Pat Killingsworth said, “ Dr. Orlowski is an exceptional myeloma expert. I would rank him among the top five in the world.”
Nick Van Dyke said, “That was a great call and Dr. Orlowski was fantastic, both in terms of knowledge and in terms of “bedside manner” if you will. What a great guy!”
Jack Aiello said, ““I’ve seen & heard Dr. Orlowski speak many times and am always impressed by his ability to clearly articulate answers to complex myeloma questions so that patients/caregivers can understand and learn more about our disease.”
I also was very impressed with Dr. Orlowski’s depth of understanding of Multiple Myeloma and how skillfully he was able to put it into terms that the panel, patients, and caregivers can understand. You can listen to a rebroadcast of the entire program is you just CLICK HERE!
If you would like a summary of the presentation and discussion, I have provided a summary of the broadcast in the following paragraphs. If you would like to follow Dr. Orlowski on Twitter his address is: https://twitter.com/Myeloma_Doc
Combinations for Newly Diagnosed
Dr. Orlowski started his discussion of “Exciting New Drugs and Combinations for Myeloma” by stating that he was recently at the early April International Myeloma Workshop in Kyoto, Japan and so he had some of the most recent updates on treatments. He felt the focus was on the use of combination regimens and believed that these combinations were the best way to get to a myeloma cure.
In the low risk patients there were excellent results from two drug combinations such as Vd(Velcade, dex) or Rd(Revlimid, dex) and three drug combinations of VRd(Velcade, Revlimid, dex), and CVd(Cytoxin, Velcade, dex). All of these work well, but none of these combinations will provide 100% complete response.
Exciting New Combinations for the Newly Diagnosed
KRd or Krypolis, Revlimid, and dexamethasone is a new combination in phase one and two trials in the newly diagnosed setting that has a remarkable almost 100% response rate. It appears to have a higher CR(complete response) rate or improved quality of response. The study is being coordinated by the US Cooperative Network and would be a great clinical trial for anyone who is newly diagnosed.
High Risk Newly Diagnosed Patients Remain a Challenge
For those patients who are considered high risk by either evidence of the 17p deletion based on the FISH test, or have a high risk signature from the 70 gene array panel, the outlook needs to improve. These patients, who represent 15 to 20% of all patients, have a life expectancy of only 3 years, with the current standard of care VRd(Vecade, Revlimid, dex) Induction, and followed by VRd maintenance.
An exciting new 4 drug combination includes a new antibody drug Elotuzumab, along with Velcade,Revlimid, and dex, or EVRd. Elotuzumab is an antibody that attaches to the myeloma cell and tells the immune system where the myeloma is, so the immune system can then target the cancer cells. This may have fewer side effects because it is a targeted therapy. The question to answer is whether this 4 drug combination is better than the current VRd standard of care.
Other New or Recently Approved Drugs
Ixazomib is in the same class of drugs as Velcade, however it is an oral proteasome inhibitor, and does not require a hospital visit for infusion. A trial using Ixazomib with Revlimid and dex or IRd has shown good results as presented in Kyoto, Japan. This combination provides a much better quality of life because the patient can take this oral therapy at home.
The recent approval of Kyrolis in July of 2012 and Polmalidamide in Feburary of 2013 for use in the Relapse and Refractory(RR) setting has shown a huge benefit to these RR patients. The most benefit from these drugs appears to be in combination with other drugs. An MD Anderson led study using KPd(Kyprolis, Polmalidamide, and dex) in the RR setting has shown a response rate of 77% in heavily pretreated patients. What is great about this combination is that it can be used outside the clinical trial setting by your local hematologist oncologist.
Another combination that is being evaluated by MD Anderson is the combination of Thalidomid, Relimid, and dex or TRd. These drugs (TR) are in the same class of drugs, but in combination have shown a response on patients who have progressed on Revlimid. This is also an all oral regimen and has had a 50 to 60% response rate.
