Peripheral T-cell lymphoma (PTCL) encompasses a diverse and aggressive group of lymphomas arising from mature T-cells and natural killer (NK) cells, representing 12–15% of all non-Hodgkin lymphomas worldwide. While CD30 expression varies among PTCL subtypes, it is a key diagnostic marker in systemic anaplastic large cell lymphoma (sALCL). Notably, PTCL-NOS cases exhibit CD30 expression in about 40% to 60% of instances, with implications for patient outcomes. As per DelveInsight’s estimates, the United States accounted for approximately 12,000 incident cases in 2023, whereas Japan accounted for around 8,000 incident cases of PTCL. Among all the subtypes of PTCL, PTCL- NOS, Angioimmunoblastic T-cell lymphoma (AITL), and  Anaplastic Large-Cell Lymphoma (ALCL) contribute majorly in decreasing order.

Treatment for PTCL aims for a cure and typically includes combination chemotherapy regimens like CHOP or EPOCH, along with localized radiotherapy, stem cell transplants, and steroid therapy. CHOP remains the gold standard for PTCL patients, but there is a significant unmet need for those who cannot undergo this treatment. ADCETRIS (brentuximab vedotin) is currently the only approved ADC as a first-line therapy for PTCL. Seagen is conducting trials with ADCETRIS in combination with CHP and as monotherapy for patients ineligible for chemotherapy. Aside from Seagen, few companies are developing first-line therapies for PTCL.

The NCCN Guidelines recommend ADCETRIS as the preferred second-line therapy for relapsed/refractory ALCL and other CD30-positive conditions, including PTCL-NOS. ADCETRIS is a CD30-directed antibody-drug conjugate (ADC) composed of three parts: the chimeric IgG1 antibody cAC10, which targets CD30; the microtubule-disrupting agent MMAE; and a protease-cleavable linker that attaches MMAE to cAC10. The drug is currently being investigated in the Phase II SGN35-032 study for patients with peripheral T-cell lymphoma with less than 10% CD30 expression. The results presented at ASCO 2024 were as follows:

Efficacy outcomes 

• A total of 82 patients with newly diagnosed non-systemic ALCL PTCL were enrolled into the CD30 <1% and CD30 1% to <10% cohorts

• At the data cutoff of January 31, 2024, 45 of 82 patients were still in follow-up; the median follow-up time was 11.65 months

• Baseline characteristics were similar between the 2 cohorts

• The median treatment duration was 18.0 weeks 

• Among the 74 response-evaluable patients, the ORR was 80% per BICR

Safety result: 

• No new safety signals were observed, and the data were consistent with the known safety profile of A+CHP (ADCETRIS combined with cyclophosphamide, doxorubicin, and prednisone)

• Grade ≥3 treatment-emergent adverse events (TEAEs) were experienced by 46 patients

• Six patients discontinued study treatment due to TEAEs

• There were two treatment-related deaths

KOL insights

“PTCL is a heterogeneous group of malignancies where the outcomes are generally very poor. The median overall survival is 1 to 3 years [depending on] the histologic subtype, and the median 5-year OS rate is less than 25%. Many patients with PTCL have tumor cells that express CD30 depending on the histologic subtype. From experience with ADCETRIS (brentuximab vedotin), CD30 can be a very charming therapeutic target.” – MD, Samsung Medical Center and Sungkyunkwan University.

“In patients with non-sALCL PTCL with <10% CD30 expression, A+CHP as frontline therapy appears effective and has a safety profile consistent with the label.”– MD Anderson Cancer Center.

Conclusion- 

CD30 is universally expressed in sALCL and about 50% of non-sALCL subtypes, with variable expression in other subtypes—58-64% in PTCL, 43-63% in AITL, and 55% in ATLL. Brentuximab vedotin, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), is approved in the US, Europe, Canada, and other regions for treating previously untreated sALCL or more broadly for CD30-expressing PTCL, becoming a standard-of-care. The drug is currently being investigated in the Phase II SGN35-032 study for patients with peripheral T-cell lymphoma with less than 10% CD30 expression. Results presented at ASCO indicate that A+CHP is effective as frontline therapy for non-sALCL PTCL with <10% CD30 expression and has a safety profile consistent with the approved label.