the disconfort and avoid a further sensitizing reaction.
Thanks you Dr. Vesole. As you have pointed out the the importance of dosing is vitally important.(don't forget about "low dose" dex.)
However, we can't stop there. We must reduce the variability in response and side effects by "individualizing" the dosing to the patient. We have just completed a study showing that individualizing the starting dosing of the MPT combo for patients not candidates for transplant will have a dramatic difference on cumulative exposure which is a marker of side effects. We will send the abstract for your comments. If you want a few chuckles you might also look at my opinion piece in the Beacon on the same topic. Gary Blau
My husband was put on 1x weekly Velcade from the start, side effects minimal. But does anyone have an ETA on the sub-q from Millennium? When will it be widely available? My husband travels a lot and it would be so much nicer for us.
Have been on Revlimid for 20 months. Was on 10 mg for 30 days, now cut back to 21 days on, 7 off due to developing neuropathy. I have to say that it does cause nerve damage at least in some patients.
Thank you, Dr. Vesole, for your very informative article.
I just enjoyed my 85th weekly VRD MM maintenance treatment (out of a projected 156 weeks total) via UAMS's TT4 and am responding well. Treatment includes once weekly Velcade (2.0mg IV), Rev (15mg - 21 days on/7 days off) and 12mg Dex on Velcade infusion day.
I am a 52yo male, in CR since after my first ASCT in 3/09 with a dx of IgG kappa. Lots of bone problems, history of DVT/PE, no kidney issues (although I have a consistent high normal creatinine level), with the typical low RBC and Platelet counts.
Q? I have mild PN in my feet and hands and am wondering if there is evidence that a subQ Velcade approach could possibly lessen even my mild PN?
I have blood work done each week via an IV (no port & no vein problems evidenced) and am thinking that if I give the subQ Velcade a shot - sorry - and use normal venipuncture, I could skip the IV which is left in for a few hours of waiting for labs. Any advantage in this?
And do you have any idea whether there would be a cost difference using subQ vs IV? Couldn't hurt to ask...
Thank you! BTW - I very much enjoyed your presentation at the Kansas City area IMF patient seminar a while back and even found the humor in your teasing me about comparing my UAMS Total Therapy treatment to a nuclear bomb drop... I think you were teasing!
Thank you for your continued work on behalf MM patients! All my best.
Sean M.
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