Title:Treatment of Refractory p53 Mutation Large B-cell Lymphoma with Daratumumab and Venetoclax Followed by CAR-T Cell Therapy: Case Report and Animal Study
Volume: 20
Issue: 3
Author(s): Duanhao Gong, Jia Gu, Kuangguo Zhou and Wei Huang*
Affiliation:
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, Hubei, China
Keywords:
Large B-cell lymphoma, p53 mutation, daratumumab, venetoclax, chimeric antigen receptor, T cell therapy.
Abstract:
Background: The tumor burden before chimeric antigen receptor T (CAR-T) cell
therapy was one of the critical factors affecting the prognosis of lymphoma. It was a challenge
to effectively reduce the tumor burden of relapsed/refractory large B-cell lymphoma with p53
mutation.
Objective: Here, we have presented a case of relapsed/refractory large B-cell lymphoma with
p53 mutation being controlled by the treatment with daratumumab and venetoclax, followed by
CAR-T cell therapy.
Case Presentation: The patient was a 56-year-old female who was diagnosed with relapsed/
refractory diffuse large B cell lymphoma (DLBCL) transformed from follicular lymphoma.
The patient was treated with daratumumab, venetoclax, and GEMOX (gemcitabine and
oxaliplatin) under the guidance of high-throughput drug sensitivity analysis. We used a CD38
positive lymphoma cell line with p53 mutation to construct tumor models for validating the anti-
lymphoma effect of the combination therapy of daratumumab and venetoclax.
Results: The patient achieved a complete metabolic response after treatment with daratumumab,
venetoclax, and GEMOX. Then, she further achieved a complete molecular response after she
subsequently received CAR-T cell therapy, and she has been living without a lymphoma recurrence.
The results from the animal study showed that the combination of daratumumab and venetoclax
could significantly enhance the antitumor effect on CD38-positive lymphoma with p53
mutation.
Conclusion: The results from our successful case and animal experiments provide new avenues
for the treatment of relapsed/refractory large B-cell lymphoma with p53 mutation. Further clinical
trials are reuqired to treat CD38-positive lymphoma with the combination of daratumumab
and venetoclax.
