Immuno-Oncology Resource Center
Immuno-Oncology Resource Center
January 13, 2020
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‘Immunotransplant’ shows potential for non-Hodgkin lymphoma

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Joshua Brody

A combination of immunotherapy and stem cell transplantation could benefit patients with treatment-resistant non-Hodgkin lymphoma, according to preclinical data published in Cancer Discovery.

The laboratory research findings prompted initiation of a clinical trial to study the approach — which has improved the success of immune checkpoint blockade in lung cancer and melanoma — among patients with advanced-stage non-Hodgkin lymphoma.

“Using immunotransplant to enhance the efficacy of checkpoint blockade therapy could be broadly significant as these immunotherapies are a standard therapy for melanoma, kidney cancer, lung cancer and others,” Joshua Brody, MD, director of the lymphoma immunotherapy program at Tisch Cancer Institute at Mount Sinai and a HemOnc Today Next Gen Innovator, said in a press release. “Even for settings in which checkpoint blockade therapy proves ineffective, our data suggest that its efficacy may be ‘rescued’ by immunotransplant. This research also suggests that the addition of checkpoint blockade may improve other T-cell therapies, such as chimeric antigen receptor T-cell therapy.”

Healio spoke with Brody about the preclinical study, the human trial underway and what he hopes future research will show.

Question: How did the idea for this approach come about and how does it work ?

Answer: We saw a need for improvement for these patients. These immunotherapies have shown efficacy in other cancer types, so we thought it may be important to test this among patients with non-Hodgkin lymphoma. We know that T-cell therapies wipe out T cells and put new T cells into the patient’s body, then the new cells proliferate to fill up the space. This idea has been around for a long time, but more and more we realize how important of a “gas pedal” this is for T cells.

Q: Can you elaborate on the preclinical work and what you found?

A: When this immunotherapy is combined with a stem cell transplant, which we dubbed immunotransplant, the process ramps up the T cells to increase the cancer-killing immune response 10-fold, allowing it to be effective for non-Hodgkin lymphoma and more successful for melanoma and lung cancer. The immunotransplant therapy was much more effective than immune checkpoint blockade alone in the lab. Immune checkpoint blockade alone conferred almost zero benefit in most of the tumor types we tested. However, when we combined it with immunotransplant, it sometimes made the mice live much longer and cured a significant proportion of the tumor types (around 40%).

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Q: Can you talk about the human trial underway based on the preclinical study findings?

A: We brought forth this immunotransplant therapy for patients with advanced non-Hodgkin lymphoma or diffuse large B-cell lymphoma. We are giving patients two doses of combination therapy and then we take out their T cells and place them in the freezer. We give them therapy to make space for T cells to be reinfused into their body and then the immunotransplant happens a couple of days later.

Q: What do you hypothesize that you will find?

A: We have treated a small number of patients so far. One patient had relapsed/refractory DLBCL and was requiring narcotic pain medicine multiple times per day. We treated her with immunotransplant and she has been in complete remission for more than 1 year. There is some hint that this treatment works well, but these are only preliminary results, and we expect final results of this study in a couple of years.

Q: Is there anything else that you would like to mention?

A: In the paper, we also studied lung cancer and melanoma. Both are cancers that we treat with the standard therapy, and the whole point of this paper is that immunotransplant makes that therapy more effective. Thus, it seems like an obvious next step to treat patients with this combination to see if it is as effective as it was in the laboratory in our preclinical research. This is translatable science. – by Jennifer Southall

For more information:

Joshua Brody, MD, can be reached at Icahn School of Medicine at Mount Sinai, 1470 Madison Ave., New York, NY 10029; email: joshua.brody@mssm.edu.

Disclosures: Brody reports no relevant financial disclosures.