Treating Patients With Multiple Myeloma in the VA
Moderator
João Ascensão, MD, PhD, is a professor in the Department of Medicine and Immunology at George Washington University School of Medicine and chief hematologist and chairman of the R&D Committee at the Washington DC VA Medical Center, both in Washington, DC. He is also a clinical professor of medicine at Uniformed Services University in Bethesda, Maryland. In 2015 Dr. Ascensão served as president of the Association of VA Hematology/Oncology (AVAHO).
Panelists
Thomas R. Chauncey, MD, PhD, is an associate professor of medicine and oncology at the University of Washington, and an associate member of the Fred Hutchinson Cancer Research Center. Dr. Chauncey is director of the Marrow Transplant Unit at the VA Puget Sound Health Care System, all in Seattle.
Sean Cosgriff, PharmD, BCOP, is the hematology/oncology clinical specialist at the VA Portland Health Care System and affiliate faculty at Oregon State and Pacific University, both in Portland, Oregon. In 2014 Dr. Cosgriff served as AVAHO president.
Paulette Mehta, MD, MPH, is a professor of hematology/oncology at the University of Arkansas and a physician at the Central Arkansas Veterans Healthcare System, both in Little Rock. In 2010, Dr. Mehta served as AVAHO president.
G. David Roodman, MD, PhD, is the Kenneth Wiseman professor of medicine and director of the hematology/oncology department at Indiana University School of Medicine. Dr. Roodman is also a staff physician at the Roudebush VA Hospital Healthcare System in Indianapolis.
Nikhil C. Munshi, MD, is a professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, both in Boston, Massachusetts. Dr. Munshi is also a staff physician at the VA Boston Healthcare System at the Jamaica Plain Campus.
An alternative people use that has a financial difference is to use a proteasome inhibitor with cyclophosphamide and dexamethasone, a VCD-like regimen. The study is going to use ixazomib, cyclophosphamide, and dexamethasone followed by ixazomib maintenance. That’s the usual induction regimen.
The question is do we do this differently whether the patient is high risk or low risk? My personal bias in the answer is, not really. At the beginning, we will present the best treatment for the patient’s health. If they are older patients with a lot of comorbidities, which is more important, we can use weekly bortezomib instead of using the full dose. We can use subcutaneous weekly bortezomib or a similar 3-drug regimen. And so high risk or low risk doesn’t change how we’re doing the beginning.
The place where the risk stratification comes into the picture is if patients get a transplant. We are beginning to do posttransplant consolidation, and that’s where we would add 2 cycles of consolidation. If consolidation is not done, for high-risk patients one may do maintenance with 2 drugs like bortezomib and lenalidomide alone; whereas in a low-risk patient, you could do lenalidomide only and not use bortezomib with it. This is the impact of risk stratification as far as what we do. It comes more at the later time rather than earlier time point.
Dr. Mehta. There are still a lot of unanswered questions. One area where I think the VA is very good at becoming involved, if we choose to do so, would be some of the drug dosings. For example, dexamethasone used to be used in high dose and the ECOG study showed that you can use it in lower dose weekly rather than 4 days on, 4 days off. The Myeloma In VA (MIVA) group led by Dr. Munshi did a study looking at different doses of lenalidomide. There’s still unanswered questions even in this standard of care regimen that we use where we could try to make the regimen more tolerable for patients.
Dr. Roodman. RVd (modified RVD) has been piloted by Dr. Noopur Raje at Mass General, but I don’t think it’s a large study. She uses it in older patients. To follow-up on what you said, which I think is a really great idea, we could look at RVd as well as 2 doses of dexamethasone, or use oral proteasome antagonists instead.
Dr. Mehta. Yes, to reduce the neurotoxicity.
Dr. Roodman. That is correct. But I think the VA is set up to look at those kinds of questions because most of our patients are older.
Dr. Mehta. They have all the comorbidities.
Dr. Chauncey. We have what we think is an optimal regimen for an optimal patient, and then we have what we often see in the clinic. I’m not sure of the quantitative VA demographics, but if you look at the U.S. myeloma population, the median age is 70 years. While a triplet like
RVd or a carfilzomib-based triplet is probably optimal based on depth of response and the theoretical aspect of suppression of all subclones, it’s not really an accessible regimen for many patients that I see in clinic who are not transplant eligible.
For the nontransplant patients and more frail patients, the doublets or the cyclophosphamide/bortezomib/dexamethasone are reasonable options. I know there are proponents saying that everybody should get RVd or dose-attenuated RVd; I don’t think that’s practical for many of the patients that we see in our clinics.
