Physicians Discuss Options for Second Relapse in Multiple Myeloma

Ariel F. Grajales-Cruz, MD

Assistant Member in the Myeloma Section

Malignant Hematology Department

Moffitt Cancer Center & Research Institute

Tampa, FL

CASE SUMMARY

A 70-year-old White woman was diagnosed with stage I multiple myeloma. She had a medical history including stage 3 chronic kidney disease and mild renal impairment. Fluorescence in situ hybridization showed a 17p deletion (del[17p]) alteration. The patient declined autologous stem cell transplant.

She received lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone​ and had a best response of very good partial response (VGPR). She continued lenalidomide maintenance. Two years later, on routine follow-up, the patient reported mild fatigue​.Bone marrow plasma cells, light chains, and M protein were rising,​ and kidney function was worsening (now stage IV chronic kidney disease)​. ​The patient received daratumumab (Darzalex), pomalidomide (Pomalyst), and dexamethasone and had a best response of very good partial response. One year later, a second relapse was discovered​; kidney function continues to decline​.

DISCUSSION QUESTIONS:

• What regimen are you most likely to recommend for this patient now?
• What are the goals of therapy for a patient like this? ​
• What patient-, disease-, and therapy-related factors influence your recommendation for next-line therapy for a 73-year-old patient with worsening kidney function at second relapse?​

ARIEL F. GRAJALES-CRUZ, MD: What would any of you do for this patient? [There’s] a carfilzomib [Kyprolis]-based regimen and an ixazomib [Ninlaro]-based regimen. We’re talking about the second relapse, so the anti-BCMA [B-cell maturation antigen] therapies and CAR [chimeric antigen receptor] T-cell therapy are not there yet. Ultimately, what is the goal for this line of therapy? What are you trying to obtain? Better, deeper, and longer responses? What are your considerations about the kidney function, about the high-risk cytogenetics, the safety, the toxicity, the tolerability?

AHSAN SHAH, MD: I agree…regarding doing carfilzomib. I was thinking of a selinexor [Xpovio]/carfilzomib combination as a potential option.

GRAJALES-CRUZ: Absolutely. It’s interesting that you picked that combination because both carfilzomib and selinexor have been studied, especially in the high-risk population.¹ It’s a pretty appealing combination for a patient such as this one. We have to keep in mind that this patient is relatively young because we’re talking about 72 to 73 years of age for multiple myeloma. That [young] for the most part, especially with the population that we see here in Florida, which is becoming elderly. She has a great performance status besides her kidney function, but we can adjust the doses as necessary.

What about cost reimbursement and quality of life? Because, ultimately, we know that we’re dealing with an incurable disease. Quality of life has a big role to play in the way that we select the agents that we give to our patients. Is that a consideration for you? Does the oral approach versus intravenous versus subcutaneous shots play any role in your rationale?

JORGE HURTADO, MD: Like you were mentioning, for most of these patients, once you hit third line or so, we’re [essentially] managing the disease. I think of sequencing strategies rather than [giving] them a 3-drug regimen or anything like that. There are always exceptions, but in this patient I will probably prioritize oral [administration], which is easier to take, etc. A clinical trial for this particular patient is not a bad idea either, especially we can use some of the newer medication a little bit earlier like BCMA-directed therapy.

GRAJALES-CRUZ: Absolutely. The [idea] that you bring to the table about clinical trials is right on point. That is how we got much better at treating multiple myeloma. Twenty years ago, the survival in somebody with newly-diagnosed multiple myeloma was 2 to 3 years. Now we can have a very different conversation with our patients. Granted, it’s still an incurable malignancy; it’s incurable but treatable, to some extent. Some patients will run out of gas and eventually the disease will take over but it’s no longer that 2 to 3 year overall survival for those patients, and clinical trials have played a big role into changing that. That is obviously something that we encourage tremendously.

CASE UPDATE

The patient was started on selinexor plus bortezomib and dexamethasone based on her worsening renal impairment, del17p status, and prior therapies​​. She achieved VGPR​.

GRAJALES-CRUZ: This patient was started on selinexor/bortezomib/dexamethasone, and this took into consideration several factors; the renal impairment, the high-risk disease, and the prior therapies. This patient tolerated bortezomib very well and that toleration is something also that we have to account for at the time of making the decision for treatment. This patient…achieved a VGPR.

[Based on a poll], it seems that a big portion, close to 80% of us, have used selinexor in this population. Dr Shah mentioned the combination of selinexor/carfilzomib/dexamethasone. Is anybody else using a different combination for selinexor? Is anyone using selinexor with bortezomib, with an IMiD [immunomodulatory imide drug], or with a CD38-[targeted antibody]?

JAY WANG, MD:I used it a long time ago as a single agent in penta-refractory patients. I’ve not used it recently, but I think if the trial data looks better with either bortezomib or daratumumab, I may consider using it. But my experience is very limited, just as penta-refractory [treatment] in a couple of patients but I didn’t have good luck with it. With the new dose adjustments, I think it should be more tolerable so I’m willing to give it a try.

GRAJALES-CRUZ: Out of curiosity, do you remember what schedule and dose were you using?

WANG: It was 160 mg or 120 mg twice-a-week dosing at that time.

GRAJALES-CRUZ: The twice-a-week dose, the intense one.

WANG:Now the dosing is different.² I have not used the new dosing or in combination, but I will consider it in the near future if I have the right patients.

GRAJALES-CRUZ: Is anybody else using selinexor nowadays maybe as a bridge to CAR T-cell therapy, prior to CAR T-cell therapy, or in different combinations, or patients that simply want to do oral [therapy]?

UDAY DANDAMUDI: I have 1 patient currently getting selinexor and pomalidomide as a bridge to CAR T-cell therapy with the once-a-week schedule.

GRAJALES-CRUZ: Did you start at 100 mg, 80 mg, or 60 mg?

DANDAMUDI: I started at 80 mg. They did really well. Initially I started olanzapine [Zyprexa] for prophylaxis, but the patient was getting drowsy, so I stopped the olanzapine and he’s doing very good without any regular antiemetic regimen.

GRAJALES-CRUZ: Perfect.

_References:

_{1. Gasparetto C, Schiller GJ, Tuchman SA, et al. Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients. Br J Cancer. 2022;126(5):718-725. doi:10.1038/s41416-021-01608-2}

_{2. Xpovio. Prescribing information. Karyopharm Therapeutics; 2020. Accessed July 26, 2023. https://tinyurl.com/2989n4ua}