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ASH 2021: Blinatumomab for Patients with Richter’s Syndrome: A Multicenter Phase 2 Trial from the Filo Group

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This research was presented by Dr. Romain Guieze and colleagues at the American Society for Hematology annual meeting which was held December 2021 (ASH 2021).

Background:

Richter’s syndrome is a rare complication of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) where the cancer cells transform into a much more aggressive lymphoma. It is associated with very rapid disease progression, limited therapeutic options, and poor survival, because the lymphoma does not respond well to traditional treatments. While chemotherapy is often used to treat Richter’s syndrome, it is not very effective. It has been suggested that modulating anti-tumor immunity might be a promising approach in treating Richter’s syndrome.

Bispecific antibodies are a new experimental class of immunotherapy drugs which work by bringing your immune cells in close proximity to chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) cells. The bispecific antibody blinatumomab transiently links CD3-positive T cells to CD19-positive B-cells, inducing T-cell activation and subsequent destruction of tumor cells.

Takeaways:

  • This study is a phase 2 multicenter study investigating the efficacy and safety of blinatumomab after chemotherapy (R-CHOP) debulking therapy for patients with untreated Richter’s syndrome.
  • The patients with persisting or progressive disease after 2 cycles of R-CHOP were eligible to receive an 8-week course of blinatumomab.
  • Thirty-four patients have enrolled in the trial thus far, and 18 have completed blinatumomab treatment.
  • Ten patients did not receive blinatumomab. Seven patients achieved complete remission with R-CHOP, 2 patients died prior to receiving blinatumomab, and 1 patient developed severe pneumonia prior to receiving blinatumomab.
  • Of the 18 patients who completed blinatumomab treatment, all experienced at least one side effect (adverse event).
  • Observed adverse events included fever (4 patients), cytokine release syndrome (2 patients), sepsis (2 patients), blood clot in a deep vein (2 patients), low red blood cell count (4 patients), low white blood cell count (3 patients), low lymphocyte count (5 patients), low blood platelet count (3 patients) and high blood sugar levels (5 patients).
  • Five patients (28%) experienced neurotoxicity, and all recovered.
  • Blinatumomab was temporarily stopped in 3 patients and permanently stopped in 2 patients.
  • Of the 18 patients who completed blinatumomab treatment, 4 (22%) patients achieved complete remission, 4 (22%) patients were in partial remission, 2 (11%) patients were stable, and the remaining 8 (45%) had progressive disease.
  • When the whole treatment strategy was considered (R-CHOP debulking followed by blinatumomab), the overall response rate was 54%, and 39% of patients achieved complete remission.

Conclusions:

Richter’s syndrome is difficult to treat, and treatment options are pretty limited. In this study, about 20% of patients achieved complete remission with chemoimmunotherapy alone, which is similar to the rates seen in other studies. Blinatumomab treatment was helpful for some patients, but not everyone benefited and there were some serious side effects. As always, it’s important to talk with your doctor about the potential risks and benefits of new therapies.

Here is the link to the ASH 2021 abstract for more details.

Take care of yourself first.

Ann Liu, PhD