Treatment of Refractory p53 Mutation Large B-cell Lymphoma with Daratumumab and Venetoclax Followed by CAR-T Cell Therapy: Case Report and Animal Study

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: 19

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

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.

Cite this article as:

Gong Duanhao, Gu Jia, Zhou Kuangguo and Huang Wei*, Treatment of Refractory p53 Mutation Large B-cell Lymphoma with Daratumumab and Venetoclax Followed by CAR-T Cell Therapy: Case Report and Animal Study, Recent Patents on Anti-Cancer Drug Discovery 2024; 19 () . https://dx.doi.org/10.2174/0115748928273058231128073414