Complete Remissions with Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma Shustov AR et al.

Proc ASH 2010;Abstract 961.

Background

   Systemic anaplastic large cell lymphoma (sALCL) is a CD30-positive aggressive subtype of peripheral T-cell lymphoma (PTCL).

– Comprises approximately 2-3% of all cases of non-Hodgkin’s lymphoma Patients with newly diagnosed high-risk ALK-positive and ALK negative sALCL have a poor prognosis. – Approximately 50% will fail front-line therapy – Few salvage therapies exist for relapsed or refractory sALCL – Pralatrexate is the only FDA-approved treatment for recurrent PTCL (including sALCL) Brentuximab vedotin (SGN-35) is a novel antibody-drug conjugate.

– Delivers the highly potent antimicrotubule agent monomethyl auristatin E (MMAE) to CD30-positive malignant cells Shustov AR et al. Proc ASH 2010;Abstract 961.

Study Schema

Accrual = 58 (Closed)

Eligibility

Relapsed or refractory sALCL Measurable disease ≥1.5 cm FDG-avid ECOG PS 0-1 Brentuximab vedotin, 1.8 mg/kg IV q 3-weeks x (up to) 16 cycles

Primary Endpoint:

Overall objective response rate (ORR) by independent review facility (IRF)

Secondary Endpoints:

Complete remission rate Duration of response Progression-free survival (PFS) Overall survival (OS) Safety and tolerability Shustov AR et al. Proc ASH 2010;Abstract 961; ClinicalTrials.Gov Identifier NCT00866047.

Efficacy Outcomes (n = 58)

Response

Overall response rate Complete remission Partial remission Stable disease Progressive disease

Secondary Endpoints

Median duration of OR Median duration of CR Median PFS Median OS

IRF

86% 53% 33% 3% 5%

Investigator

81% 59% 22% 9% 3%

IRF

Not reached Not reached Not reached

Investigator

36 weeks Not reached 41 weeks Not reached Shustov AR et al. Proc ASH 2010;Abstract 961.

Maximum Tumor Reduction per IRF

100 50 0 -50 97% of patients achieved tumor reduction -100

Individual Patients (n = 57)*

* 57 of 58 patients with post-baseline CT assessments With permission from Shustov AR et al. Proc ASH 2010;Abstract 961.

Select Adverse Events

Treatment-Related Adverse Events (AE)

Nausea Peripheral sensory neuropathy Fatigue Pyrexia Diarrhea Rash Neutropenia Thrombocytopenia Anemia

All Grades*

38% 38% 34% 33% 29% 21% 21% Not reported Not reported

Grade 3 or 4*

Not reported 10% 3% † Not reported Not reported Not reported 21% 14% 7% † † *All grade AEs occurring in ≥20% of patients and Grade 3/4 AEs occurring in ≥5% of patients Grade 3 only Shustov AR et al. Proc ASH 2010;Abstract 961.

Author Conclusions

    Remission was achieved by 86% of highly refractory systemic ALCL patients.

– Complete remission rate: 53% (by IRF) – Patients achieving tumor reduction = 97% Complete remissions observed in ≥50% of patients with ALK-negative and ALK-positive disease.

Brentuximab vedotin treatment is associated with a manageable adverse event profile.

Brentuximab vedotin is a promising new agent in the management of systemic ALCL.

Shustov AR et al. Proc ASH 2010;Abstract 961.

Investigator comment on brentuximab vedotin (SGN-35) in relapsed or refractory systemic anaplastic large cell lymphoma (sALCL)

sALCL is one of the subtypes of peripheral T-cell lymphoma (PTCL) and constitutes about 20 percent of PTCLs. This trial essentially shows that in the relapsed/refractory setting, brentuximab as a single agent has good activity with a high response rate. A total of 58 patients received treatment, which does not appear to be a huge number, but for a subset of PTCL, it is a big number. Activity of other single agents in relapsed T-cell lymphomas is in the range of 20 to 30 percent, so the response rates reported here are very promising in this specific subset of T-cell lymphoma. The drug might become available within the next year for relapsed disease, and ultimately people will consider incorporating brentuximab into earlier lines of therapy. Overall, I believe it is positive and optimistic.

Interview with Steven M Horwitz, MD, December 29, 2010