Promising Outcomes with Pola-R-CHP in Newly Diagnosed Diffuse Large B Cell Lymphoma with Aberrant p53 Expression

Background:

Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of aggressive lymphomas. Previous studies indicated that the prognosis of DLBCL patients with aberrant P53 expression was dismal, even though they received R-CHOP chemotherapy as the first-line regimen.

Aims:

This study aimed to evaluate the clinical efficacy and treatment tolerance of the Pola-R-CHP regimen in diffuse large B cell lymphoma (DLBCL) patients with aberrant P53 expression.

Methods:

We enrolled newly diagnosed DLBCL patients with aberrant P53 expression from our hospital in China between June 2023 and April 2024. Aberrant P53 expression was defined as greater than 50% or less than 5%. We collected clinical information, overall response rates, and adverse events for all patients. The Pola-R-CHP regimen included polatuzumab vedotin (1.8 mg/kg), rituximab (375 mg/m²), cyclophosphamide (750 mg/m²), liposomal doxorubicin (30 mg/m²) on day 1 of each cycle, and prednisone (100 mg orally, once daily on days 1 through 5 of each of the first six cycles).

Results:

Thirty newly diagnosed DLBCL patients with aberrant P53 expression were enrolled, with a median age of 66 years (range 33-79). The male-to-female ratio was 7:8. Based on the Ann Arbor staging system, 80% of patients were classified as stage III/IV, and 53.3% had an International Prognostic Index (IPI) score of ≥3. Seventy percent of patients had at least two extranodal lesions, with the spleen, gastrointestinal tract, kidneys, adrenal glands, uterus, and ovaries being the most commonly involved organs. The white blood cell count, hemoglobin, and platelet count were nearly normal across all patients. High levels of lactic dehydrogenase and β2 microglobulin were found in 60% and 56.7% of patients, respectively. According to the Hans algorithm, 73.3% of patients were in the non-GCB group, and the median Ki-67 value was 80% (range 60%-95%). Three patients were CD5 positive, and 50% were diagnosed with double- expressor lymphoma. Among the cohort, six patients had P53 protein expression less than 5%, while 24 patients exhibited expression greater than 50%. TP53 gene mutation analysis (exon 4-10) revealed that all patients with P53 expression less than 5% had TP53 mutations. Furthermore, 91.7% and 87.5% of patients with P53 expression greater than 80% and 50%, respectively, had TP53 mutations. Among these thirty patients, 86.7% of patients exhibited TP53 gene mutations, with the most common mutations occurring between exons 5 and 8. All patients completed at least three cycles of the Pola-R-CHP regimen. The overall response rate (ORR) was 96.7%, with a complete response rate (CRR) of 46.7% at the end of the third cycle. By the end of treatment, the ORR was 91.7%, and the CRR was 83.3%. The most common adverse events were hematologic toxicities, with 33.3% of patients experiencing grade 3/4 granulocytopenia after three cycles.

Conclusion: Immunohistochemical analysis indicated a high TP53 gene mutation risk in patients with P53 expression patterns of less than 5% or greater than 80%. The Pola-R-CHP regimen demonstrated high response rates and good tolerability in DLBCL patients with aberrant P53 expression, making it an effective therapeutic option.