During a Case-Based Roundtable® event, Emily Ayers, MD, discussed the long-term results with loncastuximab in patients with diffuse large B-cell lymphoma and how this drug fared in the real-world setting in the second article of a 2-part series.
CASE
Targeted Oncology: What were the efficacy long-term efficacy results for the LOTIS-2 trial (NCT03589469) assessing loncastuximab in this patient population?
EMILY AYERS, MD: The overall response rate [ORR] was 48.3%, with a complete response [CR] rate of 24.8%.1,2 The event-free survival [EFS] rate at 1-year was 44.0%, and then EFS at 2 years was 31.0%, and the median time to response was 42.0 days or 2 cycles [of treatment].2
The median duration of response [(DOR) for all treated patients] was 13.37 months [95% CI, 6.87-not reached].2 When you look at those patients who obtain a CR [with loncastuximab] the median DOR is not reached, but those patients who obtain a CR with this therapy seem to still have a durable response. Then, as seen with other therapies, for the patients who achieve a partial response most of them seem to relapse early with a median DOR of only 5.7 months [95% CI, 1.64-9.26].2
For those patients with a CR...the median progression-free survival [PFS] was not reached...and the median PFS for all comers was 4.9 months [95% CI, 2.89-8.31].2 Looking at overall survival [OS], the median was not reached in those patients with a CR and the median OS of 9.5 months [95% CI, 6.74-11.47] was for all patients treated [with loncastuximab].2
Were there any toxicities of concern with this therapy?
[The majority] of patients had an adverse event [AE] of some sort, but something that a lot of people talk about with loncastuximab is the increased [rate of] GGT [(gamma-glutamyl transferase) seen in 42% of patients at any grade].2
This is followed solely based on the payload with this drug, and the concern for hepatotoxicity, but usually patients just see an isolated GGT increase without any decreased hepatic function, so the clinical meaning of this is unclear. We also have some cytopenias [with the use of loncastuximab], and then a unique AE seen in 20% [of patients at] any grade is peripheral edema and fluid accumulation.2 [However], there were no new safety signals that were identified in the long-term follow-up.
How does loncastuximab in the real-world setting compare with the outcomes in the clinical setting?
There was a real-world analysis from 21 different sites [in the United States]...that included 187 patients with a median age of 68 years [95% CI, 22-95].3 Compared with the LOTIS-2 study, almost 20% of these patients had double-hit DLBCL, and the majority of patients had prior chimeric antigen receptor [CAR] T-cell therapy at 60%, but the real-world outcomes did not hold up to what we saw on LOTIS-2.3 There was a CR rate of 14% and an ORR of 33% with a median PFS and OS of 2.1 months and 4.6 months, respectively. This analysis did show that those patients with non-bulky [disease] and those patients who had a CR to the most recent therapy prior to loncastuximab still had significantly improved outcomes.3
Did prior CAR T-cell therapy impact these outcomes? How did those patients with a CR to loncastuximab fare overall?
Interestingly, prior CAR T-cell therapy did not impact outcomes [in the real-world setting].3 So, those patients who had prior CAR T-cell therapy did the same as those patients without prior CAR T-cell therapy. Looking at PFS by the response to loncastuximab, as you would expect, those patients with a CR do better. But the median PFS was not reached for those patients achieving a CR, so even though the CR rates are low with this drug, those patients who can achieve a CR seem to have durable responses. On the flip side of that, those patients who progress [do so] early and have very poor outcomes.3
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