Managing Adverse Events With Selinexor in R/R Multiple Myeloma

Sumit Madan, MD

Hematologist-Oncologist

Banner MD Anderson Cancer Center

Phoenix, AZ

DISCUSSION QUESTIONS

• What are the challenges to using selinexor (Xpovio) for patients with relapsed/refractory multiple myeloma?
• What are your approaches to managing the toxicities of selinexor-based combinations?

ASHKAN LASHKARI, MD: One of the challenges with this drug is the adverse events [AEs] and the dosing goes into that. I have generally given it to patients both in combination and as a single agent for multiple myeloma as a once weekly drug.¹ The problem is that a lot of physicians don’t have familiarity with it, and you have to create that familiarity yourself. We don’t have a lot of guidelines that dictate what dosing is best tolerated. Using olanzapine [Zyprexa] for the nausea associated with this drug can be very helpful, and I talk to my patients about that up front. The use of appetite-stimulating agents is important because of the anorexia that can develop when they’re on this drug. The challenges revolve around with the dose and managing the AEs, and that’s a little challenging especially when you’re dealing with patients who may be already compromised as a result of their disease.

MOHAMMAD ZIARI, MD: I agree with Dr Lashkari, and [it is important] to strategize the treatment for nausea or vomiting through discussion with the patient. Because the majority of these patients experience the nausea or vomiting the first couple of months, and if they tolerate it, it is diminished significantly. Olanzapine is also a drug of choice I use for patients with selinexor because it is great [at passing] the [blood-]brain barrier, the same thing selinexor does. If you use olanzapine, you can do it in combination with a dose of 2.5 mg or 5 mg. It is a very cheap drug and can control nausea and vomiting very well.

Besides that, in the STORM trial [NCT02336815], the majority of the patients eventually ended up using 80 mg [twice weekly] and none ever saw 100 mg once a week.² It was too much in combination with bortezomib [Velcade] with dexamethasone. In the STOMP trial [NCT02343042], they had different dosages [in other arms whose results] are not out yet, but for pomalidomide [Pomalyst] it was 60 mg and for carfilzomib [Kyprolis], [80 mg or 100 mg].³ But I think 100 mg was too much. The gastrointestinal AEs were important, and the neutropenia also needs to be addressed. We [should] make sure that we tell the patient so they understand the situation of nausea and vomiting with the different [combination] then we can control it.

SUMIT MADAN, MD: This is a good discussion around the AEs of selinexor. One of the things that I always do is to counsel the patients quite a bit to make them understand what they are dealing with, especially when we start out. I’m pretty aggressive with the prophylaxis that I provide to my patients in terms of nausea and vomiting. I completely agree with using at least 2 drugs, ondansetron [Zofran] as well as olanzapine. We tell them exactly how to take it around the clock. Don’t wait for them to have nausea first. That’s extremely important. The other drug is aprepitant [Emend] that can also be used for the nausea and vomiting. Of course, steroids always work really well.

The other is monitoring these patients carefully once a week to check on their nutritional status and see how well they’re eating, and to check their serum sodium. Sometimes these patients may need salt tabs and intravenous fluids as well.

The third is the fatigue, which I have noticed in my patients as well. I’m dealing with less nausea and vomiting now with the once weekly dose, and after we decrease the dose from 100 mg to 80 mg, sometimes even to 60 mg. I have a couple of patients on 40 mg doing well.

But some of these patients experience fatigue and sometimes fitting the dose of the dexamethasone helps, to give the dexamethasone on the day when they’re feeling the fatigue the most. Otherwise, you can use drugs like methylphenidate as well. In my experience, I’ve seen a little more fatigue compared with the nausea, vomiting, as well as the hyponatremia scenarios.

DONG XIANG, MD: I have not used selinexor before, and luckily there are other combinations that works well for my patients. But it’s a very educational session to learn from others about AEs. It may be in the future I can use that for some patients who progressed on other lines of therapy.

NIHAL ABDULLA, MD: I prescribed it a few weeks ago and we are still waiting on the approval. I was using selinexor with bortezomib. But on hearing all that, I will be checking my chart to see what dose I indicated for this patient. I might have to make some adjustments for the nausea. But I have not had any experience yet.

_References:

_{1. Xpovio. Prescribing information. Karyopharm Therapeutics Inc; 2020. Accessed March 20, 2023. https://bit.ly/3FArFSR}

_{2. Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727-738. doi:10.1056/NEJMoa1903455}

_{3. Bahlis NJ, Sutherland H, White D, et al. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018;132(24):2546-2554. doi:10.1182/blood-2018-06-858852}