Promising data from Debiopharm International’s CD37-targeting antibody drug conjugate naratuximab emtansine (formerly Debio 1562) in combination with Roche’s Rituxan (rituximab) was presented at this year’s virtual European Haematology Association meeting (EHA 2021), held on 9–17 June. The data suggest this therapy is safe and can elicit good, durable responses in patients with relapsed or refractory B-cell lymphomas.
The majority (80%) of patients enrolled in the study had relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) and were split across two dosing cohorts. Cohort A was dosed every three weeks, while cohort B was dosed weekly. Part I of the study also included patients with a range of B-cell malignancies, including follicular lymphoma, mantle cell lymphoma and marginal zone lymphoma.
The overall response rate (ORR) for all evaluable patients was 44.7%, with a complete response (CR) rate of 31.6%. There was little difference seen between the dosing cohorts in R/R DLBCL patients, with an ORR of 50% in each, and CR rates of 43.3% in cohort A and 33.3% in cohort B. Responses from both DLBCL cohorts also appeared to be durable, with a median duration of response not yet reached at 15 months follow-up.
There is no uniform standard of care for R/R DLBCL. Despite this, the multi-cohort retrospective SCHOLAR-1 study, which assessed the outcomes of refractory DLBCL patients, reported a median overall survival of just 6.3 months for first-line refractory patients, so the naratuximab emtansine data seems encouraging. Naratuximab emtansine was also relatively well-tolerated, with just eight patients discontinuing treatment due to adverse events.
These results are impressive given the trial’s inclusion criteria. Patients with Eastern Cooperative Oncology Group (ECOG) performance statuses of between zero and two, and who had received between one and six prior lines of therapy, were included in the trial. Out of the DLBCL patients, 44% had received at least two prior lines of therapy.
Patients with double or triple hit lymphomas, ‘bulky disease’ or transformations were also included in the trial. Patients with these tumour characteristics typically have more aggressive diseases and poorer prognoses, and are often excluded from trials. The safety data presented at EHA emphasises the relative frailty of these patients, as ten patients receiving treatment experienced a Grade Five adverse event leading to death, although just two of these were attributed to the study treatment.
Despite a flurry of approvals for novel agents for the treatment of DLBCL in recent years, patients who relapse within two years still have a very poor prognosis. GlobalData believes naratuximab emtansine could be an effective therapeutic option in this difficult-to-treat patient group, and could be particularly beneficial in older or frail patients with progressive disease for which stem cell transplants or CAR-T therapies are not an option.