ABSTRACT
Title
New drug for rare disease
Authors
PL. Zinzani
Abstract
Background: Hodgkin lymphoma (HL) is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells and sALCL is a CD30-expressing malignancy comprising ~2-3% of all NHL cases. The antibody-drug conjugate (ADC) brentuximab vedotin (SGN-35) delivers the highly potent antimicrotubule agent monomethyl auristatin E (MMAE) to CD30-positive malignant cells by binding specifically to CD30 on the cell surface and releasing MMAE inside the cell via lysosomal degradation. Binding of MMAE to tubulin disrupts the microtubule network within the cell, induces cell cycle arrest, and results in apoptotic death of the CD30-expressing tumor cell.
Studies Results A pivotal, phase II, single-arm, multicenter study evaluated the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory HL after autologous stem cell transplant (SCT). Pts received brentuximab vedotin 1.8 mg/kg q3 weeks as a 30‑minute outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).
102 patients were enrolled and the median age was 31 yrs (range, 15–77 yrs). Patients had received a median of 3.5 (range 1–13) prior cancer-related systemic therapies excluding autologous SCT. 71% of pts had primary refractory disease and 42% had not responded to their most recent prior therapy. The ORR per IRF assessment was 75% (76 of 102 pts), with complete remissions (CRs) in 34% of pts (n=35).
At the time of database lock (August 2010), the median duration of follow up from first dose was ~9 months (for responders). The median duration of response for pts with CR per IRF has not yet been reached (range 0.3+ to 61.4+ wks); follow up continues and 6+ months of additional data will be available for presentation.
A phase II, single-arm, multicenter study evaluated the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory sALCL. Pts received brentuximab vedotin 1.8 mg/kg q3 weeks as a 30‑minute outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to Cheson 2007.
58 patients were enrolled and median age was 52 yrs (range 14–76 yrs). 72% of pts had ALK negative sALCL. Pts had received a median of 2 (range 1–6) prior systemic therapies. 62% of them had primary refractory disease, 50% were refractory to their most recent prior therapy, and 22% had never responded to any prior therapy. At the time of primary efficacy analysis, ORR per IRF was 86% (50 of 58 pts) with CRs in 53% of pts (31 of 58).
Median duration of objective response had not yet been reached; the duration ranged from 0.3 to 45.3 wks.
Of 15 patients with malignant cutaneous lesions at baseline, 14 (93%) had resolution of all lesions; median time to resolution was 4.9 wks. After achieving a remission with brentuximab vedotin, 7 pts received an allogeneic stem cell transplant (SCT) and 7 pts had an autologous SCT.
Across both trials, brentuximab vedotin treatment was associated with generally manageable adverse events.
The most common (≥15%) treatment-related adverse events (AEs) of any grade were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. AEs ≥ Grade 3 occurring in ≥5% of pts were neutropenia, peripheral sensory neuropathy, thrombocytopenia, and anemia.
Conclusions: With manageable AEs, single-agent brentuximab vedotin induced objective responses in 75% of pts with relapsed or refractory HL. In this heavily pretreated population, 57% of patients achieved a durable CR. Brentuximab vedotin induced objective responses in 86% also of pts with highly refractory sALCL, including a high proportion of CRs, with manageable AEs.
Studies Results A pivotal, phase II, single-arm, multicenter study evaluated the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory HL after autologous stem cell transplant (SCT). Pts received brentuximab vedotin 1.8 mg/kg q3 weeks as a 30‑minute outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).
102 patients were enrolled and the median age was 31 yrs (range, 15–77 yrs). Patients had received a median of 3.5 (range 1–13) prior cancer-related systemic therapies excluding autologous SCT. 71% of pts had primary refractory disease and 42% had not responded to their most recent prior therapy. The ORR per IRF assessment was 75% (76 of 102 pts), with complete remissions (CRs) in 34% of pts (n=35).
At the time of database lock (August 2010), the median duration of follow up from first dose was ~9 months (for responders). The median duration of response for pts with CR per IRF has not yet been reached (range 0.3+ to 61.4+ wks); follow up continues and 6+ months of additional data will be available for presentation.
A phase II, single-arm, multicenter study evaluated the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory sALCL. Pts received brentuximab vedotin 1.8 mg/kg q3 weeks as a 30‑minute outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to Cheson 2007.
58 patients were enrolled and median age was 52 yrs (range 14–76 yrs). 72% of pts had ALK negative sALCL. Pts had received a median of 2 (range 1–6) prior systemic therapies. 62% of them had primary refractory disease, 50% were refractory to their most recent prior therapy, and 22% had never responded to any prior therapy. At the time of primary efficacy analysis, ORR per IRF was 86% (50 of 58 pts) with CRs in 53% of pts (31 of 58).
Median duration of objective response had not yet been reached; the duration ranged from 0.3 to 45.3 wks.
Of 15 patients with malignant cutaneous lesions at baseline, 14 (93%) had resolution of all lesions; median time to resolution was 4.9 wks. After achieving a remission with brentuximab vedotin, 7 pts received an allogeneic stem cell transplant (SCT) and 7 pts had an autologous SCT.
Across both trials, brentuximab vedotin treatment was associated with generally manageable adverse events.
The most common (≥15%) treatment-related adverse events (AEs) of any grade were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. AEs ≥ Grade 3 occurring in ≥5% of pts were neutropenia, peripheral sensory neuropathy, thrombocytopenia, and anemia.
Conclusions: With manageable AEs, single-agent brentuximab vedotin induced objective responses in 75% of pts with relapsed or refractory HL. In this heavily pretreated population, 57% of patients achieved a durable CR. Brentuximab vedotin induced objective responses in 86% also of pts with highly refractory sALCL, including a high proportion of CRs, with manageable AEs.