Clinical Response and Safety for Relapsed/Refractory Diffuse Large B Cell Lymphoma Treated By Glofitamab Combined with Chemo-Free Regimens

Background:

The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) is poor. Glofitamab, a bispecific antibody that recruits T cells to tumor cells, has shown promise. Still, real-world data on its combined use with chemo-free regimens for R/R DLBCL is limited.

Aims:

This study aimed to evaluate the clinical efficacy and safety of glofitamab combined with chemo-free regimens for treating R/R DLBCL.

Methods:

We enrolled patients with R/R DLBCL who had received at least two prior lines of therapy. Patients were pretreated with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy (12 cycles). R/R double-expressor lymphoma patients received glofitamab combined with acalabrutinib (100 mg twice daily) or zanubrutinib (160 mg twice daily); R/R primary mediastinal large B-cell lymphoma patients received glofitamab combined with sintilimab (200 mg per cycle); the remaining R/R patients received glofitamab combined with polatuzumab vedotin (1.8 mg/kg) or lenalidomide (20 mg/day, days 1-14). Clinical information, overall response rates, and adverse events were collected for all patients.

Results:

Fifteen R/R DLBCL patients, with a median age of 66 years (range 29-79 years), were enrolled. The male-to-female ratio was 12:3. Based on the Ann Arbor staging system, 93.3% of patients were classified as stage III/IV, and 66.7% had an International Prognostic Index (IPI) score of ≥3. 66.7% of patients had at least two extranodal lesions. According to the Hans algorithm, 93.3% of patients were in the non-GCB group, and the median Ki-67 value was 90% (range 70%-90%). Three patients were CD5 positive, and 60.0% were diagnosed with double-expressor lymphoma. Among the cohort, three patients had P53 protein expression less than 5%, while eight patients exhibited expression greater than 50%. The median number of treatment lines was four (range 3-5). Six patients had primary refractory disease, and six experienced early relapsed. In this study, nine patients received glofitamab combined with BTK inhibitors; one received glofitamab combined with sintilimab; three received glofitamab combined with lenalidomide; and two received glofitamab combined with polatuzumab vedotin. All patients completed at least three cycles, and the overall response rate was 73.3%, with a complete response rate of 33.3% at the end of the second cycle. Adverse events were generally mild, with grade 1 or 2 cytokine release syndrome and tumor flare reaction being the most common.

Conclusion:

Glofitamab combined with chemo-free regimens demonstrated high response rates and good tolerability in R/R DLBCL patients receiving at least two-line treatments.

No relevant conflicts of interest to declare.