Background

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL) characterized by a follicular helper T-cell phenotype. The standard frontline treatment for AITL typically involves CHOP or CHOP-like regimens, with consideration for autologous stem cell transplant. A promising treatment option for CD30-positive (CD30+) PTCLs, including AITL, is the anti-CD30 antibody drug conjugate, brentuximab vedotin (BV). The ECHELON-2 study demonstrated equivocal outcomes in CD30+ PTCL patients (pts) who received BV-CHP instead of CHOP. However, response of BV in CD30+ AITL pts is still uncertain. This study aims to evaluate the relationship between CD30 expression and the clinical response to BV in pts diagnosed with AITL.

Methods

This retrospective IRB approved study conducted at MD Anderson Cancer Center, where we analyzed pts with AITL diagnosed between 1997- 2023. Patient demographics, laboratory data at diagnosis, pathology review, treatment, and treatment response were collected and analyzed. Expression of CD30 expression in neoplastic cells was evaluated by immunohistochemistry and scored in 5% increments. Kaplan- Meier method was used to assess overall survival (OS) and log-rank used to compare different groups.

Results

This study included a cohort of 339 pts with AITL. Among them, 55 (23%, n=237) had no detectable CD30 expression (CD30=0%),182 (77%, n=237) patients had detectable CD30 expression (CD30>1%), and 102 pts had unknown CD30 expression. Table 1 shows patient characteristics by CD30 expression and response to first-, second-, and third- line BV treatment. There were 113 (48%, n=237) females and 124 (52%, n=237) males with a median age of 66 years. Most patients were Whites (88%, n=196) followed by Black (4%, n=196), and Asian (5%, n=196). Fifty-two (n=122) of pts who were CD30+ had stage III, 43% (n=122) had stage IV (p-value= <0.001), and 38% had BM involvement (p- value= 0.3). For pts with disease showing no CD30 expression (CD30neg) 16% (n=43) of pts had stage III, 70% (n=43) had stage IV, and 48% (n=42) had BM involvement. Auto-Stem cell transplant (ASCT) was performed in 48% of those with CD30+ and 43% of CD30neg. The most common first-line treatment was chemotherapy combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by other CHOP like regimens. In total, 35 pts received BV treatment as first-line, 32 patients received BV in combination with chemotherapy and 3 received BV only. For second-line treatment, 11 received BV treatment and for third- line only 6 received BV. First- line treatment with BV showed better clinical response rates, with 82% achieving complete response (CR, n= 34), followed by second line CR with 56% (n= 9) and third- line with 0% (n= 6). The median OS were similar between those with CD30+ who did or did not receive first line BV (20 months vs. 19 months, p>0.05). The median OS for CD30neg pts who did not receive BV was 25 months (p=0.42). Furthermore, there was no statistically significant difference in OS between pts who underwent a ASCT (CD30+ 24.5 months and CD30neg 32.5 months, respectively) and those who did not (CD30+ 18.5 months and CD30neg 24.5 months, respectively, p- value = 0.29).

Conclusion

While this study did not find CD30 expression to be a predictor of response to BV treatment or ASCT in AITL pts, it provides valuable insights into the prevalence of CD30 expression and BV response as first- line treatment. Notably, 77% of pts had CD30 expression and pts who received BV as first- line had a higher proportion of CRs compared to pts who received BV as second- and third- line treatments. Further investigations with larger patient cohorts are necessary to determine the prognostic and predictive role of CD30 in AITL. Additional studies analyzing CD30 expression levels in malignant cells, immunoblasts, and macrophages are planned for presentation at the upcoming annual meeting.

Lee:Aptitude Health: Honoraria; Takeda: Research Funding; Cancer Experts: Honoraria; Century Therapeutics: Consultancy; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Seagen Inc.: Research Funding; Pharmacyclics: Research Funding; Oncternal Therapeutics: Research Funding; Olson Research: Honoraria; Korean Society of Cardiology: Honoraria; Janssen: Honoraria; Guidepoint: Honoraria; Deloitte: Honoraria; Curio Sciences: Honoraria. Flowers:Karyopharm: Consultancy; Cellectis: Research Funding; Genmab: Consultancy; Genentech Roche: Consultancy, Research Funding; Novartis: Research Funding; Burroghs Wellcome Fund: Research Funding; Acerta: Research Funding; Pharmacyclics: Research Funding; Xencor: Research Funding; Pharmacyclics Jansen: Consultancy; Ziopharm: Research Funding; Pfizer: Research Funding; Bayer: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Nektar: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Research Funding; Amgen: Research Funding; Morphosys: Research Funding; Beigene: Consultancy; Iovance: Research Funding; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Kite: Research Funding; Jannsen Pharmaceuticals: Research Funding; Spectrum: Consultancy; Gilead: Consultancy, Research Funding; Adaptimmune: Research Funding; Allogene: Research Funding; Abbvie: Consultancy, Research Funding; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; 4D: Research Funding; Sanofi: Research Funding; Guardant: Research Funding; SeaGen: Consultancy; Cancer Prevention and Research Institute of Texas: Research Funding; CPRIT Scholar in Cancer Research: Research Funding. Neelapu:Precision Biosciences: Research Funding; Immunoadoptive Cell Therapy Private Limited: Consultancy, Other: Scientific Advisory Board; Carsgen: Consultancy; Bluebird Bio: Consultancy, Other: Advisory board member; Fosun Kite: Consultancy, Other: Advisory board member; Athenex: Consultancy, Other: Advisory board member; N/A: Patents & Royalties: Related to cell therapy and the safety switch described (intellectual property); Sellas Life Sciences: Consultancy, Other: Advisory board member; Incyte: Consultancy, Other: Advisory board member; Caribou: Consultancy, Other: Advisory board member; Longbow Immunotherapy: Current holder of stock options in a privately-held company; Kite, A Gilead Company: Consultancy, Other: Advisory Board Member, Research Funding; Chimagen: Consultancy, Other: Advisory board member; Bristol Myers Squibb: Consultancy, Other: Advisory Board Member, Research Funding; Sana Biotechnology: Consultancy, Other: Advisory board member, Research Funding; Orna Therapeutics: Consultancy, Other: Advisory board member; Janssen: Consultancy, Other: Advisory board member; Synthekine: Consultancy, Other: Advisory board member; Takeda: Consultancy, Other: Advisory board member; Merck: Consultancy, Other: Advisory Board Member; Morphosys: Consultancy, Other: Advisory board member; Adicet Bio: Consultancy, Other: Advisory board member, Research Funding; Allogene: Consultancy, Other: Advisory board member, Research Funding; Astellas Pharma: Consultancy, Other: Advisory board member. Vega:Allogene: Research Funding; Geron: Research Funding. Iyer:Seagen: Consultancy, Research Funding; Merck: Research Funding; CRISPR: Consultancy, Research Funding; Innate: Research Funding; Acrotech: Consultancy, Research Funding; Legend: Research Funding; Astra Zeneca: Research Funding; Ono: Research Funding; Pfizer: Research Funding; Salarius: Consultancy; Drenbio: Research Funding; Yingli: Consultancy, Research Funding; CuraBio: Speakers Bureau; American Society of Hematology: Speakers Bureau; American Society of Transplant and Cellular Therapy: Speakers Bureau.

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2023
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