Naratuximab emtansine plus rituximab is safe and effective in diffuse large B-cell lymphoma

The safety and efficacy of naratuximab emtansine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma and other B-cell non-Hodgkin lymphomas were evaluated in a phase 2 study. Results demonstrated high efficacy and a tolerable and manageable safety profile. This treatment regimen could represent a new treatment option for these patients, including heavily pre-treated patients.

Patients with refractory or relapsing (r/r) B-cell non-Hodgkin lymphoma (B-NHL) and particularly r/r diffuse large B-cell lymphoma (DLBCL) who do not qualify as candidates for a stem-cell transplant or CAR-T cell therapy have a poor prognosis. Naratuximab emtansine is a humanised antibody-drug conjugate targeting CD37, a surface marker of B-lymphocytes. A good safety profile with a 22% overall response rate (ORR) was demonstrated previously in a phase 1 monotherapy study in patients with DLBCL (NCT01534715) [1].

Dr Moshe Yair Levy (Texas Oncology-Baylor Charles A. Sammons Cancer Center, TX, US) presented a subsequent, open-label, phase 2 study (NCT02564744) for naratuximab emtansine plus rituximab in r/r B-NHL and r/r DLBCL patients, consisting of 2 parts [2]. Part 1 consisted of a safety run-in and a run-in expansion. Participants were divided into cohorts: cohort 1 consisted of r/r DLBCL, and cohort 2 consisted of other r/r B-NHLs. All participants in part 1 received 0.7 mg/kg naratuximab emtansine plus 375 mg/m² rituximab intravenously every 3 weeks. Part 2 included only DLBCL patients in 2 cohorts with different treatments: cohort A received the same treatment as all patients in part 1. Cohort B received naratuximab emtansine on days 1 (0.4 mg/kg), 8 (0.2 mg/kg), and 15 (0.2 mg/kg), combined with 375 mg/m² rituximab on day 1. This cycle was repeated 6 times with possible extension. Patients were followed up for 1 year after the last patient first dose. The primary endpoints were treatment-emergent adverse events (AEs) and ORR. Efficacy was only assessed in patients with DLBCL.

Included in this study were 100 participants, of which 80 had DLBCL and 20 had other B-NHLs. A large proportion of patients were heavily pre-treated and had advanced DLBCL. Treatment-emergent AEs of grade 3 or higher were observed in 81 patients (81%). The most frequently observed grade 3–4 AEs were haematological and manageable; only 8 patients discontinued treatment due to treatment-related AEs. Of the 10 patients with grade 5 AEs, 2 were considered treatment-related.

Efficacy outcomes in all 80 treated DLBCL patients demonstrated an ORR of 44.7% and 31.6% complete responses (CR). In patients with non-bulky DLBCL, ORR was 50.8%; in non-primary refractory patients that were treated at least third-line, ORR was 46.4% and CR was 32.1%. ORR was 50% in each cohort, with a CR rate of 43.3% in cohort A and 33.3% in cohort B. After a median follow-up of 15 months, the median duration of response was not reached; 66% of responders had a duration of response >12 months.

In summary, the safety profile of naratuximab emtansine plus rituximab was tolerable and manageable, while demonstrating high efficacy. This treatment regimen could represent a new treatment option for patients with r/r DLBCL, including heavily pre-treated patients.

1. Stathis A et al. Invest New Drugs 2018;36(5):869-76.
2. Yair Levy M, et al. Safety and efficacy of CD37-targeting naratuximab emtansine plus rituximab in diffuse large B-cell lymphoma and other non-Hodgkin’s B-cell lymphomas – a phase 2 study. P205-3, EHA 2021 Congress, 09–17 June.

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Posted on 16 June 20215 August 2021