Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas.
BACKGROUND
Hodgkin's lymphoma and anaplastic large-cell lymphoma are the two most common tumors expressing CD30. Previous attempts to target the CD30 antigen with monoclonal-based therapies have shown minimal activity. To enhance the antitumor activity of CD30-directed therapy, the antitubulin agent monomethyl auristatin E (MMAE) was attached to a CD30-specific monoclonal antibody by an enzyme-cleavable linker, producing the antibody-drug conjugate brentuximab vedotin (SGN-35).


METHODS
In this phase 1, open-label, multicenter dose-escalation study, we administered brentuximab vedotin (at a dose of 0.1 to 3.6 mg per kilogram of body weight) every 3 weeks to 45 patients with relapsed or refractory CD30-positive hematologic cancers, primarily Hodgkin's lymphoma and anaplastic large-cell lymphoma. Patients had received a median of three previous chemotherapy regimens (range, one to seven), and 73% had undergone autologous stem-cell transplantation.


RESULTS
The maximum tolerated dose was 1.8 mg per kilogram, administered every 3 weeks. Objective responses, including 11 complete remissions, were observed in 17 patients. Of 12 patients who received the 1.8-mg-per-kilogram dose, 6 (50%) had an objective response. The median duration of response was at least 9.7 months. Tumor regression was observed in 36 of 42 patients who could be evaluated (86%). The most common adverse events were fatigue, pyrexia, diarrhea, nausea, neutropenia, and peripheral neuropathy.


CONCLUSIONS
Brentuximab vedotin induced durable objective responses and resulted in tumor regression for most patients with relapsed or refractory CD30-positive lymphomas in this phase 1 study. Treatment was associated primarily with grade 1 or 2 (mild-to-moderate) toxic effects. (Funded by Seattle Genetics; ClinicalTrials.gov number, NCT00430846.).
Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. ayounes@mdanderson.org
Anas
A
Younes
Nancy L
NL
Bartlett
John P
JP
Leonard
Dana A
DA
Kennedy
Carmel M
CM
Lynch
Eric L
EL
Sievers
Andres
A
Forero-Torres
D000328:Adult; D000369:Aged, 80 and over; D000079963:Brentuximab Vedotin; D054414:Chemokine CCL17 / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D053208:Kaplan-Meier Estimate; D017730:Ki-1 Antigen; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy* / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012008:Recurrence; D012074:Remission Induction; D055815:Young Adult
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin