Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Combination therapy, Therapies
Aims: To investigate the efficacy of Zanubrutinib combined with immunochemotherapy in pts with CD79A/CD79B-mutant DLBCL. The primary objective is complete response rate (CRR).
Methods: Pts aged 18-80 years with CD79A/CD79B-mutant DLBCL and adequate organ function are being enrolled. This study consisted of treatment naïve (TN) cohort and relapsed/refractory (R/R) cohort. Zanubrutinib (160 mg po bid) plus R-CHOP (ZR-CHOP) was administered in TN cohort, and Zanubrutinib (160 mg po bid) combined with investigator-determined conventional salvage chemotherapy (CSC, including ICE, DHAP, GDP, or GemOx, +/- rituximab) was administered in R/R cohort. A totally of 7 cycles of treatment was planned for TN patients. After 5 cycles of induction treatment, responders in R/R cohort undergo autologous stem cell transplantation (ASCT) or Zanubrutinib maintenance for 12 months, based on the patient’s fitness and preference.
Results: From July 2020 to 22 July 2022, 137 pts have been screened, including 103 TN pts and 34 R/R pts. CD79A/CD79B mutation was identified in 26 (25.2%) TN pts and in 14 (41.2%) R/R pts, of which 14 TN pts and 10 R/R pts agreed to participate in this trial. Their baseline characteristics are displayed in Table 1.
By 30 July 2022, 12 TN pts and 9 R/R pts had been evaluated for response. There were 10 CRs (83.3%) and 2 PRs (16.7%) in the TN cohort; 5 CRs (55.6%), 2 PRs (22.2%), and 2 PDs (22.2%) in the R/R cohort. The median follow-up time was 6.4 (2.6 – 24.5) months for the TN cohort and 11.8 (1.4 – 14.9) months for the R/R cohort. One pt (5TN) died from non-tumor-related disease and no PD was observed in the TN cohort. In the R/R cohort, 3 pts experienced PD (all harbored TP53 mutations) and 2 of them (4R/R and 10R/R) died, another pt (8R/R) died from non-tumor-related disease.
The most common adverse events in both cohorts were hematologic toxicities. Grade 3/4 AEs occurred in ≥20% pts were neutropenia, leukopenia, anemia, thrombocytopenia, and infection. Bleeding and cardiac events were not observed.
Conclusion: CD79A/CD79B mutation was frequent in DLBCL patients, especially in R/R cases. Zanubrutinib combined with immunochemotherapy showed encouraging activity and acceptable tolerance in pts with CD79A/CD79B-mutant DLBCL. TP53 mutation seemed to be a detrimental factor. The study is still ongoing and it is worth looking forward to updating the long-term survival data.
Disclosures: No relevant conflicts of interest to declare.
OffLabel Disclosure: Zanubrutinib, a BTK inhibitor, was used in combination with immunochemotherapy in the first-line treatment of DLBCL.
See more of: Oral and Poster Abstracts