Different Options Discussed for DLBCL in Later-Lines of Treatment

Matthew Ulrickson, MD (Moderator)

Chief, Section of Hematology

Banner MD Anderson Cancer Center

Gilbert, AZ

DISCUSSION QUESTIONS

• Have you utilized tafasitamab (Monjuvi) plus lenalidomide (Lenvima) for patients with diffuse large B-cell lymphoma (DLBCL) since its FDA approval?
  • What has been your experience and your patients’ experience with this combination?
  • Which patients are most appropriate to receive tafasitamab/lenalidomide?
• For a patient that needs disease control quickly, is your treatment approach different?
  • What patient factors most influence your decision?

MATTHEW ULRICKSON, MD: Importantly, with somebody's disease that's growing quickly—and I even think that bispecific therapies should be here—does that change your thoughts on what you will pick? And if so, why and how?

CHRISTOPHER CHEN, MD, MBA: If it's super quick, sometimes you have to treat inpatient, so the treatment options are then much more limited than on the outpatient side. So that's super quick, then I'm going to end up giving a dose of gemcitabine/oxaliplatin or something inpatient, whereas outpatient, I think you have maybe some time to play with treatment options.

ULRICKSON: That's a great point, because you have to live with the practicalities. We would like to have bispecifics [such as] tafasitamab or whatever it is in the in the hospital, but we don't have access. How about people's thoughts on bispecifics and timeliness to response? What's been the experience in terms of speed to response on bispecifics?

BRAD HAVERKOS, MD: Certainly, the time to response with bispecifics has been pretty quick for me. That's the experience in the trials as well. I have heard from other people that they've seen some progressions in the ramp-up period with bispecifics. There's been some concern that maybe that's because of the ramp up and the lower doses, but it's not what I've observed. The people that don't respond are just people that don't respond, regardless of what dose you're giving them. I'm not sure if that's a real concern, or just something that we're attributing to the dose ramp up, but I've seen very quick responses, even with the low dose and the ramp up; impressive in patients with very bulky disease. So, it's been a remarkable therapy for some patients.

DISCUSSION QUESTIONS

• Now that there are several novel agents available in the relapsed/refractory setting for DLBCL, what is the optimal treatment selection and sequencing strategy for patients in the third line setting?
  • Does your sequencing strategy change if you need to bridge to CAR T-cell therapy?

HAVERKOS: [When talking about] epcoritamab [Epkinly] and glofitamab [Columvi], I heard epcoritamab targets a different portion of the epitope of CD20. Do you think about that in clinical practice? It's hard to choose between those 2.

ULRICKSON: I can tell you about a patient who is on my mind who had, for their follicular lymphoma, received bendamustine/rituximab [Rituxan; BR] and had bronchiolitis obliterans with a FEV1 that got down to 20%. He was CD20 positive, and he did have good response to BR for a number of years but progressed. It was the early days of CAR [chimeric antigen receptor] T-cell therapy and small bulk of disease. He got CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] in the past as a second-line therapy, and then in the third line he got CAR T. We gave a dose of [tisagenlecleucel (Kymriah)], he got through that well. Now 3 years later, he has relapsed. The biopsy is of a skin nodule.

So, I can't say entirely if its follicular or large cell lymphoma, but in somebody with that significant reaction to rituximab, I can tell you I'm not thrilled to engage the exact spot again, not knowing why it happens. So that is what pushed me in the other direction. Whereas for other patients, I like the ability to give the obinutuzumab [Gazyva] first, try to decrease disease a little bit, give glofitamab. I also do like the concept of a fixed-duration therapy as opposed to ongoing. But if somebody gets out a year and a half on a bispecific, it's not at the top of my list of things I'm worried about because I'm just thrilled that they're responding.

Any thoughts on what you give if you're thinking somebody's heading to CAR T-cell therapy vs not?

ROBERT D. YOO, DO: If a patient is heading to CAR T-cell therapy, I would probably save loncastuximab [Zynlonta] and use just polatuzumab without bendamustine. So, I would generally use CD19-specific therapy including loncastuximab and tafasitamab.

ULRICKSON: Certainly, there is mechanism resistance, about a third lose that CD19 as a relapse after CAR T-cell therapy. How many that are not CAR centers are giving bispecifics. I always love hearing about this and hearing about that. How did you build that program? What did it look like to do without CAR T-cell therapy coming first?

YOO: I work at St. Joseph's Hospital; I'm talking with the pharmacy leaders who have been on board but I don't think having a drug in is a problem. I don't think convincing the hospital is a problem because I'll probably tell them, I'll give the patient 1 dose in the hospital. But the thing is the management of cytokine release syndrome [CRS] and educating the emergency department and internal medicine staff. So, I'm working with the pharmacy to come up with the protocols.

ULRICKSON: That's great. I would love to find a forum, not only in Arizona, but everywhere. It's a similar challenge of how do you expand therapy? There are low incidence of significant CRS but important so we can keep treating more patients.