In an interview with Targeted Oncology, Michael Schuster, MD, discussed the findings in the phase 2 SADAL study and the importance of the FDA approval of selinexor for the treatment of relapsed/refractory diffuse large B-cell lymphoma.
Selinexor (Xpovio) is now anFDA-approved treatment for patients with relapsed or refractory diffuse large B-cell lymphoma(DLBCL), which received approval based on data from a multicenter, open-label phase 2b study (SADAL, NCT02227251). This recent FDA action makes selinexor the first single-agent and oral therapy available for patients with relapsed/refractory DLBCL, and the only nuclear export inhibitor approved by the FDA for the treatment of 2 different hematologic malignancies, those being multiple myeloma and DLBCL.
In the SADAL study, the agent achieved an overall response rate of 29%, which included complete responses (CRs) in 13% of patients and partial responses (PRs) in 16%, according to findings published in 2019. The responses observed were deep and durable, leading to a median duration of response of 9.2 months (95% CI, 4.8-23.0) in the overall study population and 13.5 months (95% CI, 9.3-23.0) among the group of patients who achieved a CR.
Selinexor also demonstrated positive results in terms of survival, achieving a 9.0-month overall survival (OS) in the overall population (95% CI, 6.2-13.7) after a median follow-up of 11 months. The median OS was not yet reached among patients with a PR or CR.
These results led the study investigators to the conclusion that selinexor has good potential for this patient population.
In an interview with Targeted Oncology, Michael Schuster, MD, director, Bone Marrow Transplant Program, Stony Brook Cancer Center, discussed the findings in the phase 2 SADAL study and the importance of the FDA approval of selinexor for the treatment of R/R DLBCL.
TARGETED ONCOLOGY: What are the options that were available prior to the selinexor approval for patients with relapsed or refractory DLBCL?
Schuster: The good news is that there have been many treatments that have become available over the past couple of years, and there are even more that are currently being studied and will become available. I think the issue is always that there isn't a treatment that is tailored to the individual patient. For example, there may be a patient with relapsed lymphoma for whom the best next option would be a chimeric antigen receptor (CAR) T-cell program. However, there may be patients who are older, less fit, or have many other medical problems going on, and they would not be an ideal candidate for a CAR T-cell clinical trial.
I have an example of patients that I had who were excellent patients for this drug and who benefit from selinexor going forward now that the drug is approved by the. One patient is a woman in her mid-70s who has large cell lymphoma. She was treated with the traditional R-CHOP chemotherapy, then relapsed and received traditional salvage chemotherapy. She then went on to high-dose chemotherapy and autologous [stem cell] transplant (ASCT) but then relapsed within a short period of time after that.
Here's a woman in her 70s who now has had a lot of chemotherapy, has a number of other medical problems going on, and needs some kind of treatment. She was enrolled in the trial, went into complete remission and remains in complete remission on the drug more than a year and a half after starting. This shows that we have all kinds of options for treating these patients.
TARGETED ONCOLOGY: What was the rationale for the SADAL study, and what were the key goals of the study?
Schuster: The rationale is treating patients who have had prior lines of therapy with a drug that has a completely different mechanism of action. In the past, many of us have had patients who've been through chemotherapy and received more chemotherapy and are now refractory to chemotherapy. That was the only option that we had for treating those patients. Also, if patients are refractory to chemotherapy, using another chemotherapy regimen is not going to help.
We were uniformly disappointed with the results of further chemotherapy regimens. Here, we have a drug with a completely different mechanism of action so that we can have the hope that the disease will respond and not develop any resistance mechanisms, which patients might have already developed towards further chemotherapy.
The study was for those kinds of patients who had already been through treatment and now had relapse disease, were not eligible for high-doses of further chemotherapy and ASCT, and to look at progression-free survival in those patients.
TARGETED ONCOLOGY: This study found that selinexor monotherapy induces deep and durable responses in relapsed or refractory DLBCL. Can you elaborate on the efficacy results of this study?
Schuster: The good news is that in this heavily pre-treated population, almost a quarter of those patients had a response to selinexor. These were also patients who went into CR.
CRs went almost 2.2 years without any evidence of progression of the disease. My patient and another patient in the study are 2 examples of that. Here are 2 patients in their 70s with heavily pretreated [disease] who both went into CR and are now approaching 2 years without any evidence of progression.
TARGETED ONCOLOGY: What is most interesting about these data?
Schuster: The most interesting thing is that we have a drug with a very novel mechanism of action. That is something that we can give to patients who've already been through chemotherapy regimens. We now have hope that they can respond to this drug with a novel mechanism of action, and if they do respond that the response has a significant duration.
Also, because it's an oral [agent], it is something that they can take at home rather than having to come into the hospital for intravenous chemotherapy.
TARGETED ONCOLOGY: Can you describe the safety profile of single-agent selinexor, as observed in the SADAL study?
Schuster: I think it's important to recognize that this drug, like every drug, has toxicities. Once they occur, they can be dealt with, but we have to know about them ahead of time. This is something all of us learned during the course of the clinical trial. There were adverse events (AEs) that ranged from nausea and anorexia. There was also asthenia, thrombocytopenia, and hyponatremia.
I think we have to stay closely in touch with patients, use drugs to prevent some of these AEs, and have ongoing conversations with patient to deal with any AEs.
TARGETED ONCOLOGY: Now that selinexor is approved, what impact will this have in the community oncology setting?
Schuster: For most of the patients with relapsed large cell lymphoma who either have failed an ASCT or who are not eligible for ASCT, the options for those patients are limited, especially for patients who are older, unfit, or who have a comorbidity. This is yet another option that we now have for treating those patients.
TARGETED ONCOLOGY: What is most interesting about this approval?
Schuster: I think that this is just the beginning for this drug. As with most of the oncologic drugs it's initially approved as a single agent and then clinical trials develop the drug further in combination with other drugs. This is how we'll start off with the drug, which certainly has a significant response rate is a single agent and now we're in the process of looking at clinical trials of selinexor in combination with other drugs.