VIDEO: Advancements in the treatment of DLBCL

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We are so lucky in DLBCL to make more rapid therapeutic advances than in any other cancer and it's not even close. We have more FDA-approved therapies, maybe it's 37, I think, every minute it changes. It's more FDA-approved therapies than breast cancer and this is the fifth most common cancer, lymphoma and DLBCL, the most frequent subtype, but still, not nearly as many patients as breast cancer or lung cancer, all these other things. So we're very lucky. More therapies for a small number of patients means that it's more personalized therapy, trying to get the right therapy for the right person, not just R-CHOP for everybody maybe as it used to be 10, 15 years ago. The advances are rapid and quite exciting.

Of course, we have newer immunotherapies like CAR-T cells, first approved in third line. Now for more than year ago approved in second line therapy. But even more recently some proof that one of those CAR-T cells, we have two in second line therapy, axi-cell and liso-cell. And we have more recent evidence that axi-cell, specifically in this randomized trial, ZUMA-7, demonstrated an overall survival benefit, not just a PFS benefit as we saw near the end of the trial. There's not a lot of right and wrongs or black and whites in medicine. You know, it's right to give aspirin to patients with heart attacks and maybe beta blockers. But this is getting close to be a right and wrong. If a patient's relapse early from DLBCL, meaning within a year after R-CHOP or something similar and they could tolerate a CAR-T and axi-cell therapy, it's probably your right answer. Maybe liso-cell, the TRANSFORM trial will show that same outcome with more follow-ups, we have to see. But that's a big advance.

Third and second line CAR-T for DLBCL. We have many newer types of CAR-Ts being studied, attacking CD19s, CD20, CD22. There's so many trials of these, we can't go through 'em all, but all kind of promising. And then the other big advance, again, immunotherapy, is the development of bispecific antibodies and this has been rapid development. CAR-T, you know, have been studied in lymphoma for well more than a decade and slowly working their way from third line to second line. Bispecific antibodies only FDA-approved a few months ago for third line DLBCL and also for follicular a few months before that.

And already being studied in second line therapy, first line therapy, first line in combination with other medicines, first line as monotherapy. So this is unprecedented rapidity of patients getting access in different contexts. We have a few FDA-approved ones now, epcoritamab, glofitamab for DLBCL, mosunetuzumab for follicular lymphoma, and others being studied. Odronextamab in lots of trials for DLBCL and others. But the big advance is how we are studying them in every possible setting, not just DLBCL, but mantle cell lymphoma, follicular lymphoma, other subtypes, especially some profoundly unmet needs like Richter syndrome where the advances have been very slow. So rapid progress, moving them to more spaces, into earlier lines of therapy, in different combinations, with chemo, with Revlimid, with BTK inhibitors, many, many permutations of how we can make these be better. And in those combinations we already have some results.

I mean, just the simplest stuff of chemo plus bispecifics, awesomely effective in early trials, you know, 30, 50 patient trials but you know, response rates of 90% for example, with the gem plus OX plus epcoritamab and complete remissions in, you know, the majority of patients and many of these patients were refractory to prior chemo, so you know, had very poor prognosis before these developments. So yeah, immunotherapies broadly and CAR-T and bispecific specifically, super exciting, and literally month by month we're getting newer and cooler trials, finding new ways to make these work better.