EBMT 2024 | CAR-T therapy as the SoC in 2L LBCL and barriers that remain

So I think that now we all are trying to get our patients to second line CAR-T if they’ve had an early relapse from their first line treatment. And I think that we’ve recognized this now from studies looking at both axi-cel and liso-cel in a second line space for those early relapses, showing that there is a significant improvement in outcomes for these patients. So within the session, we were not only looking at why we deliver, so looking at the data, but also looking at how we deliver second line CAR-T. So talking about the importance of holding therapies, for some patients the kinetics of disease are so aggressive that we have to give them some holding chemotherapy. So the case I presented, we needed to give an urgent cycle of GDP. Also talking about bridging treatment to try and reduce total metabolic tumor volume, again using either chemotherapy or radiotherapy. So there was a lot of discussion about patient selection, about the pathway, about trying to get our patients to infusion because of that improvement if we give them second line CAR-T as opposed to autologous stem cell transplant, if they’re an early relapser.

So when we’re thinking about the barriers to CAR-T, it’s about timing and trying to make sure we’re keeping the patient as well as possible while the CAR-Ts are being manufactured. And also about patient selection. And I think that what was quite helpful was that we also had a patient with us in this session talking about the difficulties they found with the CAR-T process, and a lot of that was about coping with the uncertainty and unpredictability and certainly reassurance, and recognizing that these symptoms of concern were very normal for a patient really came came across. So I think that we need to make sure that as soon as a patient has not responded to their first line treatment, that we refer them urgently for CAR-T treatment.

There was some discussion about whether we should be scanning all patients at 11 months, for example, so that we don’t miss the opportunity of making sure those early relapses so relapsing within 12 months actually obtain CAR-T. In my practice I don’t, I see them at 11 months if they have any concerning symptoms at all, I do have a low threshold to scan, but I think that we would be doing a lot of unnecessary scans for all patients if we scanned everybody at 11 months.

So I think careful follow up in that first year, making sure we’re not missing those early relapses, rapid referral identification and getting them an apheresis slot. Careful bridging. We’re using a lot of radiotherapy bridging now second line and and sometimes GDP sort of high dose chemotherapy second line for our bridging. And then obviously reinfusion as soon as those cells are available whilst the patient is well. So I think that we’re getting more experience of using second line CAR-T, and it’s certainly our standard of care for these early relapsing patients.