Insights Into Immunotherapies For Adults With TP53-Mutated Acute Lymphoblastic Leukemia

In a Pharmacy Times^® interview Jose Tinajero, PharmD, BCOP, a clinical pharmacist specialist at the City of Hope National Medical Center in Los Angeles, California, discusses findings from a study, presented at the 2024 European Hematology Association Congress, evaluating the efficacy of chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

TP53 is one of the most common mutations in cancer and has been described in a variety of cancer types. Image Credit: © Zhanna - stock.adobe.com

Pharmacy Times: Can you discuss the finding of the previous study as they evaluate TP53 mutations and inferior outcomes of CAR T-cell therapy and how did this inform the study design?

Jose Tinajero, PharmD, BCOP: TP53 is one of the most common mutations in cancer and has been described in a variety of cancer types. Previously, there have been studies looking at the impact of TP53 mutations in [ALL] and have linked it to chemotherapy refractoriness and decreased overall survival. One of the previous studies from Zeng et al showed that one of the factors associated with a lower complete remission rate in CD19 CAR [chimeric antigen receptor] T-cell therapy was the presence of TP53 mutation. So, this really inspired us in given the landscape that ALL is evolving with the introduction of novel therapies earlier into ALL treatment paradigm. This inspired us to conduct a retrospective study to evaluate this phenomenon, and so that we presented our findings at EHA [2024 European Hematology Association Congress] this year.

Pharmacy Times: What novel agents in your abstract study did you evaluate in your cohort of TP53 mutated patients?

Tinajero: Some of these novel agents we evaluated were blinatumomab [Blincyto; Amgen, Inc], which is a CD19 bispecific T-cell engager inotuzumab [Besponsa; Pfizer], which is a CD22 antibody drug conjugate and CD19 CAR T-cell therapy.

Pharmacy Times: Regarding the study population, what kind of patients had these mutations. Any noticeable differences amongst the novel agents such as CAR T?

Tinajero: We identified 43 adult patients with B-cell ALL with TP53. They received a total of 73 individual novel treatments. All patients were treated with blinatumomab in our cohort, approximately half the patients were treated with inotuzumab, and 16.3% of the patients were treated with CAR T-cell therapy. As far as some of the description are mean age, the time of first novel therapy was 52 years of age, and the majority of patients were male and Hispanic. As far as some other descriptions, CAR T-cell therapy was administered after more prior lines compared to blinatumomab and inotuzumab, and more frequently had higher rates of prior allogeneic stem cell transplant.

Pharmacy Times: Regarding the correlation between TP53 mutations and CAR T-cell therapy outcomes, what were the results in this patient population?

Tinajero: As far as some of that response rate, the CR [complete remission], Cri [complete remission with incomplete hematologic recovery] rate was 62.5% 68.2 and 71.4% after blinatumomab and CAR T-cell therapy, respectively. With the corresponding MRD [minimal residual disease] negativity rates of 96% 57.1% and 80% among these responders, 16.3% 17.4 and 28.5% of the patients receiving blinatumomab and have CAR T-cell therapy underwent consolidation with allogeneic stem cell transplant.

Pharmacy Times: What approaches could be used with novel and/orCAR T therapy resistance as it relates to TP53 mutations?

Tinajero: We described that the activity amongst novel and CAR T-cell therapy remains encouraging. Currently, an ongoing analysis is comparing patients who receive consolidation with allogeneic stem cell transplant compared to those who did not. We plan to also perform a leukemia free and overall survival analysis. In addition, we aim to perform additional analysis to look at other co variables associated with response and leukemia free survival.