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Expert Discusses Latest CAR T-Cell Developments in Non-Hodgkin Lymphoma

Jason Harris
Published: Tuesday, Sep 04, 2018

David Maloney, MD, PhD
David Maloney, MD, PhD
Results in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) suggest that chimeric antigen receptor (CAR) T-cell therapy should be used earlier in treatment, possibly after first relapse, said David G. Maloney, MD, PhD. Administration of these products in earlier lines of therapy could improve outcomes and reduce toxicity, he added.

, Maloney reviewed the latest developments with CAR T-cell therapy in patients with NHL.

OncLive: What is the current state of treatment for DLBCL?

Maloney: DLBCL is a disease where we obviously try to cure it with chemotherapy and that can be remarkably successful in 60% to 70% of patients, but for those who don't go into complete remission or who relapse, then this becomes a life-threatening problem. Standard of care is salvage chemotherapy and, if you have responsive disease, autologous stem cell transplant. Unfortunately, with better therapies including R-CHOP, as the CORAL study showed, our success with transplant has gotten even lower. Therefore, people are very interested in the targeted therapies.

One of the more exciting presentations recently was the polatuzumab vedotin data in combination with bendamustine/rituximab. That seems to be another salvage or bridging therapy where you might be able to get people into a better response. If that's the case, you might be able to use it as a bridging therapy to get to CAR T cells. There are new exciting molecules on the way.

Is CAR T-cell therapy becoming more widespread?

There are 2 products currently approved: tisagenlecleucel and axicabtagene ciloleucel, both targeting CD19. A third [liso-cel] is on the way. These products are different. They have a CAR, but they have different costimulatory domains; 1 is CD28 and the other 2 are 4-1BB. That does cause some differences in the clinic.

These are autologous products. We collect T cells from the patient, then transduce them with a retrovirus—either a gamma virus or an antivirus. These genetically change the cells to express the CAR; they have all targeted CD19 so far. These cells are then given back to patient after lymphodepleting chemotherapy. These have led to very high response rates—up to 80% in 3 of the large phase II trials that have been done. The results led to FDA approvals for 2 agents.

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