In the second article of a 2-part series, Jack Khouri, MD, discusses with a group of physicians what supportive care options, such as anti-nausea medicine and dose modifications, are important when treating a patient with relapsed/refractory in the third-line setting and beyond.
CASE SUMMARY
A 70-year-old White woman was diagnosed with stage I multiple myeloma and fluorescence in situ hybridization showed deletion 17p (del17p) in her disease. The patient had a prior medical history of stage 3 chronic kidney disease and moderate renal impairment. She declined autologous stem cell transplant, and received lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd). She had a very good partial response (VGPR), so lenalidomide maintenance was continued. Two years later the patient relapsed after reporting mild fatigue but continued to work full-time.
Bone marrow plasma cells, light chains, and M protein were all rising, and her kidney function worsened to stage IV chronic kidney disease. The patient was then given daratumumab (Darzalex), pomalidomide (Pomalyst), and dexamethasone and had a VGPR. One year later she experienced a second relapse of her disease with renal function continuing to decline. The patient was started on selinexor (Xpovio), bortezomib, and dexamethasone (XVd) based on her progressive renal impairment, del17p status, and prior therapies. She achieved a VGPR.
DISCUSION QUESTIONS
JACK KHOURI, MD: If you tell the patients that the first cycle [of treatment] is going to be hard, and then they're going to be OK, I think they'll do fine. What I try to tell them is that we get complete blood counts [CBCs] and a comprehensive metabolic panel [CMP] in order to monitor them in the first cycle, and then we will get them in for weekly hydration if we can and if they need it. [You should] check their CBCs and CMPs once a week, give them hydration as needed, and then if they do fine [with this, they will tolerate treatment well].
I also tell them that nausea is common with [selinexor], and the nausea as related [to dizziness] or the stomach. So what I put them on is daily olanzapine [Zyprexa], which tackles the [dizziness], and ondansetron [Zuplenz], which is a 5-HT3 receptor antagonist and basically tackles the stomach-related nausea. Once you put them on a dual nausea prophylaxis, they do well [with it], and I've rarely had to admit people [to the hospital] for adverse events [AEs] from selinexor.
WILLIAM TSE, MD: [For the patient's hydration, I also frequently check] with that part of monitoring, but I don't usually do a triplet of anti-nausea medication. I might use the other salvage therapy [and monitor] around the clock.... I want to minimize those kinds of drugs, so less is more.
BAIDEHI MAITI, MD: I have had only 1 patient I’ve used [this treatment and supportive care on]. I don't see a lot of patients with myeloma in the region, but [in this case] they did well with [selinexor]. I have a couple of patients who I thought about, once they progress after daratumumab, to get selinexor, carfilzomib [Kyprolis], and dexamethasone, but thankfully we haven't gotten there.
ANEEL CHOWDHARY, MD: I have 87-year-old patient who we've continued [treatment with] daratumumab and after the second line; it's almost like she is on a third-line daratumumab with low-dose pomalidomide, but she is progressing and not doing well. So, she's the 1 person I was thinking of putting on...a low dose of carfilzomib with selinexor. I was wondering for these elderly patients who are in that third-line setting, what has your experience been? If you support them well, then can they do well on this regimen?
JACK KHOURI, MD: I do have [elderly] patients like that in my clinic who are on selinexor and carfilzomib.... For a patient like this, what I would [do is a low dose of] carfilzomib and I would start selinexor at 40 mg, [especially for your patient] since she's 87 years old.1 Then I would see how she does with the first cycle and...you can increase [the dose] if her myeloma response is not great. But if she responds well to 40 mg then I would keep her on that dose and the low dose of carfilzomib. It's better to start low and then escalate if the response is not great, but it's good to start low and see if they tolerate it. If they have a response [to 40 mg of selinexor] then keep on the same dose, you don't have to increment it.
Reference:
Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3
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