Role of Toxicity Management in RRMM
An expert hematologist-oncologist provides his perspective on the importance of managing toxicities in patients with relapsed/refractory multiple myeloma.
Clifton C. Mo, MD: In order to prevent and minimize toxicities associated with selinexor, we are starting patients on fairly robust antiemetic prophylaxis. This would include 2 antiemetic prophylactic medications: usually a 5-HT3 blocker plus either low-dose Zyprexa [olanzapine] or a neurokinin-1 inhibitor like Cinvanti [aprepitant]. We then obviously give the patient antiemetic medication for PRN [as needed] use at home.
Arguably, this may not be necessary for some or even most patients who get only once-weekly selinexor, but because of the potential for the GI [gastrointestinal] toxicity, we still start fairly aggressively in terms of prophylaxis. But we have a low threshold to de-escalate the prophylaxis in patients who are having no problems with GI toxicity, obviously. At least for the first cycle or two, weekly blood work to include chemistry checks are important because we see some incidence of hyponatremia in patients who are treated with selinexor. This is usually low grade, asymptomatic, and effectively managed with appropriate hydration as well as salt tablets as necessary. We check the blood work fairly frequently but not necessarily forever in patients who don’t demonstrate any evidence of electrolyte imbalance. We do this for at least the first cycle or two.
Importantly, selinexor is not associated with an increased risk of opportunistic infections like we see in some other myeloma agents. I don’t think patients necessarily need to be given prophylaxis for that specific indication. We also don’t see an increased risk of thrombosis. If the selinexor is being partnered with a proteasome inhibitor or an anti-CD38 monoclonal antibody as opposed to an IMiD [immunomodulatory drug], then the patient doesn’t necessarily need to receive thrombotic prophylaxis. That draws on another important point: even though, for some patients, selinexor can be difficult to tolerate, especially in the twice-weekly dosing schedule, the high-grade toxicities that we are seeing from selinexor are things like fatigue and nausea, which are not vital organ toxicities, such as cardiotoxicity, pulmonary events, or renal events that we can see with other agents. They are almost always rapidly reversible with suspension of the drug.
Interestingly, unlike most of our agents, selinexor has excellent penetration into the central nervous system [CNS], so a lot of the toxicities that we’re seeing in terms of the fatigue, asthenia, and nausea are probably related to the effect of CNS penetration. I won’t go too much into the potential benefits of that, but in patients who have extramedullary disease or perhaps CNS myeloma, there may be an increasing role for a drug like selinexor in the future.
My experience with selinexor-containing regimens in patients with relapsed/refractory multiple myeloma has been positive overall. I will say that I don’t prescribe or recommend the twice-weekly dosing of selinexor, which is how it was initially FDA approved. I don’t like saying “never,” but I virtually never recommend the twice-weekly dosing schedule because the once-weekly data from both the BOSTON and STOMP trials are so encouraging in terms of efficacy as well as safety and tolerability that I almost always prescribe or recommend selinexor as a once-weekly drug in combination with another novel myeloma agent.
In this context, I’ve had pretty good luck, personally. I still have patients who have some difficulty with adverse effects from selinexor, although I find that it’s generally easily managed with the supportive and prophylactic care I just mentioned. There are probably still patients who won’t be able to stay on selinexor due to some of these nonhematologic adverse effects. But the data are showing that this is going to be the exception much more than the rule and that this is going to be a good and generally well-tolerated options for patients of all cytogenetic risk as well as those in all age categories, potentially.
The other thing I’ll say about selinexor is that I find it to be a drug that tends to work pretty darn rapidly when it does work. The average time to response is on the order of weeks as opposed to months, which is important in general, but especially important in patients who have seen multiple lines of therapy, or who have fairly rapid disease progression or clinical relapse. We have a good chance of re-establishing disease control and providing the patients meaningful and symptomatic benefit in a short amount of time with a pill-based regimen as opposed to cytotoxic chemotherapy or something along those lines. In that sense, I find selinexor to be helpful not only in terms of likelihood of response, or likelihood of durable response, but also in terms of likelihood of immediate response, which is important.
Transcript edited for clarity.
Case: A 79-Year-Old Woman with Multiple Myeloma
Initial Presentation
- A 79-year-old woman presented with intermittent nausea, decreased appetite and tingling and numbness in her feet bilaterally
- PMH: HTN, medically controlled
- PE: thin, tired appearing woman, otherwise unremarkable; grade I peripheral neuropathy
- ECOG PS 0
Clinical Workup
- Labs: Hb 9.6 g/dL, calcium 10.5 mg/dL, LDH 210 U/L, creatinine 1.1 mg/dL, albumin 3.8 g/dL, beta-2 microglobulin 3.2 mcg/mL, M-protein 2.9 g/dL, serum free kappa light chains 4.4 mg/dL, CLCr 35mL/min
- Hepatitis B and C negative
- Skeletal survey and MRI showed a lytic lesion in her spine L3/L4
- Bone marrow shows 45% clonal plasma cells IgG k
- FISH: hyperdiploid
- Diagnosis: R-ISS stage I MM
Treatment
- Initiated lenalidomide + bortezomib + dexamethasone for 8 cycles + lenalidomide maintenance for 9 months
- Follow-up at that time revealed disease progression
- Initiated selinexor + bortezomib + dexamethasone
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