Comparing Results with Loncastuximab in the Clinic and Real-World Settings in DLBCL

CASE

• A 73-year-old lady offered with fever, complications, and 7-lb unintentional weight reduction​.
• Medical historical past: no household historical past of most cancers, and hyperlipidemia that was effectively managed with simvastatin.
• Bodily examination: palpable bilateral cervical lymphadenopathy​
• Laboratory outcomes: lactate dehydrogenase (LDH) s265 U/L (280 U/L higher restrict); Hemoglobin 10.8 g/dL; bilirubin 1.3 mg/dL (1.2 mg/dL higher restrict); creatinine 1.7 mg/dL (1.2 mg/dL higher restrict); all others inside regular restrict​
• Hepatitis B, C and HIV unfavourable​
• Lymph node biopsy; immunohistochemistry panel: CD 10+, CD 20+, which confirmed diffuse massive B-cell lymphoma (DLBCL).
• Fluorescence in situ hybridization: unfavourable for rearrangements of BCL6, BCL2 and C-MYC​
• Complete physique PET/CT scan confirmed diffuse adenopathy, largest node 3.9 cm.
• MRI of the mind confirmed no proof of lesions​.
• ECOG efficiency standing: 1​
• Stage III illness; Worldwide Prognostic Index (IPI) rating 2: low-intermediate danger​
• Affected person obtained 6 cycles of R-CHOP [rituximab (Rituxan),cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin)], and vincristine sulfate (Oncovin), which was effectively tolerated​.
• She had a whole response (CR) on the finish of remedy, however 1 12 months later the affected person offered with diffuse lymphadenopathy, confirmed by PET CT scan​.
• Biopsy confirmed relapse of the identical DLBCL​.
• Affected person obtained 6 cycles of polatuzumab vedotin (Polivy), bendamustine (Bendeka), and rituximab (Pola-BR).
• She had secure illness for six to eight months earlier than development​.
• Present remedy:​ loncastuximab tesirine-lpyl (Zynlonta)

Focused Oncology: What had been the efficacy long-term efficacy outcomes for the LOTIS-2 trial (NCT03589469) assessing loncastuximab on this affected person inhabitants?

EMILY AYERS, MD: The general response charge [ORR] was 48.3%, with a whole response [CR] charge of 24.8%.^1,2 The event-free survival [EFS] charge at 1-year was 44.0%, after which 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 length of response [(DOR) for all treated patients] was 13.37 months [95% CI, 6.87-not reached].² Once you have a look at these sufferers who acquire a CR [with loncastuximab] the median DOR will not be reached, however these sufferers who acquire a CR with this remedy appear to nonetheless have a sturdy response. Then, as seen with different therapies, for the sufferers who obtain a partial response most of them appear to relapse early with a median DOR of solely 5.7 months [95% CI, 1.64-9.26].²

For these sufferers 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 total survival [OS], the median was not reached in these sufferers with a CR and the median OS of 9.5 months [95% CI, 6.74-11.47] was for all sufferers handled [with loncastuximab].²

Had been there any toxicities of concern with this remedy?

[The majority] of sufferers had an hostile occasion [AE] of some kind, however one thing that lots of people discuss with loncastuximab is the elevated [rate of] GGT [(gamma-glutamyl transferase) seen in 42% of patients at any grade].²

That is adopted solely primarily based on the payload with this drug, and the priority for hepatotoxicity, however often sufferers simply see an remoted GGT enhance with none decreased hepatic operate, so the medical that means of that is unclear. We even have some cytopenias [with the use of loncastuximab], after which a novel AE seen in 20% [of patients at] any grade is peripheral edema and fluid accumulation.² [However], there have been no new security alerts that had been recognized within the long-term follow-up.

How does loncastuximab within the real-world setting evaluate with the outcomes within the medical setting?

There was a real-world evaluation from 21 completely different websites [in the United States]…that included 187 sufferers with a median age of 68 years [95% CI, 22-95].³ In contrast with the LOTIS-2 research, virtually 20% of those sufferers had double-hit DLBCL, and nearly all of sufferers had prior chimeric antigen receptor [CAR] T-cell remedy at 60%, however the real-world outcomes didn’t maintain as much as what we noticed on LOTIS-2.3 There was a CR charge of 14% and an ORR of 33% with a median PFS and OS of two.1 months and 4.6 months, respectively. This evaluation did present that these sufferers with non-bulky [disease] and people sufferers who had a CR to the latest remedy previous to loncastuximab nonetheless had considerably improved outcomes.³

Did prior CAR T-cell remedy influence these outcomes? How did these sufferers with a CR to loncastuximab fare total?

Apparently, prior CAR T-cell remedy didn’t influence outcomes [in the real-world setting].³ So, these sufferers who had prior CAR T-cell remedy did the identical as these sufferers with out prior CAR T-cell remedy. PFS by the response to loncastuximab, as you’d anticipate, these sufferers with a CR do higher. However the median PFS was not reached for these sufferers reaching a CR, so despite the fact that the CR charges are low with this drug, these sufferers who can obtain a CR appear to have sturdy responses. On the flip facet of that, these sufferers who progress [do so] early and have very poor outcomes.³

^References

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

^{2. Caimi PF, Ai WZ, Alderuccio JP, et al. Loncastuximab tesirine in relapsed/refractory diffuse massive B-cell lymphoma: long-term efficacy and security from the section 2 LOTIS-2 research. Haematologica. doi:10.3324/haematol.2023.283459}

^{3. Ayers E, Zelikson V, Gurumurthi A, et al. Loncastuximab in high-risk and heavily-pretreated relapsed/refractory diffuse massive B-cell lymphoma: An actual world evaluation from 21 US facilities. Blood. 2023;142(Suppl 1):312. doi:10.1182/blood-2023-174257}