Counseling Patients on Treatment With Selinexor for Multiple Myeloma

Ariel F. Grajales-Cruz, MD

Assistant Member in the Myeloma Section

Malignant Hematology Department

Moffitt Cancer Center & Research Institute

Tampa, FL

DISCUSSION QUESTIONS:

• How do you counsel patients when discussing selinexor (Xpovio) as an option?​
• What about for patients who will receive selinexor? ​
• If you use selinexor, what steps and supportive care do you routinely perform to help with tolerability?​
  • What is your approach to dose reduction?​
  • What is your approach to nausea/vomiting prophylaxis and hydration?​

ARIEL F. GRAJALES-CRUZ, MD: What is your experience? How do you counsel your patients about selinexor? How do you prepare your patients for the potential adverse events (AEs)? And what kind of supportive care do you provide them with?

AHSAN SHAH, MD: [When] counseling for toxicity…we have to talk to them about neuropathy. That’s an important one. Standard nausea, vomiting, and diarrhea are also relatively common. Then I think it’s a good idea that these patients meet with an ophthalmologist, as well, because of the ocular toxicity associated with this medication.

GRAJALES-CRUZ: Do you typically plan for intravenous hydration from time to time if the patient starts to become more nauseated, has weight loss, and a tougher time with the caloric intake?

SHAH: Always. Hydration goes a long way so that goes without saying. Any time a patient is struggling, we bring them in for hydration.

GRAJALES-CRUZ: How often would you do blood work for these patients? Because we know that selinexor can have hematological toxicities, are you doing once-a-week laboratory [testing]?

SHAH: Yes, I do it weekly. If the numbers and counts are dropping, then sometimes twice a week but typically weekly.

GRAJALES-CRUZ: Perfect. Is anybody else doing something different like nutritional consults or dose reductions?

DEBORAH GLICK, MD: I have not used selinexor, but like the other physicians, I would try to be vigilant about the nausea and vomiting and probably give antiemetics up-front as routine.

GRAJALES-CRUZ: Perfect. It’s always important to not only be on top of those but also to remember that dose reductions exist for a reason. If the patient is struggling with [blood] counts or pure gastrointestinal toxicity, then dose reductions can take you a long way and it can potentially allow the patient to stay on drug for a longer time.

[In addition to] blood work, complete blood counts, and comprehensive metabolic panel, remember that hyponatremia can happen with selinexor. The weight of these patients is very important because that will tell you how the patient is behaving. We know that our patients tend to underestimate the AEs to stay on the drug, but if the weight’s going down, then clearly the oral intake is also going down, so that’s very important to keep an eye on. Whenever we need to adjust dose, we should go for it because the most important part is to keep the patient on the drug rather than just take them off. As Dr Shah mentioned, hydration takes the patient a long way, and prophylactic antiemetics [are important]. We know that serotonin receptor antagonists are very important along with other medications like olanzapine [Zyprexa], for example. They’re very efficacious for the nausea prophylactic, and we should always consider them.

STORM [NCT02336815] was the original clinical trial [led to] approval back in 2019.¹ The schedule was pretty intense. It was 160 mg twice a week, so 80 mg biweekly.² That was pretty rough on these patients. The thrombocytopenia, neutropenia, nausea, fatigue, and hyponatremia were more meaningful than what we found on the BOSTON trial [NCT03110562], which was dosed at only 100 mg once weekly.³

We know that there is a dose-related meaning to these AEs, but also the most important part is that we should always keep in mind the treatment-related nausea was mild and transient whenever it was managed appropriately. More than 90% of the patients’ [nausea was] resolved within the first month. The most important part is just to push the patient through that first month and see how we can mitigate the AEs initially, and then they start cruising.

The BOSTON trial did require the serotonin antagonist to address the nausea and also allowed for other interventions as needed because, again, we want to make sure that the patient can tolerate it in the best possible way. Although the starting dose was 100 mg weekly, the most common dose was the first reduction, 80 mg once weekly.³ To be honest, that’s a dose that is pretty well tolerated but if you need to go down to 60 mg, feel free. I have plenty of patients on 60 mg who are doing well, and they tolerate the treatment in a better way. It [should not] become worse than the disease. If I am causing more symptoms than the myeloma, then clearly I’m doing something wrong and that’s my rule of thumb.

We know that the patients who did not get dose reductions on time had a shorter duration of response and shorter progression-free survival.⁴ So those early interventions will allow you to stick to the treatment, and, as a result, they will have almost a doubling in the PFS and that is very important. Not only are we doing what’s right for the patient but we’re making them feel better with those dose reductions, and we always should strive for that. The AEs reported with dose reductions were lower, so we always have to make sure that we do what’s right for the patient altogether.

DISCUSSION QUESTION

• Will this discussion and data review impact your future practice?

GRAJALES-CRUZ: How does the talk that we just have impact your thought process about selinexor altogether? Do you think that this is enough for you to consider it?

RAJI SHAMEEM, MD: I think [I feel] positive. I used it when it was first approved in a penta-refractory patient, and the gastrointestinal toxicity was challenging but with lower dose and the data, I think it is a good option. If I control the nausea, I think they could have meaningful benefit from it. I did change my mind by looking at the data.

JAY WANG, MD:I started somebody on carfilzomib [Kyprolis]-based treatment she didn’t tolerate it too well. In fact, she was admitted recently and I said, “We’re going to try selinexor next.” I’m going to try it for the next appropriate patients. I’ve not used it for a time but the data look promising with the lower dose.

GRAJALES-CRUZ: That’s exactly what I want you to take from this. These are drugs that we’re not always very familiar with, especially because multiple myeloma remains a very rare disease altogether. It’s just a fraction of what your real practice looks like on a daily basis.

_References:

_{1. FDA grants accelerated approval to selinexor for multiple myeloma. News release. FDA. July 3, 2019. Accessed July 26, 2023. https://tinyurl.com/5n8r2exw}

_{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. 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}

_{4. Jagannath S, Facon T, Badros AZ, et al. Clinical outcomes in patients (pts) with dose reduction of selinexor in combination with bortezomib, and dexamethasone (XVd) in previously treated multiple myeloma from the BOSTON study. Blood. 2021;138(suppl 1):3793. doi:10.1182/blood-2021-146003}