KEY TAKEAWAYS
- The phase 2 ELM-2 trial did a prespecified analysis of the DLBCL cohort, with ORR evaluated by ICR as a primary endpoint.
- The study confirmed that odronextamab showed clinically meaningful efficacy, durable CRs, and a manageable safety profile in pts with highly aggressive R/R DLBCL.
- The 0.7/4/20 step-up regimen also mitigated the risk of high-grade CRS, making it a good alternative for managing R/R DLBCL.
The global, multicenter study enrolled adult patients with diffuse large B-cell lymphoma (DLBCL) who were relapsed/refractory (R/R) after ≥2 prior lines of therapy (LOT), including an anti-CD20 Ab and an alkylator. CAR T therapy was not permitted earlier. IV odronextamab was administered in 21-day cycles with steroid prophylaxis and step-up dosing during Cycle (C) 1. The initial step-up regimen was 1 mg split over C1 Day (D) 1 and C1D2, and 20 mg split over C1D8 and C1D9, followed by the 160 mg full dose on C1D15 (1/20 regimen).
The regimen was adjusted to reduce the risk of cytokine release syndrome (CRS). The revised regimen involved 0.7 mg dose split over C1D1 (0.2 mg) and C1D2 (0.5 mg), 4 mg dose split over C1D8 and C1D9, and 20 mg over C1D15 and C1D16, followed by the full 160 mg dose on C2D1 (0.7/4/20 regimen). 160 mg QW continued till the end of C4, 320 mg Q2W till disease progression or unacceptable toxicity. The primary endpoint was ORR evaluated by independent central review (ICR).
There were 140 patients, with a median age of 66 years (ranging from 24 to 88) and a male majority of 59%, who were treated till 15 September 2022. Ann Arbor stage III-IV was observed in 80% pts, with a median prior LOT of 2 (ranging from 2 to 8). Primary refractory was present in 57% pts, while 66% were double refractory to anti-CD20 Ab and an alkylator in any LOT. The study followed up for 21.3 months and found high ORR and CR rates of 49% and 31%. These rates remained consistent across high-risk subgroups. The study also found durable CRs with a median duration of 17.9 months and a 48% probability of ongoing CR at 18 months.
TEAEs were reported in 99% pts, with 88% having treatment-related TEAEs. 5 pts had treatment-related Gr 5 AEs and 11 discontinued due to treatment-related AEs. Most common TEAEs observed were (55%), anemia (42%), and pyrexia (39%). Of 73 patients on the 0.7/4/20 regimen, 1 pt had Gr 3 CRS. No cases of Gr 4 or 5 CRS were reported. None required mechanical ventilation or ICU admission for CRS management. ICANS was noted in only one patient at Gr 2 severity.
Odronextamab proved to be an effective treatment for hard-to-treat R/R DLBCL patients, with lasting CRs and a manageable safety profile. The 0.7/4/20 step-up regimen reduces the risk of high-grade CRS, making it a viable option for managing R/R DLBCL.
Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_93
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03888105
Poon, M., Walewski, J., Kim, T. M., Cho, S., Jarque, I., Iskierka-Jażdżewska, E., Prince, H. M., Oh, S. Y., Lim, F., Carpio, C., Tan, T., Ayyappan, S., Gutierrez, A., Li, J., Ufkin, M., Zhu, M., Chaudhry, A., Mohamed, H., Ambati, S., Kim, W. S. ODRONEXTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): RESULTS FROM A PRESPECIFIED ANALYSIS OF THE PIVOTAL PHASE II STUDY ELM-2. Hematological Oncology, 41, 141-142. https://doi.org/10.1002/hon.3163_93
