CD19-Directed Antibody-Drug Conjugates for DLBCL
Matthew S. McKinney, MD, discusses the tolerability observed in the LOTIS-2 trial of loncastuximab tesirine of patients with relapsed/refractory diffuse large B-cell lymphoma.
Matthew S. McKinney, MD, assistant professor of medicine at Duke University School of Medicine, discusses the tolerability observed in the LOTIS-2 trial (NCT03589469) of loncastuximab tesirine (Zynlonta) of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
According to McKinney, loncastuximab was generally well tolerated in the study, with the most common grade 3 or higher treatment-emergent adverse events (AEs) being cytopenias including neutropenia in 26% of patients and thrombocytopenia in 18% of patients, which he says is expected with treatment for this population. The next highest grade 3 or higher treatment-emergent AE was increased gamma-glutamyltransferase (GGT) in 17%, which was a common reason for treatment discontinuation in the study, though it is not commonly monitored in patients with DLBCL. However, McKinney says it did not appear to be dangerous to patients.
Other notable AEs included volume overload such as edema and serous infusion, which were improved after diuresis, and skin rash related to sun exposure, which can be managed with steroid premedication. Patients need to be cautioned to report these events to their physicians.
Overall, these AEs with loncastuximab can be managed, and the study results suggest that loncastuximab has favorable efficacy and tolerability, according to McKinney.
0:08 | In terms of adverse responses, in general, loncastuximab was well tolerated. One interesting thing that read out from the study is one of the more common toxicities or reasons that the study administration was stopped in individual patients was GGT elevations. That's not something that we routinely check in the [United States] and it was not something seemingly dangerous for the patients. So for the most part in real-world use, that's not going to be an issue that limits administration of loncastuximab.
0:42 | There were important safety readouts and things around monitoring and premedication that came off of LOTIS-2. One of which was that there [were] cytopenias, which is expected in this population, even with the antibody-drug conjugate [ADC] mode of administration. Interestingly enough, there was a small number of patients that had volume overload: things like edema or serous effusions. Those generally improved with diuresis. And it was also found that the novel ADC in the setting of sun exposure could cause a particular type of skin rash, and so there's precautions around steroid [premedication] before the infusions to prevent that. Patients are cautioned to watch for volume overload and notify their physicians if they have any signs of that, or if they develop rash because there can be things like steroids that can be administered to resolve that.
1:41 | Aside from those things, loncastuximab was generally well tolerated overall. And I think paired with the ease of administration and the overall encouraging efficacy, [this] makes it another exciting compound to have an armamentarium for relapsed/refractory DLBCL.