Lower-Dose Selinexor Data Lead to Patient Selection Questions in RRMM

Jonathan L. Kaufman, MD

David Bankes Glass Multiple Myeloma Professorship

Professor, Department of Hematology and Medical Oncology

Emory University School of Medicine

Medical Director and Section Chief, Ambulatory Infusion Centers

Winship Cancer Institute of Emory University

Atlanta, GA

[Continued from Part 1]

CASE SUMMARY

• A 76-year-old man was diagnosed 5 years ago with multiple myeloma (IgG-kappa)​
• Hypertension well controlled with lisinopril​
• He noticed a progressive decline in his stamina, and now presents to his physician with bone pain and fatigue​.
• Serum free light chain lambda at diagnosis was 8842 mg/L​
• Standard risk by fluorescence in situ hybridization​
• ECOG performance status of 1; IMWG (International Myeloma Working Group) Frailty Status: Intermediate-Frail​
• Based on age and risk status, transplant is not preferred for this patient​.
• He received daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (DRd) with a complete response​.

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Three years later​

• He reported increasing fatigue and bone pain during his annual check-up with his oncologist​.
• PET scan – uptake in multiple bony lesions on ribs and femur​
• The patient wished to continue therapy and was interested to hear what options remain​.

DISCUSSION QUESTIONS

• How do you counsel patients with relapsed/refractory multiple myeloma (RRMM) regarding selinexor (Xpovio) as a treatment option?​
• If you use selinexor, what steps and supportive care do you proactively perform to improve tolerability?​
• What is your approach to dose reduction?

JONATHAN L. KAUFMAN, MD: If you’re going to give selinexor in RRMM, you want to monitor them carefully. [You should monitor standard complete blood] counts, chemistries, nutritional status, and volume status.¹ You need to make sure you’re up to date with their hydration; oftentimes, they’ll need dual antiemetic. The dual antiemetic therapy is much less important when you’re using 40 mg or 60 mg. The last time I spoke with [the company] who makes selinexor, I said they should rename 40 mg of selinexor to something different, because it’s almost like a different drug. We know about dose reductions. I start at 40 mg to 60 mg. I think 60 mg is OK to start, knowing you could dose reduce to 40 mg.

[The impact of dosing] was an important outcome in BOSTON [NCT03110562]. If the patient had toxicity and you dose reduced, they did better than those patients who didn’t receive a dose reduction [HR for progression or death, 0.5678; 95% CI, 0.3614-0.8919; P = .0065].² Maybe [the other patients] didn’t dose reduce, and maybe they came off [instead], but dose reductions are OK, and patients do better for dose reductions because they’re able to stay on longer.

Dr Hanna was the one who asked, “Why aren’t we considering this?” The question is, we talk about a lot about KPd [carfilzomib (Kyprolis), pomalidomide (Pomalyst), and dexamethasone], and PVd [pomalidomide, bortezomib (Velcade), and dexamethasone]. Is anybody looking at these data and saying, “Maybe I need to add this to my thoughts,” because we got a good rundown of why we should do it from Dr Hanna.

CHARLES KUZMA, MD: [Dr Kaufman], you see tons of patients with RRMM at an academic institution. How many times have you used selinexor over the past year and then how many of them were not in the third or fourth line of therapy, where you were trying to get someone the fifth line of therapy to offer them cellular therapy?

KAUFMAN: I use it in the third and fourth line. I’ve been very impressed in the post-daratumumab [Darzalex] space. I like to use it in the pre-CAR [chimeric antigen receptor] T-cell therapy, pre-bispecific space. That’s where I use it. I don’t use the BOSTON regimen, but it’s there. The question is, “Who is it there for?” The data look good for those patients who haven’t had a proteasome inhibitor and who you think you can tolerate it. That’s where your options are. But historically, I’ve used it in the third and fourth lines.

SHEBLI ATRASH, MD: The way I think about it, if we start quadruplets in the frontline, and the patient progressed after that, we have already [exhausted] 3 drugs. Then in second line, with KPd, we would [exhaust] the other 2 drugs that we have. We run out of options immediately within 2 lines nowadays, or sometimes within 3 lines, so you need options to keep going. I agree, I’m not using it much of the early-line [selinexor] therapy, even though the results from the trial are convincing, but they need more data with a new dose.

KAUFMAN: The most common regimen I use is XPd [selinexor, pomalidomide, dexamethasone]. [The phase 1b/2 STOMP trial (NCT02343042)] used 60 mg or 80 mg, but I use 40 mg.³ In that situation, I commonly will use it with carfilzomib. [In the trial], they used 80 mg or 100 mg, but I’ll use 60 mg to 80 mg with carfilzomib, more likely 60 mg.⁴ We sometimes have very aggressive maintenance approaches where we use 3-drug maintenance; if someone’s progressing on 3-drug maintenance, and that doesn’t include daratumumab, [then I use] daratumumab plus selinexor. This is the most common way that I’ve been using it.

REFERENCES:

1. Xpovio. Prescribing information. Karyopharm Therapeutics, Inc; 2022. Accessed April 18, 2024. https://tinyurl.com/2ps46vk7

2. Jagannath S, Facon T, Badros A, 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

3. White DJ, Chen CI, Baljevic M, et al. Once weekly oral selinexor, pomalidomide, and dexamethasone in relapsed refractory multiple myeloma. Blood. 2021;138(suppl_1):2748. doi:10.1182/blood-2021-148759

4. Efficacy and safety of selinexor-containing regimens in patients with multiple myeloma previously treated with Anti-CD38 monoclonal antibodies (αCD38 mAb). Blood. 2021;138(suppl_1):1651. doi:10.1182/blood-2021-150232