Hill Welcomes Addition of Selinexor to DLBCL Armamentarium

The recent approval of selinexor (Xpovio) provides a novel treatment for patients with diffuse large B-cell lymphoma (DLBCL) who have exhausted available options, said Brian T. Hill, MD, PhD, who added that the agent can be well tolerated with the right supportive care measures.

On June 22, 2020, the FDA approved the XPO1 inhibitor for the treatment of patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.

The approval is based on findings from the phase 2b SADAL trial (NCT02227251), in which selinexor elicited a 29% overall response rate (95% CI, 22%-38%) and a complete response (CR) rate of 13% in patients with DLBCL.

Additionally, of the 39 patients who achieved a CR or partial response, 38% experienced response durations of at least 6 months and 15% had response durations that lasted at least 1 year.

Responses were seen in both germinal center B-cell (GCB) and non-GCB DLBCL subtypes.

Serious adverse effects (AEs) occurred in 46% of patients, most often from infection. Thrombocytopenia was the leading cause of dose modifications. Additionally, 80% of patients developed gastrointestinal toxicity, 61% developed any-grade hyponatremia, and 25% experienced central neurological AEs.

“With attention to supportive care, selinexor is a good option for patients with relapsed disease who have exhausted other treatment options, as it may lead to durable remissions,” said Hill.

In an interview with OncLive, Hill, director of the Lymphoid Malignancies Program and a staff physician at the Taussig Cancer Institute of Cleveland Clinic, discussed the clinical implications of the FDA approval of selinexor in relapsed/refractory DLBCL.

OncLive: How will the approval of selinexor impact the paradigm for patients with relapsed/refractory DLBCL?

Hill: The approval of selinexor for patients with DLBCL gives us another treatment option for patients who have exhausted other therapies. This is an oral agent, which differentiates it from intravenous therapies. It is also less cumbersome than CAR T-cell therapy, for instance, which requires hospitalization. These patients often run out of options, so selinexor is a welcomed addition.

Do you anticipate that the drug will be used in all patients with DLBCL, regardless of subtype?

On the registrational SADAL trial, which led to the FDA approval of selinexor, there were equal responses in GCB and non-GCB [subtypes], with a numerical trend toward greater responses in the GCB subtype. It’s not anticipated that there will be 1 subgroup that does not respond as well with this agent.

What do we know about selinexor from our experience with the agent in multiple myeloma?

Selinexor is FDA approved for patients with multiple myeloma. It is an oral agent that acts by inhibiting nuclear export factors. [That inhibition] leads to the altered accumulation of transcription factors and other mediators within the nucleus and, ultimately, cell death.

Could you elaborate on the data from the SADAL trial that served as the basis for the approval in DLBCL?

SADAL is a single-arm, phase 2 clinical trial of patients with relapsed/refractory DLBCL who had failed several lines of prior therapy. Patients were administered oral selinexor twice weekly at different doses of either 60 mg or 100 mg.

Notable toxicities, particularly at the higher dose, were nausea, anorexia, diarrhea, and fatigue.

The approved dose is 60 mg twice weekly. With adequate and appropriate supportive care such as antiemetics and other considerations, patients can stay on this drug for long periods of time.

Are there other supportive care measures besides antiemetics that you recommend?

Antiemetics are the big one, but other [measures] are also sometimes used. These include medications that we don’t typically think of as supportive care for patients undergoing most lymphoma treatments such as appetite stimulants. These can sometimes help patients overcome the anorexia and weight loss that is sometimes seen with this agent.

Can supportive care be managed by patients at home, especially during the coronavirus disease 2019 (COVID-19) pandemic?

Now that we’re in the COVID-19 pandemic—which is not going away anytime soon—there is some interest in avoiding infusions that require the patient to come into the clinic. However, it is still important to monitor patients who are receiving selinexor or any other treatment. There could be cytopenias, including thrombocytopenia, with selinexor that need to be monitored. The patient needs to have laboratory tests done for monitoring purposes. If they’re going to have virtual visits, they do not necessarily have to come into the infusion center for treatment.

What is your take-home message to your colleagues regarding this approval?

The big opportunity for this agent is in its administration and potential for long-term use. Although the toxicities can sometimes be difficult to manage without adequate supportive care, on the study many patients achieved remission. [Moreover], some patients were able to maintain a CR for over 2 years on continuous oral dosing.

Reference

FDA approves selinexor for relapsed/refractory diffuse large B-cell lymphoma. News release. FDA. June 22, 2020. Accessed June 23, 2020. bit.ly/37VnEXd.