ASH 2019 – R/R B-cell NHL: mosunetuzumab shows promise in phase 1/1b trial


  • Ben Gallarda
  • Univadis
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Takeaway

  • The bispecific antibody mosunetuzumab demonstrated favorable safety and efficacy outcomes, including complete remission (CR) in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), even those with disease progression after chimeric antigen receptor T cell (CAR-T) therapy.
  • The drug could be potentially used before or after CAR-T therapy, as it is likely to boost responses in both cases.

Why this matters

  • Mosunetuzumab targets both CD3 (on T cell surfaces) and CD20 (on B cell surfaces), engaging T cells to elicit their cytotoxicity against B cells.
  • Unlike CAR T cells, which require a complex individualized production process lasting several weeks, mosunetuzumab is an off-the-shelf product.

Study design

  • Open-label, multicenter, phase 1/1b dose escalation and expansion trial.
  • Previously treated patients with R/R B-cell NHL (n=270) received mosunetuzumab (8 cycles for those achieving CR; maximum 17 cycles for those having partial response or stable disease).
  • Funding: Genentech Inc.

Key results

  • 67% patients had aggressive lymphomas, whereas 31% had indolent disease.
  • Among patients with aggressive lymphomas, 37% had objective responses and 19% achieved CR.
  • Among patients with indolent lymphomas, 63% had objective responses and 43% achieved CR.
  • Disease-free status was sustained in 71% of aggressive lymphoma and 83% of indolent lymphoma cases at 6 months since achieving CR.
  • In the subgroup of patients previously treated with CAR-T therapy (n=30), 38.9% had objective responses and 22% achieved CR.
  • The adverse event profile of mosunetuzumab was similar to that of CAR T cells.
  • Cytokine release syndrome, mostly mild, was seen in 29% of patients and moderately severe neurological toxicity was observed in 4% of patients.

Limitations

  • Open-label design.

Expert commentary

  • The lead author, Stephen J Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia suggested that “initial use of mosunetuzumab would be in patients who have already tried CAR T cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval.”