UMIN-CTR Clinical Trial

In this study, the efficacy was confirmed of retreatment with brentuximab vedotin in patients with cHL or sALCL who had achieved PR or CR with previous brentuximab vedotin therapy in Japan. AEs in patients with brentuximab vedotin retreatment did not include unexpected AEs and were generally manageable with dose modification or interruption.

The median ages of patients in safety population were 48.0 years (range, 18-86 years), including 17 males out of 28 (60.7%) and 11 females out of 28 (39.3%). The median Body Mass Index (BMI)(kg/m2)at the initiation of retreatment was 21.71 (range: 14.8-33.3). 
Eighteen out of 28 (64.3%) patients were cHL and 10 out of 28 patients were sALCL. All the patients (28;100%) were CD30 positive at diagnosis for lymphoma by immunochemistry. For anaplastic lymphoma kinase (ALK) status in sALCL patients, 3 out of 10 (30.0%) were positive and 6 out of 10 (70.0%) were negative, and 1 out of 10 was unknown. For Ann Arbor stage, 5 out of 28 (17.9%) were stage I,  5 out of 28 (17.9%) were stage II, 2 out of 28 (7.1%) were stage III and 14 out of 28 (50.0%) were stage IV, and 2 out of 28 (7.1%) were unknown. For B symptom, 18 out of 28 (34.3%) were without B symptom, 9 out of 28 (32.1%) were with B symptom, and 1 out of 28 (3.6%) was unknown. For Eastern Cooperative Oncology Group (ECOG) Performance Status, 8 out of 28 (28.6%) were stage 0, 13 out of 28 (46.4%) were 1, 4 out of 28 (14.3%) were 3 and 1 out of 28 (3.6%) were unknown.
For disease status relative to most recent prior therapy, 8 out of 28 (28.6%) were refractory and 20 out of 28 (71.4%) were relapse after response.

A total of 28 subjects (cHL; 18, sALCL; 10) were enrolled and all subjects were included in the safety population. A total of 27 subjects (cHL; 17, sALCL; 10) with exception of one patient with cHL who was not assessed for response to treatment were included in the efficacy population.

TEAEs occurred in 18 of 28 (64.3%) in all patients, 11 of 18 (61.1%) in cHL and 7 of 10 (70.0%) in sALCL. Fourteen of 28 (50.0 %) patients experienced peripheral neuropathy (sensory; n=13, 46.4%, and motor; n=3, 10.7%) were most observed TEAEs. TEAEs observed in 2 out of 28 (7.1%) were neutropenia and AST increased, respectively. TEAEs observed in 1 out of 28 (3.6%) were ALT increased, upper respiratory infection, hepatic enzyme increased and fever, respectively.
For TEAE severity, grade 2 TEAEs were most observed in 12 out of 28 patients (42.9%). Thereafter, grade 1, 3 or 4 TEAEs were observed in 6 out of 28 patients (21.4%), 4 out of 28 patients (14.3%) , and 1 out of 28 patients (3.6%). Thus, grade 1 and 2 TEAEs were most observed.
TEAEs in grade 4 were neutropenia in 1 out of 28 (3.6%). TEAEs in grade 3 were peripheral motor neuropathy in 2 out of 28 (7.1%), neutropenia and ALT increased in 1 out of 28 (3.6%), respectively. Peripheral sensory neuropathy were most observed TEAEs in grade 2 (10 out of 28 (35.7%)). Other TEAEs in grade 2 were upper respiratory infection, ALT increased and AST increased (1 out of 28 (3.6%)), respectively.  Peripheral neuropathy (sensory; n=3, 46.4%, and motor; n=1, 3.6%) were most observed TEAEs in grade 1 (4 out of 28 (14.3%)). Other TEAEs in grade 1 were fever and hepatic enzyme increased (1 out of 28 (3.6%)), respectively.Severe TEAEs were observed as peripheral motor neuropathy in 2 out of 28 patients (7.1%). TEAEs observed during brenzuximab retreatment did not include unexpected AEs.  Additionally, TEAEs were almost recovered or resolved by with dose modification or interruption (including severe TEAEs). These results suggest that AEs during brenzuximab retreatment were manageable.

The ORRs for all patients with retreatment was 59.3% (95% CI: 38.8 - 77.6).  The ORRs for patients with cHL and sALCL were 52.9% (95% CI: 27.8 - 77.0), and 70.0% (95% CI: 34.8-93.3), respectively.The median DOR for all patients, cHL and sALCL was 21.5 months (95% CI:2.6 - NA), 21.5 months (95% CI:3.2  - 21.5) and  not reached (95% CI:2.6 - NA) , respectively. The CR rate for all patients, cHL and sALCL was 33.3% (95% CI:16.5-54.0), 7.6% (95% CI:3.8 - 43.4) and 60.0% (95% CI:26.2 - 87.8), , respectively. The median PFS for all patients, cHL and sALCL was 6.1 months (95% CI:3.3- NA), 5.3 months (95% CI:2.6-24.3) and  not reached (95% CI:2.0-NA) , respectively. The median TTF for all patients, cHL and sALCL was 5.9 months (95% CI:3.3 - 12.4), 5.3 months (95% CI:2.6-12.4) and  6.1 months (95% CI:2.0-NA) , respectively.
Based on these results, the efficacy is showed in the patients with CD30 positive cHL or sALCL, who had previously achieved complete response (CR) or partial remission (PR) with prior brentuximab vedotin treatment, when who are administered brentuximab vedotin retreatment in Japan.