Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma

Abstract

We present response and survival outcomes of a pivotal phase 2 trial of the antibody-drug conjugate brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplant (N = 102) after a median observation period of approximately 3 years. Median overall survival and progression-free survival were estimated at 40.5 months and 9.3 months, respectively. Improved outcomes were observed in patients who achieved a complete remission (CR) on brentuximab vedotin, with estimated 3-year overall survival and progression-free survival rates of 73% (95% confidence interval [CI]: 57%, 88%) and 58% (95% CI: 41%, 76%), respectively, in this group (medians not reached). Of the 34 patients who obtained CR, 16 (47%) remain progression-free after a median of 53.3 months (range, 29.0 to 56.2 months) of observation; 12 patients remain progression-free without a consolidative allogeneic stem cell transplant. Younger age, good performance status, and lower disease burden at baseline were characteristic of patients who achieved a CR and were favorable prognostic factors for overall survival. These results suggest that a significant proportion of patients who respond to brentuximab vedotin can achieve prolonged disease control. The trial was registered at www.clinicaltrials.gov as #NCT00848926.

Figure 1

Patients who remain in remission per the investigator following treatment with brentuximab vedotin. Includes patients who remain in remission according to the investigator, are still on study being followed for survival, and have not started new anticancer therapy (n = 18). Patients are shaded according to their best response on treatment with brentuximab vedotin. Six patients received an allogeneic stem cell transplant shortly after completing treatment with brentuximab vedotin. The 2 patients with a PR to brentuximab vedotin achieved a CR following transplant. Subsequent to end of treatment, 1 patient (indicated by an asterisk) received continued treatment with brentuximab vedotin as part of a separate treatment extension protocol.

Figure 2

OS following treatment with brentuximab vedotin. OS was analyzed using Kaplan-Meier methodology and is shown overall (A) and by best response (B). All censored patients are indicated by dots on the Kaplan-Meier curve. Patients still on study and in remission without the start of new therapy are indicated by open dots on the Kaplan-Meier curve in panel A.

Figure 3

PFS following treatment with brentuximab vedotin. PFS was analyzed using Kaplan-Meier methodology and is shown overall (A) and by best response (B). All censored patients are indicated by dots on the Kaplan-Meier curve. Patients still on study and in remission without the start of new therapy are indicated by open dots on the Kaplan-Meier curve in panel A. One patient was not evaluable for response and is excluded from panel B.

Figure 4

PFS relative to most recent prior therapy. Includes all enrolled patients (N = 102). PFS was analyzed using Kaplan-Meier methodology and was calculated for each patient’s last systemic therapy received prior to study (gray bar) and on brentuximab vedotin (black). Triangles at the end of bars indicate censored patients. Patients are sorted left to right on the x-axis according to the duration of PFS on their last systemic therapy. Sixty-five patients (64%) had longer PFS on brentuximab vedotin than their last prior therapy.