Axicabtagene Ciloleucel in patients with refractory large B Cell lymphoma

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Published: 6 Dec 2018
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Dr Frederick Locke - Moffitt Cancer Centre, Tampa, USA

Dr Frederick Locke speaks to ecancer at ASH 2018 about the use of axicabtagene ciloleucel in patients with refractory large B cell lymphoma.

He explains that refractory large B cell lymphoma patients have very poor prognosis but that the use of axicabtagene ailoleucel kept 39% patients in remission for a median of 27 months.

Dr Locke adds that this 2 year point is very important in large cell lymphoma as it has been seen that patients who reach this point in remission have a good chance of the lymphoma not returning.

ZUMA-1 was a multi-centre trial testing out axicabtagene ciloleucel which is a CD19 directed CAR T-cell therapy for patients with refractory diffuse large B-cell lymphoma and some of its variants. These are patients that didn’t respond to their last line of chemotherapy or had relapse within twelve months of a prior autologous haematopoietic stem cell transplant. We know from historical data these patients have a very poor prognosis – they have a 25% or one in four chance of having a response to standard chemotherapy and a one in ten chance of getting a CR. So we tested out axi-cel, as we call it, short for axicabtagene ciloleucel, in these same patients. We previously reported the results of the phase I and then the phase II pivotal portion of the trial and we’re here at ASH to give an update on the results and really look at the durability of the therapy.

The therapy is durable. What we’ve presented here at ASH and also simultaneously published in the Lancet Oncology is that 39% of the patients who received an infusion of axicabtagene ciloleucel 39% remain in ongoing remission at a median of over 27 months. So all patients had at least two years of time for follow-up; beyond two years almost 40% of patients have no reappearance of their lymphoma. That’s remarkable – again, these are patients that had very little chance for response with standard chemotherapy and now they have ongoing responses at two years. Even more remarkable is that we know the two year time point is very important in large cell lymphoma and that’s because of data in patients who got up-front chemotherapy – if they are in remission two years later those patients have a very good chance of their lymphoma never coming back, five years and ten years. Similarly patients who are in remission two years after an autologous haematopoietic stem cell transplant – two years after a transplant in remission predictive of ongoing remission. So now we’re seeing at that same two year time point that 40% of these patients without really any other options are in remission. It’s pretty remarkable. We believe and we hope that their lymphoma may never come back.

What is the take home message?

The take home message is that this therapy can work, it really can work and it’s really important to get patients referred quickly so that they can get the therapy as soon as possible. Patients who have had three lines, four lines, five lines of therapy, the more lines they have the harder it is to get them in to have the cells collected and manufactured. There’s also other data here at ASH that shows that it can be given off trial in the real world. I think that’s really important to understand that this trial data is really exciting but in fact we’re able to give these therapies as a standard of care treatment to the patients who need it and really impact lives.