R/R DLBCL: Treating With Tafasitamab-Lenalidomide

Ian W. Flinn, MD, PhD: Amit, have you started using this regimen, tafasitamab, lenalidomide, in your practice? Maybe I’ll get a few opinions on this, actually. What patient population are you using the regimen in? What are your thoughts?

Amitkumar Mehta, MD: This is a very effective regimen, especially for those patients who are not eligible for transplant, as approved based on the L-MIND study. As I was mentioning, in the frontline setting for frail, older patients who are not candidates for aggressive therapy, and similarly in the relapsed setting, those patients are perfect for this combination.

And as Dr Kami Maddocks mentioned, the key with this combination is management of lenalidomide adverse effects. If you manage those, you will be able to successfully implement and get a successful outcome in your patients who are frail. I’ve been using this regimen. As I mentioned, the dose and management of lenalidomide’s adverse effects is key in these patients.

Ian W. Flinn, MD, PhD: John, I want to get your opinion on this. I’ve also heard Loretta speak eloquently on this in the past. In regard to sequencing, should we just be using this regimen in older and infirm patients? Some people worry about using a CD19 antibody in patients for whom you’re considering trying to get them to CAR [chimeric antigen receptor] T cells. There are a lot of theoretical reasons, probably less data. Maybe you could walk us through how you’re using this regimen in your practice. Is it similar to Amit, or are you doing things differently?

John M. Burke, MD: I’ve used it only once in an older patient who was frail. Her prior therapies included R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], or mini-CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], and then POLA-BR [polatuzumab vedotin, bendamustine, rituximab]. She had been through both of those regimens and then had another relapse. It came down to, “Well, she’s not an autologous transplant candidate.” We also decided she was probably not a CAR T candidate for various reasons. So we had excluded using curative therapies, as Loretta had alluded to before. You know, “Is this someone we’re going to really try to cure?” We felt she was too frail because of her comorbidities.

That’s an example of where I’ve used it. In this particular case, it didn’t go well. She was probably even too frail for tafasitamab and lenalidomide. She got pretty weak and was tired after just a couple of weeks, and wound up having various unrelated medical complications. But that’s an example of how I would attempt to use it. It’s approved for second-line therapy, but it’s not something you want to use in someone who’s going to go through an autotransplant. 

Is there value in using this regimen prior to CAR T? Is there harm in using this regimen prior to CAR T? Is the anti-CD19 antibody removing CD19? Do you lose CD19 expression, thereby rendering a subsequent CAR T product less effective?

We don’t have great data on that. There are some in vitro data out of the Mayo Clinic suggesting that probably does not happen. There are also a couple of case reports of patients who have been successfully treated with 1 CD19 product followed by another. The best we can tell is it doesn’t seem to be a problem, but I’m not a CAR T-cell doctor. I actually don’t know what they think about this. I suspect they have some theoretical concerns, as you alluded to.

Loretta J. Nastoupil, MD: Obviously we have a lot of enthusiasm surrounding the potential cure with CAR T, recognizing it’s a small portion. It’s probably about 40% of patients. There is concern that if you’re introducing a CD19-directed therapy based on what we’ve observed in ALL [acute lymphoblastic leukemia], maybe you’re going to select out for CD19-negative clones.

However, that is not supported by any evidence. It’s theoretical, and we’ve looked at outcomes among patients who received CD19-directed standard-of-care CAR T. It didn’t matter what their CD19 expression level was prior to receipt of that therapy, whether it was determined by IHC [immunohistochemistry] or flow and not even known. But that was also in patients for whom the vast majority had never seen a CD19-directed therapy.

What we really need is more real-world experience, where people have seen these agents and they have been sequenced in various ways. I suspect we’ll have tafasitamab prior to CD19-directed CAR T-cell therapy, and vice versa. 

As John mentioned, in the small amount of data that currently exist, it does not appear that introducing tafasitamab prior to CD19-directed CAR T-cell therapy is going to impact that legacy.

Transcript Edited for Clarity

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