Brentuximab Vedotin for ALK+ Large B-cell Lymphoma
Brentuximab vedotin is FDA-approved and recommended for relapsed/refractory Large B-cell Lymphoma (LBCL) when used in combination with lenalidomide and rituximab, but this indication is not specific to ALK+ status—it applies to DLBCL NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma after two or more lines of systemic therapy in patients ineligible for auto-HSCT or CAR T-cell therapy. 1
Understanding the FDA Indication
The FDA approved brentuximab vedotin specifically for relapsed or refractory LBCL (including DLBCL NOS, DLBCL arising from indolent lymphoma, or HGBL) in combination with lenalidomide and a rituximab product after two or more lines of systemic therapy. 1
This approval does not distinguish between ALK+ and ALK- status in Large B-cell Lymphoma—the indication is based on CD30 expression and disease characteristics, not ALK status. 1
The recommended dosage for LBCL is 1.2 mg/kg up to a maximum of 120 mg every 3 weeks in combination with lenalidomide and rituximab until disease progression or unacceptable toxicity. 1
Critical Distinction: ALK+ ALCL vs. ALK+ LBCL
The evidence base for brentuximab vedotin is overwhelmingly in ALK+ Anaplastic Large Cell Lymphoma (ALCL), not ALK+ Large B-cell Lymphoma:
In ALK+ ALCL, brentuximab vedotin demonstrates exceptional efficacy with an overall response rate of 81% (69% complete response) and estimated 5-year OS and PFS rates of 56% and 37%, respectively. 2
The FDA approved brentuximab vedotin for systemic ALCL (both ALK+ and ALK-) after failure of at least one prior multiagent chemotherapy regimen based on these robust data. 2
For pediatric ALK+ ALCL specifically, brentuximab vedotin combined with chemotherapy showed a 2-year event-free survival of 79.1% and overall survival of 97.0% in newly diagnosed patients. 3
Clinical Application for ALK+ LBCL
If your patient has ALK+ Large B-cell Lymphoma (not ALCL) that is relapsed/refractory:
Confirm CD30 expression on the tumor cells, as brentuximab vedotin targets CD30, not ALK. 1
Verify the patient has received at least two prior lines of systemic therapy and is not eligible for auto-HSCT or CAR T-cell therapy. 1
Use brentuximab vedotin at 1.2 mg/kg (maximum 120 mg) every 3 weeks in combination with lenalidomide and rituximab. 1
Starting with cycle 2, rituximab intravenous treatment can be substituted with rituximab and hyaluronidase human via subcutaneous injection every 3 weeks. 1
Important Caveats
ALK positivity alone does not predict brentuximab vedotin response—the drug targets CD30, not ALK. The strong evidence for ALK+ disease exists only in the context of ALCL (a T-cell lymphoma), not B-cell lymphomas. 2, 1
Monitor for peripheral neuropathy (most common adverse event, occurring in 57% of ALCL patients), though it typically resolves or improves after treatment completion. 2
Be vigilant for progressive multifocal leukoencephalopathy (PML)—JC virus infection resulting in PML and death can occur with brentuximab vedotin. 1
Avoid use in patients with severe renal impairment (CrCL <30 mL/min). 1