Selinexor Triplet Reviewed as Second-Line Option in Multiple Myeloma

Jack Khouri, MD​

Assistant Professor, Department of Medicine

Lerner College of Medicine of Case Western Reserve University

Associate Staff, Hematology and Medical Oncology

Taussig Cancer Center

Cleveland Clinic​

Cleveland, OH

CASE SUMMARY

• A 76-year-old man was diagnosed with multiple myeloma (IgG-kappa)​ 5 years ago.
• Hypertension, well controlled with lisinopril​
• He noticed a progressive decline in his stamina, and presented 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 with a complete response​.

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Three years later​

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

Targeted Oncology: What trial data would you consider relevant for a patient such as this?

JACK KHOURI, MD​: The BOSTON study [NCT03110562] looked at selinexor [Xpovio] in the early relapse setting, so 1 to 3 lines of therapy in 402 patients.¹ This was a phase 3 trial with 2 arms: selinexor, bortezomib [Velcade], dexamethasone [SVd] vs bortezomib and dexamethasone [Vd]. Bortezomib was given differently in the second arm; in the Vd arm, it was given biweekly. The primary end point was progression-free survival [PFS]. Patients were stratified based on whether they had [prior] bortezomib. More than half of the patients were…over 65 years of age, and less than 20% had high-risk disease with Revised International Staging System stage III.

The baseline characteristics between the arms were well balanced. Deletion 17p was found in 11% on the SVd arm [n = 195] and 8% on the Vd arm [n = 207]. Most of the patients had 1 line of therapy, so most of the patients were in that first relapse setting.... Most of the patients had received bortezomib before so a lot of those patients had VRd [bortezomib, lenalidomide (Revlimid), dexamethasone] initially, or some bortezomib-based regimen in their frontline setting, which is a little bit different from the case that we have. But that tells you that a lot of those patients had bortezomib before they got selinexor and bortezomib in this study. Not many of them had daratumumab; only 6% receiving SVd and 3% receiving Vd had daratumumab. But the majority had bortezomib before they enrolled on study.

What was the efficacy seen with SVd in the BOSTON trial?

There was definitely a PFS advantage to adding selinexor to bortezomib and dexamethasone, with the median PFS being 13.93 months for SVd vs 9.46 months for Vd with an HR of 0.70 [95% CI, 0.53-0.93; P = .0075]. So there was a decreased risk of death or progression by 30% for the triplet. I think this is a really good PFS in this in this setting, especially in a population who had received bortezomib before. This tells me that patients can be sensitive again to bortezomib if you add selinexor to it, although they had it before their first relapse.

Objective response rates were 76.4% with SVd and 62.3% with Vd, so the responses were higher with the triplet arm.² The median time to response was approximately 1 month in both arms, and the median duration was longer in the SVd arm, so 20.3 months vs 12.9 months [with Vd].

Subgroups such as cytogenetics, prior daratumumab, renal impairment, age, and prior bortezomib did impact outcomes.¹ The addition of selinexor…worked in all of the patients regardless of cytogenetics. Patients with high-risk cytogenetics did better when you added selinexor. Patients who were older had better median PFS with the addition of selinexor. It looked like the addition of selinexor helped all of the subgroups that were enrolled on this study.

Looking at adverse events [AEs] with SVd, the majority were hematologic. Thrombocytopenia was very common; 60% of patients had any-grade thrombocytopenia [on the SVd arm]. Approximately one-third had any-grade anemia, and any-grade neutropenia was 15%. Fatigue of any grade was common at 42%. Gastrointestinal AEs were common; half of the patients had any-grade nausea. About one-quarter of the patients had any-grade weight loss, and decreased appetite was also seen in about one-third at any grade. There was a significant number of patients who needed dose modification on the study [treatment-related AE discontinuation, 21% with SVd vs 16% with Vd].

REFERENCES:

1. 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

2. Dimopoulos MA, Delimpasi S, Simonova M, et al. Weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in patients with multiple myeloma (MM) after one to three prior therapies: Initial results of the phase III BOSTON study. J Clin Oncol. 2020;38(suppl 15):8501. doi:10.1200/JCO.2020.38.15_suppl.8501