Efficacy and Safety of Bendamustine, Pomalidomide, Sintilimab in Patients with Recurrent or Refractory Diffuse Large B-Cell Lymphoma: A Retrospective Study

Background:

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Approximately 40% of patients develop recurrent or refractory (R/R) diseases after frontline chemoimmunotherapy. The patients with R/R DLBCL after at least 2 lines of therapy have unsatisfactory outcome and are always encouraged to participate in clinical trials. More effective therapeutic approaches are urgently needed. Here, we conducted a study to evaluate the efficacy and safety of bendamustine in combination with pomalidomide and sintilimab for these R/R DLBCL patients.

Methods:

We retrospectively analyzed the data of R/R DLBCL patients, who had received 2-6 cycles BPD regimen: bendamustine 70mg/m², d1-2, pomalidomide (POM) 4mg, day 1-14, sintilimab, 200mg, day 2, 21 days/cycle. After 4-6 cycles therapy, patients that achieve PR or CR would continue receive pomalidomide (POM) and sintilimab as maintenance therapy for one year. The primary endpoint was objective response (ORR).

Results:

From May 2022 to July 2024, a total of 13 patients who were not eligible for transplant or CART were included. Key baseline characteristics included: Median age, 62 years (range 45-77), 76.9% IPI score 2-5, 76.9% Ann Arbor stage III-IV, 84.6% non-GCB, 46.2% dual expression, 100% EBER-negative. Patients were heavily pretreated, with a median of 3 (range 2-6) previous lines of systemic therapy. All patients were treated with RCHOP as the first line and platinum-based chemotherapy as a second line. Of these patients, 12 patients had refractory disease or early recurrence, and one experienced relapse＞12 months after the last treatment. Out of the 13 evaluable patients, the disease control rate (DCR) was 92.3%, with an overall response rate (ORR) of 11 cases (84.6%). Among them, stable disease (SD) was observed in 1/13 (7.7%) patients. Complete response (CR) was achieved in 2/13 (15.4%) cases, while partial response (PR) was seen in 9/13 (69.2%) patients. Tumor volume reduction ranged from 40% to 100%. With a median follow-up of 24 months, the median progression-free survival (PFS) was 7 months.

The most common adverse events of any grade were hemocytopenia (50.0%), infection (33.3%), digestive symptoms (16.7%). Grade 3-4 adverse events occurred in 3/13 (23.1%) patients, including neutropenia (15.4%), thrombocytopenia (15.4%), anemia (15.4%), nausea (15.4%), decreased appetite (15.4%), pneumonia (15.4%), herpes virus (7.7%). No treatment-associated death was observed.

Conclusions：

These data supported that bendamustine in combination with pomalidomide and sintilimab had promising anti-tumor activity and manageable safety profile in R/R DLBCL. Currently, a phase II, prospective study is ongoing to further investigate the efficacy and safety of this regimen (ChiCTR 2400084099).

No relevant conflicts of interest to declare.

pomalidomide was approved for relapsed/refractory multiple myeloma by FDA and NMPA, and sintilimab was approved for relapsed/refractory classical Hodgkin’s lymphoma, non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous carcinoma, Gastric and gastroesophageal junction adenocarcinoma by NMPA. Previous study showed promising efficacy of both pomalidomide and sintilimab in R/R DLBCL. We retrospectively analyzed the data of bendamustine, pomalidomide combined with sintilimab in treating R/R DLBCL patients.