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 brentuximab vedotin by CD30 expression: Results from five trials in PTCL, CTCL, and B-cell lymphomas.
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #297)
J Clin Oncol 37, 2019 (suppl; abstr 7543)
Author(s): Deepa Jagadeesh, Steven M. Horwitz, Nancy L. Bartlett, Ranjana H. Advani, Eric D. Jacobsen, Madeleine Duvic, Ashish Gautam, Shangbang Rao, Matthew Onsum, Michelle Fanale, Youn H. Kim; Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland, OH; Memorial Sloan Kettering Cancer Center, New York, NY; Washington University School of Medicine in St. Louis and Siteman Cancer Center, St. Louis, MO; Stanford Cancer Institute, Stanford, CA; Dana-Farber Cancer Institute, Boston, MA; The University of Texas MD Anderson Cancer Center, Houston, TX; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA; Seattle Genetics Inc, Bothell, WA; Seattle Genetics, Bothell, WA; Seattle Genetics, Inc, Bothell, WA; Department of Dermatology, Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA
Background: Brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, has been evaluated in multiple trials in patients (pts) with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell lymphoma. We examined the ability of CD30 expression level to predict response to BV across these patient populations. Methods: Data were integrated from 275 pts with PTCL, CTCL, and B-cell lymphoma treated with BV from 5 prospective clinical trials. Study SGN35-012 evaluated BV plus rituximab or BV monotherapy in pts with relapsed/refractory non-Hodgkin lymphoma. The ALCANZA study compared BV to physician’s choice of methotrexate or bexarotene in pts with mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL). Three investigator-sponsored trials evaluated BV monotherapy in pts with relapsed PTCL, MF, and pcALCL (35-IST-030, 35-IST-001, 35-IST-002). Exploratory analyses were conducted to examine the relationship between CD30 expression and objective response rate (ORR) for pts with CD30 expression ≥10%, <10%, or undetectable (0%) by IHC (malignant cells or lymphoid infiltrate; local review). Results: 143 pts had tumors with CD30 <10%, including 58/143 with undetectable CD30. Activity with BV was observed at all levels of CD30 expression, including CD30=0 (Table). Analysis of the interaction between CD30 and duration of response is ongoing and will be presented in the final poster. ORR by CD30 expression, n/N (%). Clinical trial information: NCT01421667, NCT02588651, NCT01578499, NCT01352520, NCT01396070Conclusions: CD30 expression levels ≥10%, <10%, or undetectable did not predict response to BV in a range of CD30-expressing lymphomas: Clinical responses occurred in pts with CD30 low and CD30 undetectable lymphomas. Limitations of IHC, the dynamic nature and heterogeneity of cell-surface CD30 expression, and multiple mechanisms of action of BV may all contribute to this observation.
|PTCL||SGN35-012||10/22 (45)||4/12 (33)||2/6 (33)|
|35-IST-030*||NA||4/6 (67)||1/2 (50)|
|CTCL (MF)||ALCANZA||20/28 (71)||12/22 (55)||NA|
|35-IST-001||11/20 (55)||11/20 (55)||NA|
|35-IST-002||12/15 (80)||9/17 (53)||NA|
|B-cell lymphoma||SGN35-012||17/47 (37)||24/66 (36)||17/50 (34)|
NA=not applicable *interim analysis of non-registrational study