Dr. Mehta. Why is it not practical in most of your patients? Because they have to come once a week to the clinic?
Dr. Chauncey. That’s part of it, but I find that it’s often too intense with excessive toxicity. The patients are older with comorbidities and they have more limited physiologic reserve. Part of it is coming to clinic, and that’s where all oral regimens such as Rd are useful. I don’t know that if you have an older patient and you see a good response that you’re tracking in terms of their Mspike (monoclonal protein) and their CRAB criteria, that everybody requires the aggressive approach of RVd or a similar triplet with a proteasome inhibitor, an IMiD [immunomodulator drug], and a steroid as induction therapy.
This is true even for some of the older patients who come to autologous transplantation. The data we talk about are in a younger group of patients who can tolerate the full dose of those regimens. The all-oral regimens are attractive, but it’s also quite a financial burden, maybe not to an individual patient, but certainly to the whole health care system. I’m not sure if there is a depth or durability of response advantage for the oral proteasome inhibitor over those available as IV or subcutaneous dosing.
Pricing
Dr. Ascensão. It’s interesting you bring that up because at the Washington DC VAMC, ixazomib may be priced similarly to bortezomib.
Dr. Chauncey. Well that would be very good and very interesting. It’s possible the federal pricing would make it a lot more attractive. It’s not the case outside of the VA, but there the cost burden for oral medication is often shifted to the patient.
Dr. Cosgriff. The price of carfilzomib is about $7,000 to $9,000 per month or per cycle. When we priced ixazomib here in Portland, it actually was more expensive than bortezomib, but it was cheaper than carfilzomib.
Dr. Mehta. If we can do a drug company-sponsored study, the ixazomib people would surely be interested in its usefulness as a triplet in VA patients. It also would be good for the VA patient because you don’t have to come once a week and it has much less neurotoxicity compared to the other proteasome inhibitors, which is a big problem.
Dr. Chauncey. That would be a great study to offer the right patient. I see a lot of myeloma patients in clinic that aren’t really eligible for transplantation. Many of those patients do well on doublet therapy, though they will often require dose adjustments, both down and up, as well as tracking disease status.
Dr. Cosgriff. In Portland, we’re using a lenalidomidebased regimen as a first-line therapy. We’re starting to see more and more individuals starting RVD upfront. There are some select individuals who have diabetic neuropathy or something like that, who may go on just
a lenalidomide plus dexamethasone, leaving out the bortezomib because of neuropathy issues.
Our second-line choice at this point in time has been carfilzomib, but with ixazomib being a cheaper option, we may actually consider switching over to that as a second-line choice. When you look at the clinical trials they cite in the product literature, the grade 1 neuropathy is about 18% with ixazomib and 14% with the placebo arm, so it does add some peripheral neuropathy. Maybe not as much as we would think.
While these oral agents and all-oral regimens are nice to have, we still bring in the patients for clinic and for monitoring of white blood count. It doesn’t necessarily decrease the burden of clinic visits. We still have to get lab draws. Yes, the patient is not sitting in a chair waiting for the bortezomib infusion to be mixed by the pharmacy, but we still have considerations for travel and those types of things.
We treat the entire state of Oregon and parts of southwest Washington. Fortunately, we have community-based outpatient clinics (CBOCs) and VAMCs in other areas of the state, and we also utilize places like Walla Walla and Spokane, Washington, where we can draw and check labs remotely, which decreases the travel burden, but it still is a burden to the patient to actually go in for lab tests. We’re not looking at ixazomib as a first line currently.
We’re going to wait for data to be published on ixazomib in the first line. In a couple of presentations, researchers have suggested that if you tease the data, ixazomib may be inferior to bortezomib in the first-line setting. It will be interesting to see what the data say for that as far as a first-line setting choice.
Dr. Chauncey. I second what Dr. Cosgriff said. You can’t just give patients 3 bottles of pills and say, “See you in 3 months.” Here in the Northwest we cover large rural areas, and there are many CBOCs whose labs feed directly into our CPRS (Computerized Patient Record System) so it’s very accessible and easy to follow patients that come in less frequently, but that doesn’t change the need for regular clinical follow-up. The other thing I’d say is the noncomparative data of carfilzomib/lenalidomide/dexamethasone (CRD) is quite compelling in terms of depth and duration of response. We usually don’t want to accept convenience over efficacy. Whether that durability translates long term, we don’t really know, but I think right now, CRD is the best available regimen, again, with the caveat that it’s not really accessible to patients of all ages and performance status.
