During a Case-Based Roundtable® event, Christopher Maisel, MD, discussed the data behind loncastuximab and whether participants with use this treatment for patients with diffuse large B-cell lymphoma in the first article of a 2-part series.
CASE SUMMARY
DISCUSSION QUESTIONS
Christopher Maisel, MD: Loncastuximab is an antibody-drug conjugate [ADC]…. It was studied in the phase 2 LOTIS-2 study [NCT03589469]. This is a study of relapsed/refractory DLBCL in the third line and beyond. The patients did not have to have a tumor biopsy showing CD19 expression, except if they had prior anti-CD19 therapy, such as a CD19-targeting CAR T-cell therapy.1
Loncastuximab does have the big advantage of being a strictly outpatient infusion. It is a 30-minute infusion every 3 weeks for up to a year. The first 2 doses are a loading dose, and then the other 15 cycles are at a dose which is half that; it was 0.075 mg/kg. So it is a year of therapy and then they stop. It is a fixed duration of intravenous therapy, but a 30-minute infusion each only with a little bit of dexamethasone as premedication. It was relatively easy to give in an outpatient setting. This was studied with overall response rate being the primary end point.
The median age was in the mid to late 60s. All different subtypes of lymphoma were represented, but DLBCL not otherwise specified was the most common subtype. Some of the patients had double- and triple-hit lymphoma. There were a number of patients who had had prior CAR T-cell therapy. Three prior lines of therapy was the median for the LOTIS-2 trial. Overall response rate was 48%, complete response [CR] rate was about 25%, event-free survival for at least a year was 44%, and event-free survival at more than 2 years was 31% with median time to response of less than 45 days. It was basically less than two 3-week cycles, so responses were rapid, and about half the patients responded to loncastuximab.
Progression-free survival [PFS] decreased over time, but for the patients getting a CR, the PFS data looked very impressive. And the same [is true] with overall survival; patients who got a CR were likely to remain surviving many months after treatment with loncastuximab. Clearly there's a difference between patients who get a CR and all patients in the in the study. I think we would expect that in any sort of oncologic study.
DISCUSSION QUESTIONS
Considering the LOTIS-2 data and this patient with relapsed/refractory DLBCL:
Maisel: Do you feel like loncastuximab addresses an unmet treatment need?
Nithya Palanisamy, MD: Yes, I think the data sound very good in terms of efficacy and the response, as well as being easy to [administer]. The schedule is very easy [as is the management of] the adverse events, and the data included older patients, so I don't see any downside. The data were impressive.
Henry Q. Xiong, MD, PhD: I agree the data are quite impressive. Nowadays, the treatment options for hematological malignancies are so complex, so usually after second line we decide [whether] we send patients to academic center? I think we can this treatment option handle in the community setting, so this is a good option for the patients.
Fariborz Gorouhi, MD: If we had anti-CD19 [therapy] before, we have to check the receptor?
Maisel: Yes, that was the criteria for the LOTIS-2 study.
Gorouhi: What's the cutoff, more than 0%? Is it more than 1%?
Maisel: I think it was substantial. It had to be at least 50% and the reason for this is that, particularly in patients who have had a CD19 CAR T-cell therapy, some patients relapse with a CD19 non-expressing lymphoma clone. You have a non–CD19-expressing or CD19 escape clone, and they did not want to give loncastuximab on a clinical trial to patients who had 0 expression of CD19.
Gorouhi: It's like a normal biopsy, is it biopsy or flow cytometry?
Maisel: Flow cytometry for lymphoma cells works, depending; in some cases, the cells are too large. I'd like to see both, but flow cytometry and routine immunohistochemistry are going to stain for CD19.
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