In diffuse large B-cell lymphoma the current standard of care treatment is a combination chemotherapy and for patients who respond to that chemotherapy they go on to get an autologous haematopoietic stem cell transplant. We know with that treatment paradigm that only a few patients are cured of their lymphoma. Overall in the second line only about 10% are cured because patients either aren’t eligible for a transplant or they don’t respond to chemotherapy or progress before they can get the transplant. So the ZUMA-7 trial is the world’s first randomised global multicentre phase III randomised trial testing out CAR T-cell therapy, in this case axicabtagene ciloleucel, against that second line treatment paradigm, chemo followed by transplant.
What was the design of the trial?
The trial was designed for a one-to-one randomisation of CAR T versus patients who would get the standard of care which was investigator-selected, protocol-defined combination chemotherapy regimen and if the patient responded after two or three cycles they’d go on to get high dose chemotherapy and consolidative autologous transplant. The primary endpoint was event free survival with events defined as death due to any cause, progression or a change in therapy. Key secondary endpoints include the objective response rate and overall survival, which we’ve just done an interim analysis of overall survival at this point.
What were the key findings?
The first key finding is that of the patients randomised to the standard of care only 36% were able to make it all the way through to autologous haematopoietic stem cell transplant as compared to CAR T-cell therapy of which 94% of patients were able to receive axicabtagene ciloleucel. So if we’re talking about the definitive therapy quite a few more patients received axi-cel as compared to autologous transplant.
The primary endpoint was event free survival and the endpoint was met. This CAR T-cell therapy was clearly better, it’s clearly better than the standard of care in terms of event free survival with a median event free survival of over 8 months for axi-cel and 2 months for the standard of care. Even more important, at two years, so the two-year estimate of event free survival with axicabtagene ciloleucel was 41% as compared to 16% with the standard of care. So what that means is that two years after randomisation 41% of patients randomised to axi-cel can expect to be in remission, not need additional therapy, not have had additional therapy, as compared to 16% in the standard of care arm.
So pretty remarkable results and then, finally, the response rates are much higher in fact. The complete response rates are double that with axi-cel as compared to that standard second-line treatment regimen. So pretty remarkable results.
What could be the clinical implications of these results?
The clinical implications are that for patients who relapse following frontline chemotherapy, especially those within twelve months which is one of the eligibility criteria, they should have the opportunity to get axicabtagene ciloleucel as the very next treatment for second line large B-cell lymphoma. So this is important findings and we like to give the best therapy up front.
What’s important for community oncologists and those out in the community to understand is that in order to get this therapy they have to be referred and referred quickly. So think of a CAR T-centre as soon as the patient is progressing on frontline therapy.