ASH 2015

Engineered cells to target multiple myeloma

Dr James Kochenderfer - National Cancer Institute, Bethesda, USA

You’ve been looking at BCMA CAR T-cells. I’d like you to tell me what that is and why it is so exciting, because you’re getting cures in patients with multiple myeloma who have gone through all the available treatments, aren’t you?

Yes. The BCMA stands for B-cell maturation antigen; it is a protein expressed on plasma cells and multiple myeloma is an almost always incurable malignancy of plasma cells. So we wanted to develop a T-cell therapy that could target and eradicate multiple myeloma in patients with advanced treatment refractory myeloma. We’ve treated now twelve patients on a very early dose escalation trial and when we’ve got to the higher doses we’ve had very good responses in some patients. I would not say it’s curative yet, it’s much too early to say that but we have patients who are in stringent complete remission, ongoing, and it’s very exciting because this is the first evidence of T-cells that are able to eradicate large amounts of multiple myeloma and put patients in complete remission.

Can you explain some of the theory of this, these chimeric antigen receptor T-cells? What are they doing in this context?

Chimeric antigen receptor T-cells are T-cells that are genetically modified to target a malignancy. The T-cells can specifically recognise and kill the malignant cells after the genetic modification. So we take the patient’s own cells out of their blood, genetically modify them in the lab and then reinfuse them back into the patient.

And in this study with multiple myeloma where did you get the T-cells from, then? From the patients?

The T-cells are from the patients’ own blood. So the patient with multiple myeloma would come in, undergo an apheresis procedure, which is like giving a blood donation, and that’s where we would get the cells from to work with.

And what happened in the study?

In the study we treated twelve patients. As I mentioned, it was a dose escalation study. In the lower doses the patients did not have responses but when we reached the higher dose levels we’ve seen responses in three of twelve patients, actually, overall. But in the higher dose levels three out of seven patients had responses and the most striking thing was complete eradication of myeloma in two patients. We’ve had one with greater than 80% of their bone marrow taken over by myeloma and another with greater than 90% myeloma. In both cases the patients now have no multiple myeloma in their bone marrow.

This was in patients who had gone through all the treatments, including allotransplant?

No, that’s actually not correct. These patients did not have allotransplants but almost all the patients had autologous transplants and they’d had a large amount of multiple myeloma therapy before.

What might this mean clinically, then, for cancer doctors, do you think, in the future?

I think it’s a completely new and different approach to multiple myeloma treatment. This is a completely different approach, no-one has ever treated multiple myeloma successfully with T-cells before. So particularly it could enhance the treatment of patients with chemotherapy refractory multiple myeloma. We had one patient who had an autologous stem cell transplant and relapsed within three months after that, showing that he was completely refractory to chemotherapy but yet obtained a stringent complete remission on this study.

So what do you think is the brief take-home message?

I think this is a very early but very promising new therapy for multiple myeloma. It opens up a whole new area of CAR T-cell therapy for multiple myeloma. Strikingly it was very effective in a similar manner to what we’ve seen with the anti-CD19 CAR T-cell therapies which have been much more extensively studied.

Could you potentially bring it earlier in the disease process?

Potentially but I think that’s years away.