Stanford Cancer Institute, Stanford, CA
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
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) | |
CD30=10% | 8 | 5 (63) | 0 | |
PTCL-NOS | CD30 >median | 14 | 8 (57) | 2 (14) |
CD30 ≤ median | 14 | 10 (71) | 2 (14) | |
CD30=10% | 6 | 4 (67) | 2 (33) |
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