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.
