Our clinical trial of glofitamab and RICE investigated the addition of the bispecific antibody glofitamab, which targets CD20 and CD3 and which is a new immunotherapy, in addition with a standard salvage chemotherapy called RICE which is rituximab and three different chemotherapy regimens. It was aimed at investigating the use of this regimen in second-line therapy for patients with diffuse large B-cell lymphoma who are potentially eligible to undergo an autologous transplant or a CAR T-cell therapy. The standard therapy for salvage of patients who are going to a stem cell transplant with the addition of a bispecific antibody which is a new immunotherapy.
What was the study design?
This was a phase Ib clinical trial evaluating the addition of the two drugs. It included 43 patients, patients were treated with obinutuzumab first day as well as they started ICE chemotherapy on the first day, they received it for the first three days of treatment and then they started a dose ramp-up on cycle 1 day 8 of glofitamab then on day 15 with glofitamab and then subsequently started on a second cycle with ICE and rituximab, receiving glofitamab on day 8 of each cycle. They received up to three cycles of treatment and after completing the three cycles patients in complete remission could go to an autologous transplant or CAR T-cell therapy. This is a single-arm non-randomised study.
What are the key results?
The study enrolled 43 patients, the evaluable patients were 42. The patients were relatively high-risk patients who were older than 65 years of age. 30% of the patients were primary refractory, 30% of the patients had relapse within 12 months of initial treatment and 72% had relapsed later than 72 months. The majority of patients had diffuse large B-cell lymphoma but also a percentage of patients, about 12%, had double hit lymphoma. The overall response rate, which is the primary endpoint, was 83% with 66.7% of patients achieving a complete response which is a very active regimen for relapsed diffuse large B, in comparison with standard chemoimmunotherapy. The rates of response were comparable among disease groups, particular risk disease groups, including patients who had early or late relapse, with all patients having responses in the 75-80% rate for overall response rate.
In terms of safety, the rates of high grade cytokine release syndrome, which is a complication that is frequently seen with patients receiving bispecific antibodies, was very low. No patients had grade 3/4 cytokine release syndrome. We did see haematologic toxicity with about 50% of patients having thrombocytopenia and a similar number of patients having grade 3/4 anaemia as well as about 30% of patients having grade 3/4 neutropenia.
There were no grade 5 fatal events and the rate of discontinuation secondary to adverse events was very low. The rate of cytokine release syndrome, again, was very low with only grade 1 and 2 events and most of them were on cycle day 1 and day 8. There were a couple of infections but those were in two patients so that accounted for about 4.8% serious infections.
The fixed duration treatment of 2-3 cycles of treatment with glofitamab and rituximab and ICE chemotherapy with a very high response rate and very high complete response rate with a relatively manageable adverse event profile.
What is the significance of these results?
The study is very significant in the sense that most of the chemotherapy that we have used for salvage or second line therapy for diffuse large B-cell lymphoma has not been very active over the last decade to two decades, with response rates that achieve 40% remission in the best case scenario, usually it’s a little bit lower. The addition of glofitamab to this standard chemoimmunotherapy achieved very high response rates and allowed patients to proceed to salvage treatments with autologous consolidation or CAR T-cells. The fact that it was well tolerated suggests that the rate of toxicity, or the additional toxicity, from the addition of the bispecific is low which is encouraging. It really helps to suggest that we can achieve better disease control before we consolidate with an autologous transplant. So it’s certainly an improvement on what we’ve had before.
