Evaluating the Role of Loncastuximab in Relapsed/Refractory DLBCL

Brad Haverkos, MD, MPH, MS

Associate Professor, Medicine-Hematology

University of Colorado School of Medicine

Aurora, CO

DISCUSSION QUESTIONS

• How has the approval of loncastuximab tesirine (Zynlonta) addressed an unmet need in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL)? ​
• In which patient population is loncastuximab most suitable for? ​
  • Are there any instances in which you choose not to use loncastuximab?​
• How do you plan to use loncastuximab in the context of other available therapies?​

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BRAD HAVERKOS, MD: Does the approval of loncastuximab address an unmet need in the treatment of patients with relapsed/refractory DLBCL? What do you all think about that question?

XIANTUO WU, MD: In the LOTIS-2 trial [NCT03589469], the patient population has at least failed 2 lines of previous treatment.¹ Some patients received chimeric antigen receptor [CAR] T-cell therapy or autologous transplant. These are difficult patients, pretty heavily treated and also given a single agent. The data are amazing. I haven’t used it but the data—there’s no question about it—this data is very solid. The adverse event profile is also acceptable, and probably manageable, too. Certainly, if I have the proper patient, I will seriously consider this agent.

HAVERKOS: Those are all good points. The patient population is relapsed, pretty heavily pretreated, pretty high risk, both patients that had prior autologous stem cell transplant and some allogeneic stem cell transplant on this trial, and prior CAR T-cell therapy patients as well, at around 10%. I appreciate your comments there. Do others have thoughts about loncastuximab based on the data or their experience?

HOLAVANAHALLI KESHAVAPRASAD, MD: I think after 2 prior lines of therapy, especially in the high-risk patients, loncastuximab definitely seems to have a role. Now, the only thing is, what’s your overall recommendation regarding tafasitamab [Monjuvi] and lenalidomide [Revlimid], especially if patients are not candidates for CAR T-cell therapy or transplant? Because the results I’ve seen are pretty good and it’s fairly well tolerated and long disease-free survival data when patients respond to treatment.² That’s something I thought was appropriate in some patients. What do you think?

HAVERKOS: Those are good points. I think it will be interesting to draw contrast to the patients that were on the LOTIS-2 trial versus those that kind of went on the tafasitamab/lenalidomide, [since it is] important to think about maybe some of those differences.

KESHAVAPRASAD: The complete response [CR] rate was a bit higher with tafasitamab, but, of course, they were not these high-risk patients.^1,2

HAVERKOS: Yes, exactly. Are there other comments or thoughts on loncastuximab?

SANTHOSH AMBIKA, MD: I don’t know, I still feel like a time-limited [therapy like] glofitamab-gxbm [Columvi] may be my choice before loncastuximab.

HAVERKOS: Yes, [we have a] blessing of riches [in treatment options].

WU: I’m curious about [something] because this patient population was pretty heavily treated with all these [prior therapies]. Is there any correlations between CD19 expression at all versus efficacy?

HAVERKOS: In the trial, there were 10% of patients who received prior CD19-targeted CAR T-cell therapy.¹ They’ve looked at, in other subsequent studies, if CD19 [expression] is necessary for patients to respond. It seems that you can be CD19-negative and still respond to this drug. But to me, it’s a question of what assay you’re using to measure CD19 and there are different sensitivities of different assays. It’s a question of how much CD19 you need to have on the cell for a patient to respond. The drug is targeting CD19, so I think [the patient] probably needs to have a certain amount of CD19 but whether that could still be CD19-negative by immunohistochemistry, they could still respond. Maybe they have some minimal expression that you’re not picking it up by the immunohistochemical stain. I think you could still have a “CD19-negative” patient who could respond to it, but I think to Dr Ambika’s point earlier, maybe we’re at a point now where we have other drugs that are targeting other antigens. Maybe if you have a CD19-negative patient, at least my thought sometimes is that if I have a CD19-negative patient but I have epcoritamab [Epkinly] at my disposal targeting CD20, I’m probably going to choose that over loncastuximab [for them]. But I think it’s a fair discussion to have and debate.

BENJAMIN SCHEIER, MD: You could ask your breast cancer [specialist] colleagues about the HER2-low [setting] and the antibody-drug conjugates there because it’s probably a similar story. I don’t know whether they’ll see a similar thing in lymphoma or not.

HAVERKOS: Yes, it’s definitely a good point, [we can] draw a lot of parallels in other settings as well. I think we’ve all given plenty of patients rituximab [Rituxan] and you can see CD20-negative large-cell lymphoma after enough or CD20-negative B-cell lymphoma after enough rituximab, but, we keep giving it in many settings. I think we don’t know.

_REFERENCES:

_{1. Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800. doi:10.1016/S1470-2045(21)00139-X}

_{2. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978-988. doi:10.1016/S1470-2045(20)30225-4}