Clinical Response and Peripheral Blood Stem Cell Mobilization with MINE±Obinutuzumab Regimen in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of malignant tumors. Although the R-CHOP regimen significantly improves the prognosis for patients with DLBCL, 40% of cases experience relapse or become refractory. The MINE regimen (Ifosfamide, Mitoxantrone Hydrochloride Liposome, and Etoposide), with or without obinutuzumab, is a viable second-line chemotherapy option for relapsed or refractory DLBCL. However, there is currently limited research on clinical response and peripheral blood stem cell mobilization related to treating relapsed/refractory DLBCL (R/R DLBCL) with this regimen. Aims: This study evaluated the clinical response and peripheral blood stem cell mobilization associated with treating R/R DLBCL using the MINE regimen with or without Obinutuzumab as the second-line chemotherapy. Methods: We enrolled first-time R/R DLBCL patients from our hospital in China from January 2023 to April 2024. We collected clinical information, overall response rates, and adverse events for all patients. The MINE±obinutuzumab regimen included obinutuzumab (1000 mg), Mitoxantrone Hydrochloride Liposome (20 mg/m²) on day 1 of each cycle, and Ifosfamide (1.33 mg/m²) and Etoposide (65 mg/m²) once daily on days 1 through 3 of each of the first four cycles. Results: Twenty-one patients with first-time R/R DLBCL were enrolled, with a median age of 53 years (range 25-65). The male-to-female ratio was 11:10. Based on the Ann Arbor staging system, 81.0% of patients were classified as stage III/IV, and 71.4% had an International Prognostic Index (IPI) score of ≥3. Additionally, 66.7% of patients had at least one extranodal lesion. Elevated levels of lactic dehydrogenase and β2 microglobulin were found in 76.2% and 85.7% of patients, respectively. According to the Hans algorithm, 81.0% of patients were in the non-GCB group, and the median Ki-67 value was 80% (range 50%-90%). Only one patient was CD5 positive, and 57.1% of patients were diagnosed with double-expression lymphoma. Among the cohort, 71.4% of patients exhibited P53 protein expression greater than 50%. Ten cases were primary refractory diseases, and eight patients had early recurrence disease (relapse within one year). All patients completed at least two cycles of the MINE±obinutuzumab regimen. The overall response rate (ORR) was 95.2%, with a complete response rate (CRR) of 38.1% at the end of the second cycle. By the end of treatment, the ORR was 85.7%, and the CRR was 64.5%. After 2 cycles of this regimen, 80.0% of patients successfully collected peripheral blood stem cells, but after four cycles, only 16.7% of patients were successful. The most common adverse events were hematologic toxicities, with 76.2% of patients experiencing grade 3/4 granulocytopenia after two cycles. Conclusion: The MINE±obinutuzumab regimen demonstrated good response rates and acceptable safety in treating first-time R/R DLBCL patients. For those requiring autologous stem cell transplantation, it is recommended to collect peripheral blood stem cells as soon as possible after two cycles.