Fixed-duration treatment with glofitamab monotherapy has the potential to provide favourable long-term outcomes for patients with relapsed or refractory large B-cell lymphoma, a Melbourne haematologist has told delegates at Blood 2023.
Associate Professor Michael Dickinson presented extended follow-up and landmark analyses from a pivotal phase 2 study of the bispecific T-cell engager antibody, which demonstrated that most patients achieving complete response at end of treatment remained in remission.
The complete remission rate was 40% in the overall population as previously presented, with updated findings showing an estimated complete remission rate lasting 18 months of 67% with most patients experiencing no new adverse events.
A high proportion of patients with a complete response at cycle 3 (C3) remained progression free and alive at 18 months, said A/Prof Dickinson, Lead of Aggressive Lymphoma at Peter MacCallum Cancer Centre and Royal Melbourne Hospital.
This arm of the trial involved 155 patients with R/R LBCL, an ECOG performance status of 0-1 and at least two prior therapies including anti-CD20 antibody and anthracycline. Patients received obinutuzumab pretreatment seven-days prior to IV-glofitamab step-up dosing with a fixed treatment duration of 12 cycles.
Patients (median age 65) were heavily pretreated and highly refractory.
“The durable responses are really driven by complete remissions. Patients who have a partial response or progressive disease don’t benefit from glofitamab for very long,” said A/Prof Dickinson, a lead investigator on the glofitamab program.
“The PFS rate of 18 months is 72% and the overall survival rate at 18 months is 80% [at C3]. You’re looking at their response and you can tell patients in complete remission that their chances of enjoying that for 18 months are really very good.”
At end of treatment, the PFS rate at 12 months was 80% and the overall survival rate was 92%, said A/Prof Dickinson, who is also from University of Melbourne.
“The majority of patients who are in complete remission at the end of treatment were alive 12 months after end of treatment, but they are off treatment, which means that their normal B cells are recovering, their chances of toxicities from glofitamab are going down with time. This suggests that these patients may be headed towards a long-term remission and potentially cure,” he said.
Cytokine release syndrome (CRS) remained the most common adverse event, occurring in 64% of patients but events were mostly grade 1 (48%) or grade 2 (12%).
The incidence of adverse events was stable compared with earlier analyses.
There was one new grade 3 adverse event (an unexplained acute kidney injury) and two new infections (grade 4 COVID-19 and grade 2 pneumonia).
Data from earlier cohorts also confirmed the highly durable responses achieved with fixed treatment duration glofitamab. In 101 patients with R/R LBCL treated with doses of at least 10mg and below the phase 2 go-forward dose, the complete remission rate was 35% and 63% of patients were still in remission at data cutoff.
A/Prof Dickinson said on the back of the study, glofitamab was approved in the US, Canada and Europe, and funded by the NHS, with label approval in Australia.
“But we wait eagerly for someone to do something about getting it to patients.”
Glofitamab monotherapy for mantle cell lymphoma
A/Prof Dickinson also presented data from another arm of the trial showing glofitamab monotherapy with fixed treatment duration of 12 cycles induced high complete response rates in heavily pretreated patients with mantle cell lymphoma.
He said most responses were achieved early and were durable.
In this part of the trial, 37 patients in two cohorts received glofitamab step-up dosing (1g for 16 patients, 2g for 21 patients) after at least one prior therapy. Most patients had prior BTKi (64.9%) or lenalidomide (18.9%). Patients received obinutuzumab pretreatment in the week prior to their first dose of glofitamab.
After eight months, the overall response rate and complete response rate were 83.8% and 73% respectively, with a median time to complete response of 51 days.
Response at first assessment was a complete remission in about half of patients.
“Patients who were in a complete remission at the end of treatment did not relapse, there’s not a single relapse in that patient group and this certainly jives with my own clinical experience at my site,” A/Prof Dickinson told delegates.
The median estimated duration of complete response was 10 months and at the data cut-off 74.1% of patients with a complete response remained in remission.
Glofitamab was well tolerated and there were no treatment discontinuations due to adverse events. CRS events were manageable and mostly low grade.
Further, a higher dose of obinutuzumab (2g) was associated with lower any grade and grade 2 or more CRS events compared with a lower obinutuzumab dose (1g).
A/Prof Dickinson said a phase 3 study of glofitamab monotherapy against standard chemotherapies for patients who had progressed after BTK inhibitors had opened in Australia, while a study on glofitamab plus pirtobrutinib was recruiting.
The studies presented were sponsored by Roche.