Diffuse Large B-Cell Lymphoma (DLBCL)


Xpovio® (selinexor) is a nuclear export inhibitor approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.1

Xpovio received accelerated approval from the US Food and Drug Administration (FDA) for this indication in June 2020 based on the patient response rate, with continued approval dependent on confirmatory trials verifying clinical benefit.1,2

Mechanism of Action

Xpovio is a first-in-class selective inhibitor of exportin 1 (XPO1), also known as CRM1, which is an important nuclear export protein for a number of regulatory proteins, including tumor suppressor proteins (TSPs), oncoproteins, and RNAs. Xpovio uses a process of selective inhibition of nuclear export (SINE), resulting in the nuclear retention of major TSPs, reduction in oncoproteins, and induction of cell-cycle arrest and apoptosis, which results in the selective elimination of tumor cells while sparing normal cells.3,4

Xpovio demonstrated tumoricidal activity in preclinical models of several cancer types.5-7

Read more about DLBCL experimental therapies

Administration

Xpovio comes in tablet form to be taken orally on a consistent weekly schedule. The recommended dosage of Xpovio for patients with DLBCL is 60 mg on Days 1 and 3 of each week until disease progression or unacceptable toxicity.1

It is recommended to administer a 5-HT3 receptor antagonist and other anti-nausea agents prior to and during treatment. Patients should also maintain consistent fluid and caloric intake levels during treatment to prevent dehydration and weight loss.1

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Adverse Reactions

The most common adverse reactions, with an incidence ≥20%, in patients with DLBCL are fatigue, decreased appetite, weight loss, nausea, vomiting, diarrhea, constipation, and pyrexia.1

Warnings and Precautions

Warnings associated with Xpovio administration include thrombocytopenia, neutropenia, gastrointestinal toxicity (nausea, vomiting, diarrhea, anorexia, weight loss), hyponatremia, serious infection, neurological toxicity (including dizziness and mental status changes), embryo-fetal toxicity, and cataracts.1

Platelet counts should be monitored throughout treatment with Xpovio to manage possible thrombocytopenia. In addition, neutrophil counts should be monitored throughout treatment to manage neutropenia if it develops. Antiemetic prophylaxis can be provided for gastrointestinal toxicity. Hyponatremia can be managed by monitoring sodium levels throughout treatment. Patients are advised to refrain from driving and engaging in hazardous activities until neurological toxicity resolves. Cataracts are treated by surgical removal.1

The drug may cause embryo-fetal toxicity, so effective contraception is advised during treatment with Xpovio and for 1 week after the last dose. Women are also advised not to breastfeed during the same period of treatment and post-treatment due to the potential for serious adverse reactions in breastfed children.1

The safety and efficacy of Xpovio have not been established in children or adolescents.

Get full prescribing information for Xpovio at MPR

Safety and Efficacy in Trials

The efficacy of Xpovio monotherapy was evaluated in a phase 2 study called SADAL (KCP-330-009; NCT02227251),8 a multicenter, single-arm, open-label study including 127 adults with relapsed or refractory DLBCL, not otherwise specified, after at least 2 prior systemic therapies. The study required a minimum of 60 days since the last systemic therapy, or a minimum of 98 days in patients with refractory disease (defined as less than a partial response). Patients received 60 mg of Xpovio orally on days 1 and 3 of each week until the occurrence of disease progression or unacceptable toxicity. The study demonstrated a median overall response rate of 29.1% with a median duration of response of 9.3 months.1,9

The results of this study led to the accelerated approval by the FDA. Many studies are currently underway examining chemoimmunotherapy combinations with Xpovio.

Read more about DLBCL prognosis

References

  1. Xpovio. Prescribing information. Karyopharm Therapeutics Inc; 2022. Accessed August 19, 2022.
  2. FDA approves selinexor for relapsed/refractory diffuse large B-cell lymphoma. US Food and Drug Administration (FDA). June 22, 2020. Accessed August 19, 2022.
  3. Selinexor. National Cancer Institute (NCI)’s Drug Dictionary. Accessed August 19, 2022.
  4. Horesh N, Weiler-Sagie M, Ringelstein-Harlev S. Single agent oral selinexor as a key to potential cure in refractory diffuse large B-cell lymphoma: case report and literature review. Am J Blood Res. 2021;11(1):111-117.
  5. Sun H, Hattori N, Chien W, et al. KPT-330 has antitumour activity against non-small cell lung cancer. Br J Cancer. 2014;111(2):281-291. doi:10.1038/bjc.2014.260
  6. Turner JG, Dawson J, Cubitt CL, Baz R, Sullivan DM. Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents. Semin Cancer Biol. 2014;27:62-73. doi:10.1016/j.semcancer.2014.03.001
  7. Han X, Wang J, Shen Y, et al. CRM1 as a new therapeutic target for non-Hodgkin lymphoma. Leuk Res. 2015;39(1):38-46. doi:10.1016/j.leukres.2014.10.003
  8. Selinexor (KPT-330) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). ClinicalTrials.gov. August 28, 2014. Updated August 15, 2022. Accessed August 19, 2022.
  9. Kalakonda N, Maerevoet M, Cavallo F, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):e511-e522. doi:10.1016/S2352-3026(20)30120-4

Reviewed by Hasan Avcu, MD, on 8/24/2022.

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