Daratumumab is another new antibody drug under development. It binds to a different protein on the myeloma cell and helps the immune system find a good target. It has had a nice response rate with heavily pretreated myeloma patients. There will be a large trial coming up which should result in FDA approval.
ARRY 520 is a drug which targets a protein that inhibits myeloma cells from duplicating, and has no potential for neuropathy at all. ARRY 520(no name chosen as yet), plus Krypolis, and dex or AKd has shown good activity even for patients who have progressed on Velcade, Revlimid, and dex. This combination will be in test across the country.
Dr. Orlowski, mentioned that he believes that there are two major spheres of thought, one of which is to use 1 or 2 drugs and save others available for relapse, or use combination of drugs early in the disease as possible(both newly diagnosed and RR) The data in ongoing, however there is a growing number of multiple myeloma specialists that believe the use of the combinations works better. Three and four drug combinations are better that two drug combinations. Although transplant was not mentioned in the doctor’s presentation, he indicated later in the Q&A section that his standard of care would be induction(2 to 4 drug), transplant, and then maintenance.
After the doctor’s presentation, he took several questions from the audience. There were 22 questions entered, which Nick and Jack were kind enough to consolidate into 11, plus we had a few additional questions from the panel members. Please listen to this discussion if you would like to hear all of what was said, however I will summarize what I felt were some of the most interesting findings.
Dr. Orlowski felt that tandem transplants may be effective for some patients, but only those that did not get a CR(Complete Response) or the NCR(Near Complete Response). In most other cases he felt that in the era of the newer novel agents the induction therapies are now far superior to those used in the pre novel agent era. He noted there will be a large US trial which will compare induction with VRd(Velcade, Revlimid, and dex) with early transplant, and others that delay transplant to relapse. Dr. Orlowski feels that the myeloma cells are more sensitive to all drugs at the time of diagnosis when they have not developed any drug resistance. He would consider induction(2 to 4 drugs), transplant, and maintenance as his standard of care.
Pat had asked if there has been any trials that put the two antibodies(elotuzumab and daratumumab) in combination. Dr. Orlowski thought that would be an excellent idea if used in conjunction with Revlimid.
MD Anderson, has a myeloma immunotherapy project under a grant from the National Cancer Institute called SPORE. It has 4 different components as outlined in the abstract found if you CLICK HERE. The myeloma M protein is isolated prior to treatment and then used as a vaccine which trains the immune system to destroy the myeloma cancer cells. They plan to use this in conjunction with transplant, and if it works after transplant it may be tried prior to transplant. Another element of this project is designed to train the patients T cells to attack the patient’s myeloma cells.
Concern over being on the placebo side of a clinical trial, and getting substandard care was expressed. In the context of clinical trials, placebos are usually not used in phase 1 and 2 studies, but only used in phase 3 trials which usually will compare the current best practice standard of care with a placebo, versus the standard of care plus a new drug. In addition, any patient can opt out of a trial if the patient chooses another course of care.
The Black Swan initiative is a hot topic and MRD(minimum residual disease) as a measure of response is integral to the program. Dr. Orlowski provided a history of myeloma disease measurement, and concluded that FISH, 70 gene array, and the 3 different ways of determining MRD are all great tools for use to detect low levels of disease and help determine if more treatment is needed or not. He believes that 10 to 20% of patients stay in CR for 10 years or greater and they may be cured.
Please listen to the entire broadcast to hear additional Q & A on 1) tests used to determine risk, and ways to use this data to determine treatment 2) the use of Ixazomib, Revlimib, and dex as an all oral maintenance regimen 3) treatment for high risk smoldering myeloma or treating myeloma now in a MGUS state 4) Is IgD myeloma more aggressive 5) GI issues from melphalan and long term maintenance therapy and, 6) body rash from Revlimid use.
I hope you find value from this exceptional program, and as always may God Bless your Myeloma journey. Gary Petersenfirstname.lastname@example.org
For more information on mulitple myeloma go to www.myelomasurvival.com or you can follow me on twitter at: https://twitter.com/grpetersen1