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

Treatment with naratuximab emtansine + rituximab for patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and other B-cell non-Hodgkin’s lymphomas (B-NHL) demonstrated high efficacy and a tolerable and manageable safety profile in a phase 2 study. This treatment regimen could offer a new treatment option for these patients, including heavily pre-treated patients.

Patients with r/r B-NHL and particularly r/r DLBCL who are not candidates for stem cell transplantation or CAR T-cell therapy have a poor prognosis. A surface antigen of B lymphocytes, CD37, is highly expressed in NHL and thus a potential target for therapies. Naratuximab emtansine is an antibody-drug conjugate consisting of the humanised anti-CD37 antibody K7153A that targets CD37. A phase 1 monotherapy study demonstrated a good safety profile with a 22% objective response rate (ORR) in patients with DLBCL (NCT01534715) [1].

Dr Moshe Yair Levy (Texas Oncology-Baylor Charles A. Sammons Cancer Center, TX, USA) presented a subsequent, open-label, phase 2 study (NCT02564744) of naratuximab emtansine + rituximab in r/r NHL and r/r DLBCL patients [2]. Part 1 consisted of a safety run-in (r/r NHL including DLBCL; n=17) and a run-in expansion (cohort 1, r/r DLBCL n=8 ; cohort 2, other r/r NHL n=12). Part 2 only included DLBCL patients in 2 cohorts with different treatments: cohort A (n=33) received the same treatment as all patients in part 1, consisting of 0.7 mg/kg naratuximab emtansine on day 1, followed by 375 mg/m² rituximab every 3 weeks. Cohort B (n=30) received 0.4 mg/kg naratuximab emtansine on days 1, 8, and 15, followed by 375 mg/m² on day 1. A large proportion of patients were heavily pre-treated, with advanced DLBCL. Primary endpoints were ORR and safety.

Efficacy outcomes in all treated DLBCL patients (n=80, with n=76 evaluable) showed an ORR of 44.7% with 31.6% complete response (CR). ORR in part 2 was 50% in cohorts A and B; CR was 43.3% in cohort A and 33.3% in cohort B. In patients with non-bulky DLBCL (n=61), ORR was 50.8%; in non-primary refractory, third-line+ treated patients (n=28), ORR was 46.4% and CR was 32.1%. After a median follow-up of 15 months, median duration of response was not reached; 66% of responders had a duration of response >12 months.

The most frequently observed grade 3–4 adverse events were haematological and manageable. Only 8 patients discontinued treatment due to adverse events. Of the 10 patients with grade 5 adverse events, 2 were considered treatment-related.

In summary, naratuximab emtansine + rituximab was tolerable and demonstrated high efficacy in this phase 2 study. This treatment regimen might offer a new treatment option for patients with r/r DLBCL, including heavily pre-treated patients.

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   1. Stathis A, et al. Invest New Drugs 2018;36(5):869-76.
   2. Levy MY, 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 Virtual Congress, 9–17 June.

 

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Posted on 5 August 202115 February 2024