What immunotherapy starting with the letter B can be used to treat T cell conditions, such as Hodgkin lymphoma or cutaneous T-cell lymphoma?

Brentuximab Vedotin for T-Cell Lymphomas

Brentuximab vedotin is the immunotherapy starting with "B" used to treat T-cell conditions including CD30+ cutaneous T-cell lymphomas, anaplastic large cell lymphoma (ALCL), and Hodgkin lymphoma. 1

Mechanism and Target

Brentuximab vedotin (BV) is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody linked to monomethyl auristatin E, which induces cell-cycle arrest and apoptosis upon CD30 binding and internalization. 2, 3

Primary Indications in T-Cell Lymphomas

CD30+ Cutaneous T-Cell Lymphoma (CTCL)

BV is recommended for advanced stage refractory or relapsed CD30+ CTCL, including both primary cutaneous anaplastic large cell lymphoma (pcALCL) and mycosis fungoides/Sézary syndrome (MF/SS). 1

• For pcALCL with extensive cutaneous disease or systemic progression, combination chemotherapy or brentuximab is appropriate. 1
• BV demonstrates an overall response rate of 73% (95% CI: 60-86%) and complete response rate of 35% (95% CI: 22-49%) in CD30+ cutaneous lymphoproliferative disorders. 4
• The standard dosing is 1.8 mg/kg intravenously every 21 days for up to 16 cycles. 4, 5

Systemic Anaplastic Large Cell Lymphoma (ALCL)

Brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, prednisone) is included as preferred first-line therapy for patients with ALCL (category 1 evidence). 1

• For other CD30-positive peripheral T-cell lymphoma histologies, BV + CHP is category 2A. 1
• In palliative/relapsed settings, brentuximab vedotin is the preferred single-agent regimen for ALCL. 1

Hodgkin Lymphoma

BV is FDA-approved and highly effective for relapsed/refractory Hodgkin lymphoma after autologous stem cell transplantation. 1, 2

• BV is being incorporated into frontline therapy combinations, with AAVD (brentuximab, adriamycin, vinblastine, dacarbazine) showing promising results. 1
• For first relapse, BV combinations with bendamustine or checkpoint inhibitors are under active investigation. 1

Critical Clinical Considerations

CD30 Expression Levels

Responses occur across all levels of CD30 expression, including patients with very low (<10%) or absent CD30 expression. 1

• In MF/Sézary syndrome, overall response rates are 50% with low CD30 expression (<10%), 58% with medium expression (10-50%), and 50% with high expression (≥50%). 4
• Interpretation of CD30 expression is not universally standardized, and responses have been observed even with minimal CD30 positivity. 1

Peripheral Neuropathy Management

Grade 1-2 peripheral neuropathy occurs in 65% of patients and is the most common dose-limiting toxicity. 4

• Neuropathy resolves in 45% of patients with a median time to resolution of 41.5 weeks. 4
• Dose reduction to 1.2 mg/kg should be instituted for grade 2 neuropathy. 4
• Monitor patients closely at each visit for sensory symptoms, and do not dismiss early complaints as this toxicity can become debilitating if BV is continued at full dose. 4

Other Significant Adverse Events

Grade 3-4 events include neutropenia, nausea, chest pain, deep vein thrombosis, transaminitis, and dehydration, though these occur less frequently than neuropathy. 4

Bridging to Stem Cell Transplantation

BV serves as an effective bridge to allogeneic stem cell transplantation in eligible patients with MF/SS who have refractory disease. 1

This strategy is particularly valuable in relatively young patients with progressive Sézary syndrome where allogeneic transplant should be considered despite the optimal conditioning regimen and timing remaining undefined. 1

Comparative Efficacy in Specific Subtypes

• Lymphomatoid papulosis: 100% response rate (9/9 patients) with time to response of 3 weeks and median duration of 26 weeks. 4
• Primary cutaneous ALCL: 100% response rate (2/2 patients). 4
• Mycosis fungoides: 54% response rate (15/28 patients), independent of CD30 expression level. 4
• Angioimmunoblastic T-cell lymphoma: 54% overall response rate. 6
• Peripheral T-cell lymphoma NOS: 33% overall response rate. 6

Common Pitfall to Avoid

Do not withhold BV from patients with low or undetectable CD30 expression in MF/SS, as clinical efficacy has been demonstrated across all expression levels, and the mechanism may involve bystander effects beyond direct CD30 targeting. 1, 4