Effectiveness of BTK Inhibitors in MYD88^mut/CD79B^mut DLBCL

MCD (MYD88^L265P/CD79B^mut) diffuse large B-cell lymphoma (DLBCL) presents with a dismal prognosis, lacking established treatment protocols.

Ting Deng and the team suggest no published clinical research findings concerning zanubrutinib or orelabrutinib as initial therapies for MCD DLBCL.

Researchers performed an inclusive analysis of 23 newly diagnosed DLBCL patients with MYD88^mut and/or CD79B^mut from June 2020 to June 2022 who received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab + lenalidomide (R²). A control group of 17 patients with MYD88^mut and/or CD79B^mut DLBCL who received the standard R-CHOP therapy was also assessed. Clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate, and progression-free survival (PFS) of the two groups were retrospectively analyzed.

About the main clinical features, a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40, 67.5%) were noted. Among the 23 DLBCL patients, 18 received BTKi + R-CHOP, and five elderly DLBCL patients were treated with BTKi + R². Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1-year PFS rate 41.2%), improved ORR, CRR, and PFS results were observed in the BTKi + R-CHOP group (100%, 94.4%, and 88.9%, P= 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression, or IPI score, patients in the BTKi + R-CHOP group had better PFS than patients in the control group.

In the BTKi + R-CHOP group, no significant difference was found in ORR, CRR, and PFS based on subtype analysis, while BTKi-type subgroups exhibited statistically significant differences in 1-year PFS (P = 0.028). There were no significant differences in grade 3-4 hematological toxicity (P= 1) and grade 3-4 non-hematological toxicity (P= 0.49) between the BTKi + R-CHOP and R-CHOP treatment groups. In the BTKi + R² group, the ORR was 100%, the CRR was 80%, and the 1-year PFS rate was 80%. The incidences of grade 3-4 hematologic toxicity and non-hematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients.

The study concluded that newly diagnosed DLBCL patients with MYD88^mut and/or CD79B^mut may benefit from BTKis according to real-world clinical data.

This study was supported by the National Natural Science Foundation of China

Source: https://pubmed.ncbi.nlm.nih.gov/38457222/

Deng T, Zhang S, Xiao M, et al.(2024). “A single-centre, real-world study of BTK inhibitors for the initial treatment of MYD88^mut /CD79B^mut diffuse large B-cell lymphoma.” Cancer Med. 2024 Feb;13(4):e7005. doi: 10.1002/cam4.7005. PMID: 38457222; PMCID: PMC10923040.