Treatment Options for Relapsed/Refractory Diffuse Large B-Cell Lymphoma - Episode 12

Relapsed/Refractory DLBCL: Unmet Needs

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Brian Hill, MD, PhD: We still have unmet needs for patients with diffuse large B-cell lymphoma. As I mentioned, for older patients in their 80s and above, even standard therapy with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] is very difficult to receive. And in those cases after failure of less intense regimens, such as mini R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], or bendamustine, or others, there is a significant unmet need for patients to be treated with targeted agents. Tafasitamab with lenalidomide is likely to be an option for those patients in the future, as well as selinexor, and polatuzumab vedotin, which is approved in combination with bendamustine/rituximab.

Andre Goy, MD: I think overall in cancer, immunotherapy will continue to expand dramatically. I think more and more we’re going to try to combine small molecules, biological agents as sort of an induction with or without immunotherapy, and immunotherapy afterward as a consolidation. That’s 1 model. But there’s also lymphoma—more and more we see that we can, as I mentioned for example, the R-squared, ibrutinib window-type trials in the patients who are particularly non-GC [germinal center] subtype and frail patients can respond really well to this and have a shortened version of chemotherapy. And then there are ongoing trials looking at checkpoint inhibitors in combination with chemotherapy. BiTE [bispecific T-cell engager], as I mentioned, combination with trastuzumab, in combination with chemotherapy. More and more we’re going to integrate that.

And the third piece that is important is the role of immunotherapy as an immuno-consolidation post-induction. We know that cell-free DNA might help us with the depth of response in those patients. But we know that the patient’s immune status post-chemotherapy—although we don’t have a great way to quantify it, but based on the ratio data from the Mayo Clinic, for example, the ratio of lymphocytes to monocytes, across the board in a number of diseases and many subtypes of lymphoma—shows that it has a dramatic impact on the outcome. We don’t exactly know yet how to tackle this, but that’s an opportunity as a consolidation eventually. Definitely the question is more novel therapy, more immunotherapy, either in addition or to replace chemotherapy.

Julio Chavez, MD, MS: With the new therapies coming to the clinic, how does cost affect your patients’ access to treatment? I’m sure that cost and access impact a patient’s and oncologist’s decision and, hence, care for therapies, especially for an aggressive disease like diffuse large B-cell lymphoma. Not only the cost of the drug itself, but also the cost of the logistics, such as in CAR [chimeric antigen receptor] T-cell therapy. There is a lot of cost implicated in treating the adverse effects, admission to the hospital, admission to the ICU [intensive care unit], the use of a caregiver, the caregiver has to be off work, the patients cannot drive for 2 months. There is cost in relation to that.

When you talk about the combination of tafasitamab and lenalidomide, I would think that it will be a top price for tafasitamab. But then you have to add the cost of lenalidomide, and whether insurance can cover part of the cost of lenalidomide, there may be a copay for patients. That should be considered in terms of the cost. Tafasitamab is a treatment that is given indefinitely. Patients get treatment for as long as they respond or for as long as they tolerate the medication. So that’s a cost because patients have to keep coming to an infusion center, they have to maintain a line. If they have complications related to the line, like infections or thrombosis, that adds to the cost because we have to treat those conditions. It’s important to consider those.

In the case of selinexor, which is a single oral agent, it will have definitely a top price. It doesn’t have the cost of hospitalization, it doesn’t have the cost of having an IV [intravenous] line. It’s an indefinite treatment, so if there is a patient who had a response, those patients have to remain on the drug for a long time. As far as I remember, in the trial some patients went on treatment for up to 3 years. That should be a consideration in regard to the cost. However, there are other costs that should be considered for selinexor. It’s a novel agent, has specific adverse effects that need to be taken care of, such as diarrhea, nausea, adding the medications to treat the nausea, adding the medications to treat the diarrhea. There are issues with cytopenias as well as thrombocytopenia. There are recommendations in the trial about using growth factors, they also have costs. So it is important to keep in mind when we use the novel therapies available, the other costs that are outside of the specific medications.

Transcript edited for clarity.