The Pros and Cons of Selinexor (Xpovio)
- Selinexor (Xpovio) was FDA-approved in June 2020 for diffuse large B-cell lymphoma that has returned or that hasn’t responded to two other treatments
- Studies find that about 30% of people who take this drug respond to it, and 13% have a complete response
- Xpovio can cause side effects such as nausea, fatigue, and low blood cell counts
In June 2020, the FDA approved the drug selinexor (Xpovio) to treat diffuse large B-cell lymphoma that has come back or that hasn’t responded after at least two other treatments. For people whose cancer is proving stubbornly resistant to treatment, this approval offers yet another option to try. And, it works in a new way.
“It is a drug that targets a pathway the cancer cells rely on, that the normal cells don’t use as often,” Dr. Catherine Diefenbach, hematologist/oncologist at NYU Langone Health, tells SurvivorNet. “And it interrupts an important pathway that the lymphoma cells use for survival and proliferation.”
Essentially what this drug does is to block a protein called XPO1 that enables cancer cells to move harmful substances out of their nerve center — the nucleus. If they can’t remove these harmful substances, it’s harder for the cancer cells to survive.
The Risks
The study that got Xpovio approved, called SADAL (pronounced “saddle”), tested out this drug in 267 people with relapsed and refractory (treatment-resistant) diffuse large B-cell lymphoma. Participants took a 60-milligram pill twice a week until either their cancer progressed or they developed unacceptable side effects — which turned out to be a noteworthy problem.
“My concerns about this study are really that there was a significant amount of gastrointestinal toxicity,” Dr. Diefenbach says. “A large number of patients had nausea and diarrhea.”
“Nausea needs to be managed aggressively,” adds Dr. Jakub Svoboda, medical oncologist at Penn Medicine. Selinexor may also lower blood counts, he says, which may require dose modifications.
Fatigue was another issue, with almost two-thirds of people in the study complaining about feeling tired. “These are already patients with relapsed lymphoma and they’re taking on quite a significant symptom burden, potentially, from their therapy on top of their lymphoma,” Dr. Diefenbach adds.
Other side effects from this drug include:
- Diarrhea
- Appetite loss and weight loss
- Increased risk for infection
- Dizziness, fainting
- Reduced alertness
Are the Rewards Worth the Side Effects?
These types of side effects would be “forgivable,” Dr. Diefenbach says, if the drug had very positive effects on the cancer. But less than a third of the study participants responded to Xpovio, and only 13% — about one in five people — had a complete response.
“Generally, in terms of lymphoma therapy, particularly aggressive lymphoma, the only meaningful responses are complete responses because these are the only patients who are going to have long-term disease control,” Dr. Diefenbach says.
However, “It is encouraging that some patients, including those who failed previous treatments, had very long responses over 12 months,” adds Dr. Svoboda.
What the Future Might Hold for Xpovio
It’s possible that combining Xpovio with another drug would allow doctors to lower the dose enough to prevent some of the side effects, Dr. Diefenbach tells SurvivorNet. “The symptoms will not be as severe, and it would be a good combination partner.” But she says that if you’re considering taking Xpovio on its own, you might be better off enrolling in a clinical trial of a new drug that could have fewer side effects.
It’s important to note that Xpovio hasn’t been used extensively yet in medical practice. Larger trials will be needed to learn more about the benefits and risks of this drug, Dr. Julie Vose, professor of internal medicine in the Division of Oncology & Hematology at University of Nebraska Medical Center, tells SurvivorNet.
Despite its drawbacks, Xpovio offers a new non-Hodgkin lymphoma treatment. “What is exciting is that we now have another drug approved for relapsed large-cell lymphoma,” Dr. Diefenbach syas. “And so this gives our large-cell lymphoma patients yet another option for therapy.”
Reviewed by Dr. Sairah Ahmed, associate professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Learn more about SurvivorNet's rigorous medical review process.
