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BSH 2022 | New data on DLBCL in the UK and its impact on treatment decisions

In this video, Wendy Osborne, MBBS (Hons), MRCP, FRCPath, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK, gives an overview on new data in diffuse large B-cell lymphoma (DLBCL) and how this may influence current and future treatment decisions. Dr Osborne first discusses factors that are currently changing treatment practice, drawing focus on the benefits of using bone prophylaxis and CNS prophylaxis in high-risk patients. Following this, Dr Osborne discusses the exciting results from the POLARIX study (NCT03274492), investigating the use of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in patients with previously untreated DLBCL. Finally, Dr Osborne discusses how identifying high-risk patients upfront and using novel agents including chimeric antigen receptor T-cell (CAR-T) therapy in the frontline setting may improve patient outcome, as seen in the ZUMA-12 study (NCT03761056). This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.

Transcript (edited for clarity)

There’s been quite a lot of new data over the last year for diffuse large B-cell lymphoma. And I like to think about it, about what can change practice now and what possibly in the near future and what is a hope for the further future in terms of change. And really probably what’s changed practice now is I think many more of us are using bone prophylaxis for our patients. We know that our patients receive high doses of steroids...

There’s been quite a lot of new data over the last year for diffuse large B-cell lymphoma. And I like to think about it, about what can change practice now and what possibly in the near future and what is a hope for the further future in terms of change. And really probably what’s changed practice now is I think many more of us are using bone prophylaxis for our patients. We know that our patients receive high doses of steroids. We know from previous audit data, that there is a high rate of fracture risk up to about 12%, but there was some data, a randomized study at ASH using bone prophylaxis, showing that it actually improved bone mineral density. So the end point wasn’t fracture. So we don’t know for certain that it’s going to be of benefit, but I think it makes sense that actually, if we recognize that some patients are higher risk, if we can give them bone prophylaxis, as we do in many other forms of medicine, that we should be introducing. So in terms of what’s changing practice now, that is certainly one area.

And then another area where we have new data, where I think that it has changed practice now is CNS prophylaxis because we know that some patients are higher risk than others. And we also know that if patients relapse in their CNS, the outcomes are devastating. The outcomes for secondary CNS lymphoma are very poor, unfortunately. And so we have newer data. So retrospective, international data set of over 2,300 high-risk patients.

Looking at these patients and comparing whether IV methotrexate was better than IT methotrexate or no methotrexate at all. And the conclusion from that study was that actually giving that intravenous methotrexate didn’t reduce relapse risk. But I think that we are all very cautious about how we interpret this excellent dataset, because actually there were only about 400 patients who were high-risk who’d had the IV methotrexate. Many patients only got one dose of IV methotrexate or it wasn’t clear how many doses they had, and what dose intensity.

And also the groups were different. So there were more higher risk groups in the IV methotrexate arm. So I think that what this data has given us is that maybe we just need to have a more careful discussion with our patients. We honestly don’t know the answer, I think, from the data we have. I think that we have a lower threshold maybe to not give the IV methotrexate because it isn’t without toxicity. We know it can put people into renal failure, but maybe for many centers, and certainly where I work, we now don’t give it for patient CNS-IPI of four, and we discuss carefully for those high-risk sites, an IPI of five and six.

But what we also know from the new data is that if we are going to give it, that we should give it at end of treatment because we don’t want to cause any delay in that primary proven R-CHOP treatment. And if we’re going to do it, we should give that IV methotrexate once they have completed it. So I think that these are two areas where we probably have changed or at least discussed change within our own centers, our current management for diffuse large B-cell.

And then thinking about what might change in the near future. And obviously there’s been a lot of excitement following the presentation and publication of the POLARIX study. So the POLARIX study, an excellent randomized double blind placebo controlled Phase III trial with good numbers of patients receiving polatuzumab R-CHP versus standard of care R-CHOP. And there is a progression free survival benefit in the patients who had polatuzumab. And as yet, there hasn’t been an overall survival benefit shown. And I think that this again is leading to a lot of discussions amongst UK clinicians.

If this is approved by NICE, would it be something that we would want to use for our patients? And we definitely want to be discussing this in our BSH special interest group meeting for this, because we know that when a patient with high grade lymphoma relapses, their treatment pathway is intense. If they’re fit enough, they have to have high dose intensive chemotherapy plus an autologous stem cell transplant. So we want to try and avoid those relapses.

And these data show us that there is a reduction in relapse events, but we have to think about the health-economic benefit for our whole NHS as to whether that PFS benefit alone, of about six and a half percent, is enough for us to change UK practice. So I think that that’s sort of a near future discussion.

And then finally, what about further to the future? And for me, I think it’s understanding, trying to pick out those high-risk patients up front. Maybe using a response adaptive approach once we understand the biology better, and then understand their response. So for example, CAR-T frontline, the ZUMA-12 study, picked out what we think are the highest-risk patients upfront and then had an interim PET scan. Many of them were [inaudible 00:05:33] five, so high risk patients, and then introducing CAR-T with much better outcome than we would think. Now, this is early phase data in a clinical trial setting, but this is exciting. And the other thing that was interesting with that is that actually the CAR-T product looked to be superior. So if we can take off those T-cells earlier, it makes sense that there may be less T-cell exhaustion, they may be more effective. So I think that, the future in terms of what else we could add in a frontline setting, who else we can identify as high-risk patients? What about bispecifics? Can we pick out the high-risk patients who could benefit from this or other antibody therapy frontline? So I think in a frontline setting, loads of excitement and lots for us to discuss within our own centers about what we are going to change.

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