2019 ASCO Annual Meeting!
Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Type: Poster Session
Time: Monday June 3, 8:00 AM to 11:00 AM
Location: Hall A
Response to A+CHP by CD30 expression in the ECHELON-2 trial.
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #292)
J Clin Oncol 37, 2019 (suppl; abstr 7538)
Author(s): Ranjana H. Advani, Steven M. Horwitz, Swaminathan Padmanabhan Iyer, Nancy L. Bartlett, Won Seog Kim, Herve Tilly, David Belada, Tatyana Feldman, Árpád Illés, Eric D. Jacobsen, Andreas Huettmann, Pier Luigi Zinzani, Owen A. O'Connor, William L. Trepicchio, Harry H. Miao, Shangbang Rao, Matthew Onsum, Thomas John Manley, Tim Illidge; Stanford Cancer Institute, Stanford, CA; Memorial Sloan Kettering Cancer Center, New York, NY; MD Anderson Cancer Center/University of Texas, Houston, TX; Washington University School of Medicine in St. Louis and Siteman Cancer Center, St. Louis, MO; Sungkyunkwan University School of Medicine, Samsung Medical Center, Division of Hematology and Oncology, Seoul, South Korea; Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen, France; Fourth Department of Internal Medicine-Haematology, Charles University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic; Hackensack University Medical Center, Hackensack, NJ; University of Debrecen, Department of Hematology, Debrecen, Hungary; Dana-Farber Cancer Institute, Boston, MA; Essen University Hospital, Essen, Germany; Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy; Columbia University Medical Center, New York, NY; Millennium Pharmaceuticals, Inc., Cambridge, MA; Takeda Pharmaceutical Company, Cambridge, MA; Seattle Genetics Inc, Bothell, WA; Seattle Genetics, Bothell, WA; Seattle Genetics, Inc., Bothell, WA; University of Manchester, Manchester, United Kingdom
Background: Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30. The ECHELON-2 (E-2) study demonstrated significantly longer progression-free and overall survival with BV plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP in frontline treatment of patients (pts) with CD30+ peripheral T-cell lymphoma (PTCL). Complete remission (CR) rate (A+CHP 68%; CHOP 56%) and objective response rate (ORR) (A+CHP 83%; CHOP 72%) were also significantly increased. Expression of CD30 is universal in systemic anaplastic large-cell lymphoma (sALCL) but variable among non-sALCL subtypes. As ORR is a direct measure of antitumor activity, we examined response to A+CHP by CD30 expression. Methods: Pts with CD30+ (≥10% by local review) PTCL were included in E-2. Eligible histologies included ALK+ sALCL (IPI ≥2), ALK− sALCL, PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukemia/lymphoma, enteropathy-associated T-cell lymphoma, and hepatosplenic T-cell lymphoma. We analyzed the relationship between CD30 expression (IHC Ber H2 antibody) above and below the median (median CD30=18% PTCL-NOS; 25% AITL) and CR rate, ORR, and duration of CR (DOCR) in pts with AITL and PTCL-NOS treated with A+CHP. Results: Most (26/29, 90%) AITL pts had CD30 expression between 10% and 30%. PTCL-NOS pts were more evenly distributed across levels of CD30 expression ranging from 10% to 100%. CD30 levels were neither predictive of response (Table) nor significantly associated with DOCR in pts with AITL (P=0.30) or PTCL-NOS (P=0.90) (log-rank test). Response by CD30 expression. Clinical trial information: NCT01777152Conclusions: CD30 expression above vs below median (or at 10%) did not predict response to A+CHP in E-2 non-ALCL subtypes, as responses were seen across CD30 levels. This may be due to intra- and inter-tumoral heterogeneity of CD30 expression, limitations of IHC, the nature of CD30 on the cell surface, and multiple mechanisms of action of BV. Further evaluation of the expression-response relationship in PTCL pts with CD30 <10% is warranted.
|CD30||Pts, n||CR, n (%)||PR, n (%)|
|AITL||CD30 >median||14||8 (57)||1 (7)|
|CD30 ≤ median||15||8 (53)||3 (20)|
|PTCL-NOS||CD30 >median||14||8 (57)||2 (14)|
|CD30 ≤ median||14||10 (71)||2 (14)|
|CD30=10%||6||4 (67)||2 (33)|