Glofitamab Shows Efficacy in BTK Inhibitor-Refractory MCL

Tycel Phillips, MD, discusses the potential use of glofitamab as therapy for patients with relapsed/refractory mantle cell lymphoma.

Tycel Phillips, MD, a clinical associate professor of hematology and medical oncology at the University of Michigan, discusses the potential use of glofitamab as therapy for patients with relapsed/refractory mantle cell lymphoma (MCL).

Glofitamab is a bispecific antibody that binds to CD20 and CD3. According to Phillips, glofitamab showed high efficacy in a phase 1/2 trial (NCT03075696) that included patients who were previously treated with Bruton’s tyrosine kinase (BTK) inhibitors and those who were not. Patients received obinutuzumab (Gazyva) followed by fixed or step-up doses of glofitamab. Those who had prior BTK inhibitor therapy had an overall response rate (ORR) of 82.4%, while those who had no previous BTK inhibitor had an ORR of 75%.

In terms of adverse events (AEs), all reported cytokine release syndrome (CRS) events were manageable, and there was a single grade 1 neurotoxicity: an immune effector cell-associated neurotoxicity syndrome (ICANS)-like AE. Overall, glofitamab demonstrated a favorable safety profile.

Patients with MCL who do not respond to BTK inhibitors have limited options besides chimeric antigen receptor (CAR) T-cell therapy, which is only available in a small number of treatment centers and not all patients are eligible. If it continues to demonstrate efficacy and tolerability, glofitamab will offer an alternative for patients with advanced MCL that could be given in all treatment centers and private practices.

TRANSCRIPTION:

0:08 | So, what we were able to establish and demonstrate in this study is a very high efficacy in those patients who were naive to BTK inhibitors and those who were actually exposed and refractory to BTK inhibitors.

So, it proves that this agent could potentially be another option for those who failed BTK inhibitors. As of right now the only effective agent we typically have that we can offer these patients is utilization of the CAR T [cell] treatment, which has its own limitations based on non-select sites that can do [CAR T-cell therapy] and also some of the complications that may prevent some of the older patients being eligible. So, I think one of the key points in addition to the efficacy is the safety of this treatment. We have very low incidence of CRS. We only reported 1 episode of neurotoxicity, which was also a grade 1 neurotoxicity; it resolved very quickly in this treatment modality.

So, in that regard, based on the off-the-shelf applicability of this agent and the ability as of right now to be to be very safe, this is something that potentially could be used in a wider array of treatment facilities, not necessarily select academic centers that are accredited to give CAR T. So in some situations, you can see this given in some private practice facilities, that they've become more accustomed with this agent, which, in essence will allow more patients to be treated with these treatments, compared to what we can sort of see right now with some of these more limited treatments such as CAR T.