Contributions
Abstract: PB1785
Type: Publication Only
Session title: Stem cell transplantation - Clinical
Background
Mutations in the TP53 gene in lymphoid malignancies occur in about 19,3% of cases. Patients are carrying mutations in TP53 do not benefit from intensive chemotherapy regimen and have poor prognosis. The only approach to achieve long-term remission is to use cell therapy in the first line: allogeneic hematopoietic cell transplantation and CAR-T cell therapy. The use of targeted therapy does not allow achieving long-term remissions and is justified only as a bridge to cell therapy.
Aims
To evaluate the prognostic value of mutations in the TP53 gene in patients with B-cell lymphoid malignancies and the results of therapy in this group of patients.
Methods
During the period from 2016 to 2021, 95 patients with B-cell lymphoid malignancies were included in the prospective study: 47 pts - mantle cell lymphoma, 16 pts - primary mediastinal lymphoma, 12 pts - diffuse large B-cell lymphoma, 8 pts - 'double-hit' lymphoma, 7 pts - follicular lymphoma grade 3, 3 pts - Burkitt's lymphoma, 1 pt – plasmablastic lymphoma, 1 pt - chronic lymphocytic leukemia. Sanger DNA sequencing and NGS carried out analysis of mutations in the TP53 gene.
Results
TP53 mutations were detected in 18 of 95 patients (19%): 11 pts – mantle cell lymphoma, 2 - diffuse large B-cell lymphoma, 1 pt - 'double-hit' lymphoma, 1 pt - Burkitt's lymphoma, 1 pt - primary mediastinal lymphoma and 1 pt – plasmablastic lymphoma. In our study of eight patients with mutations in the TP53 gene underwent haploidentical (4), matched unrelated (3), mismatched related (1) allo-HCT between 2016 and 2021.
Five out of 8 patients before allo-HCT received targeted therapy: 4 patients as a bridge to allo-HCT after previous chemotherapy (3 pt - MCL, 1 pt – DLBCL), 1 pt with PL - in combination with induction chemotherapy (mNHL-BFM-90 + lenalidomide) and 1 patient with CLL - in as a first-line therapy ibrutinib with venetoclax was administered before allo-HCT.
Five out of 8 patients remain in complete remission of the disease without signs of GVHD with follow-up from 1 to 52 months: 3 pt – mantle cell lymphoma, 1 pt - plasmablastic lymphoma, 1 pt - chronic lymphocytic leukemia.
Three out of 8 patients died after allo-HCT: 1 pt - due to severe toxic and infectious complications (DLBCL), 2 pt – due to progression disease (MCL).
One patient with «double-hit» lymphoma underwent CAR-T cell therapy. With a follow-up period of 6 months, the patient remain in complete remission.
Among other patients five died of disease progression (4 pts – MCL, 1 pt – BL, 1 pt – PML), despite the use of various chemotherapy regimens and targeted therapy. Four patients are currently undergoing therapy.
Conclusion
The presence of mutations in the TP53 gene is characterized by an extremely unfavorable impact on the prognosis and survival of patient with lymphoid malignancies. TP53 mutations should be considered for risk models in all B-cell lymphoid malignancies. Allo-HCT improves outcomes for patients with mutant TP53. CAR-T cell therapy can serve as an alternative approach to the therapy of patients with B-cell lymphoid malignancies with mutations in the TP53 gene.
Keyword(s): Allogeneic hematopoietic stem cell transplant, CAR-T, Chronic lymphocytic leukemia, Lymphoma
Abstract: PB1785
Type: Publication Only
Session title: Stem cell transplantation - Clinical
Background
Mutations in the TP53 gene in lymphoid malignancies occur in about 19,3% of cases. Patients are carrying mutations in TP53 do not benefit from intensive chemotherapy regimen and have poor prognosis. The only approach to achieve long-term remission is to use cell therapy in the first line: allogeneic hematopoietic cell transplantation and CAR-T cell therapy. The use of targeted therapy does not allow achieving long-term remissions and is justified only as a bridge to cell therapy.
Aims
To evaluate the prognostic value of mutations in the TP53 gene in patients with B-cell lymphoid malignancies and the results of therapy in this group of patients.
Methods
During the period from 2016 to 2021, 95 patients with B-cell lymphoid malignancies were included in the prospective study: 47 pts - mantle cell lymphoma, 16 pts - primary mediastinal lymphoma, 12 pts - diffuse large B-cell lymphoma, 8 pts - 'double-hit' lymphoma, 7 pts - follicular lymphoma grade 3, 3 pts - Burkitt's lymphoma, 1 pt – plasmablastic lymphoma, 1 pt - chronic lymphocytic leukemia. Sanger DNA sequencing and NGS carried out analysis of mutations in the TP53 gene.
Results
TP53 mutations were detected in 18 of 95 patients (19%): 11 pts – mantle cell lymphoma, 2 - diffuse large B-cell lymphoma, 1 pt - 'double-hit' lymphoma, 1 pt - Burkitt's lymphoma, 1 pt - primary mediastinal lymphoma and 1 pt – plasmablastic lymphoma. In our study of eight patients with mutations in the TP53 gene underwent haploidentical (4), matched unrelated (3), mismatched related (1) allo-HCT between 2016 and 2021.
Five out of 8 patients before allo-HCT received targeted therapy: 4 patients as a bridge to allo-HCT after previous chemotherapy (3 pt - MCL, 1 pt – DLBCL), 1 pt with PL - in combination with induction chemotherapy (mNHL-BFM-90 + lenalidomide) and 1 patient with CLL - in as a first-line therapy ibrutinib with venetoclax was administered before allo-HCT.
Five out of 8 patients remain in complete remission of the disease without signs of GVHD with follow-up from 1 to 52 months: 3 pt – mantle cell lymphoma, 1 pt - plasmablastic lymphoma, 1 pt - chronic lymphocytic leukemia.
Three out of 8 patients died after allo-HCT: 1 pt - due to severe toxic and infectious complications (DLBCL), 2 pt – due to progression disease (MCL).
One patient with «double-hit» lymphoma underwent CAR-T cell therapy. With a follow-up period of 6 months, the patient remain in complete remission.
Among other patients five died of disease progression (4 pts – MCL, 1 pt – BL, 1 pt – PML), despite the use of various chemotherapy regimens and targeted therapy. Four patients are currently undergoing therapy.
Conclusion
The presence of mutations in the TP53 gene is characterized by an extremely unfavorable impact on the prognosis and survival of patient with lymphoid malignancies. TP53 mutations should be considered for risk models in all B-cell lymphoid malignancies. Allo-HCT improves outcomes for patients with mutant TP53. CAR-T cell therapy can serve as an alternative approach to the therapy of patients with B-cell lymphoid malignancies with mutations in the TP53 gene.
Keyword(s): Allogeneic hematopoietic stem cell transplant, CAR-T, Chronic lymphocytic leukemia, Lymphoma