Dr. Catherine Diefenbach is a hematologist–oncologist specializing in the care of patients with lymphoma. She is director of hematology translational research, and director of the Clinical Lymphoma Program at NYU Langone’s Perlmutter Cancer Center. Read More
The Pros and Cons of Selinexor (Xpovio)
- Selinexor (Xpovio) was FDA-approved in June 2020 for diffuse large B-cell lymphoma that has returned or that hasn’t responded to two other treatments
- Studies find that about 30% of people who take this drug respond to it, and 13% have a complete response
- Xpovio can cause side effects such as nausea, fatigue, and low blood cell counts
In June 2020, the
FDA approved the drug selinexor (Xpovio) to treat
diffuse large B-cell lymphoma that has come back or that hasn’t responded after at least two other treatments. For people whose cancer is proving stubbornly resistant to treatment, this approval offers yet another option to try. And, it works in a new way.
“It is a drug that targets a pathway the cancer cells rely on, that the normal cells don’t use as often,” Dr. Catherine Diefenbach, hematologist/oncologist at NYU Langone Health, tells SurvivorNet. “And it interrupts an important pathway that the lymphoma cells use for survival and proliferation.”
Read More
Essentially what this drug does is to block a protein called
XPO1 that enables cancer cells to move harmful substances out of their nerve center — the nucleus. If they can’t remove these harmful substances, it’s harder for the cancer cells to survive.
The Risks
The study that got Xpovio approved, called SADAL (pronounced “saddle”), tested out this drug in 267 people with relapsed and refractory (treatment-resistant) diffuse large B-cell lymphoma. Participants took a 60-milligram pill twice a week until either their cancer progressed or they developed unacceptable side effects — which turned out to be a noteworthy problem.
“My concerns about this study are really that there was a significant amount of gastrointestinal toxicity,” Dr. Diefenbach says. “A large number of patients had nausea and diarrhea.”
“Nausea needs to be managed aggressively,” adds Dr. Jakub Svoboda, medical oncologist at Penn Medicine. Selinexor may also lower blood counts, he says, which may require dose modifications.
Fatigue was another issue, with almost two-thirds of people in the study complaining about feeling tired. “These are already patients with relapsed lymphoma and they’re taking on quite a significant symptom burden, potentially, from their therapy on top of their lymphoma,” Dr. Diefenbach adds.
Other side effects from this drug include:
- Diarrhea
- Appetite loss and weight loss
- Increased risk for infection
- Dizziness, fainting
- Reduced alertness
Are the Rewards Worth the Side Effects?
These types of side effects would be “forgivable,” Dr. Diefenbach says, if the drug had very positive effects on the cancer. But less than a third of the study participants responded to Xpovio, and only 13% — about one in five people — had a complete response.
“Generally, in terms of lymphoma therapy, particularly aggressive lymphoma, the only meaningful responses are complete responses because these are the only patients who are going to have long-term disease control,” Dr. Diefenbach says.
However, “It is encouraging that some patients, including those who failed previous treatments, had very long responses over 12 months,” adds Dr. Svoboda.
What the Future Might Hold for Xpovio
It’s possible that combining Xpovio with another drug would allow doctors to lower the dose enough to prevent some of the side effects, Dr. Diefenbach tells SurvivorNet. “The symptoms will not be as severe, and it would be a good combination partner.” But she says that if you’re considering taking Xpovio on its own, you might be better off enrolling in a clinical trial of a new drug that could have fewer side effects.
It’s important to note that Xpovio hasn’t been used extensively yet in medical practice. Larger trials will be needed to learn more about the benefits and risks of this drug, Dr. Julie Vose, professor of internal medicine in the Division of Oncology & Hematology at University of Nebraska Medical Center, tells SurvivorNet.
Despite its drawbacks, Xpovio offers a new non-Hodgkin lymphoma treatment. “What is exciting is that we now have another drug approved for relapsed large-cell lymphoma,” Dr. Diefenbach syas. “And so this gives our large-cell lymphoma patients yet another option for therapy.”
Reviewed by Dr. Sairah Ahmed, associate professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Learn more about SurvivorNet's rigorous medical review process.
Dr. Catherine Diefenbach is a hematologist–oncologist specializing in the care of patients with lymphoma. She is director of hematology translational research, and director of the Clinical Lymphoma Program at NYU Langone’s Perlmutter Cancer Center. Read More
