Treatment Options for Relapsed/Refractory Diffuse Large B-Cell Lymphoma - Episode 10

SADAL Trial Regimen FDA Approval

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Brian Hill, MD, PhD: The FDA approval for selinexor is anticipated this summer, and it is likely to be approved for relapsed or refractory diffuse large B-cell lymphoma [DLBCL].

The treatment landscape for diffuse large B-cell lymphoma is changing now that we have CAR [chimeric antigen receptor] T-cell therapy. It’s important to know that although a proportion of patients with CAR T cells may be cured, as I mentioned previously, with this therapy, 60% or more of the patients will not enter durable remission and will relapse.

For those patients, there are limited treatment options. Polatuzumab vedotin is a treatment option for those patients in combination with bendamustine and rituximab, which is approved in this setting. It’s anticipated that selinexor will also be approved in this setting.

Andre Goy, MD: This is an oral agent that can be used as a single agent in third-line therapy, as I mentioned, it was just approved. But I think the real benefit will be when we start to combine this with other agents, and hopefully have better disease control.

Julio Chavez, MD, MS: In my opinion, what I look at more is efficacy, how efficacious is a drug or a regimen. For patients with DLBCL, what I typically do is ask them what are their goals, if their goals are to cure the disease, or to maintain the disease in some type of remission, but no cure. If they want to achieve a cure and they’re healthy enough to do it and they don’t have a lot of significant comorbidities, I offer what is the standard of care, which is CAR T-cell therapy. That’s the main thing. I would say with all the CAR T-cell drugs available, essentially, the majority of patients could get CAR T-cell therapy. Age is not a limitation. Our oldest patient was 84 years old, he was in good shape, he was able to get treatment and he’s in remission. I think that’s a reason we have to offer what is the best care and best option, which is a curative option.

If the patient prefers not to undergo CAR T-cell therapy, not only because of the adverse effects, but also because of the logistics—traveling, leaving home, staying in a different place—that’s definitely a factor in deciding whether to pursue CAR T-cell therapy. In those cases in which CAR T cell is not possible for all those reasons, the patient is too weak, too sick, or logistic reasons, then oral agents such as selinexor play a role. Also other agents can be given closer to home, like monoclonal antibodies such as tafasitamab or polatuzumab. Those are viable options in the community.

When you have all these options, you have to choose the option that is more efficacious, but at the same time, less toxic. As I mentioned before, the monoclonal antibodies are used commonly by community oncologists, so they’re familiar with it. I wouldn’t see a problem in using tafasitamab orpolatuzumab. So there are options for those patients and they know how to use them. Selinexor is a novel agent, so you have to try to learn how to manage the adverse effects. Also the activity is modest. I don’t deny there is activity, but it’s not probably the greatest clinical activity, if you compare it to tafasitamab with lenalidomide, or polatuzumab/bendamustine/rituximab.

Finally, the other aspect is the maintenance of an IV [intravenous] line. So far, selinexor is the only oral agent approved for diffuse large B-cell lymphoma in the relapsed/refractory setting as a single agent. That’s definitely convenient because patients just take 1 pill. But again, it’s probably the less important factor in my opinion.

Brian Hill, MD, PhD: One of the things that has come up recently, one of the concerns, is that we’re experiencing the global pandemic of COVID-19 [coronavirus disease 2019]. This has led to some concern about intensive treatment regimens that are highly immunosuppressive, including autologous stem-cell transplantation, and potentially CAR T-cell therapy.

In my mind, the risks and benefits of using immunosuppressive therapy have to be weighed against the risk of infections, including COVID-19. But for a treatment for a disease such as relapsed diffuse large B-cell lymphoma, I think the benefits of the therapies that we discussed, including transplant and CAR T, still outweigh those risks.

There may be patients who are presented with the option of continuing to receive IV therapy as opposed to an oral agent like selinexor that can be taken at home. And it’s possible that an oral agent may be safer because of less exposure to the patient, but it also has to be taken into account that some of these agents can cause neutropenia and even if they’re oral, and that can predispose patients to infection.

Transcript edited for clarity.