Prolonged Treatment with Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL),
Authors: Forero-Torres Andres , Berryman R. Brian , Advani Ranjana H. , Bartlett Nancy L. , Chen Robert W. , Fanale Michelle A. , Gopal Ajay K. , O'Connor Owen A. , Olshefski Randal , Smith Scott E. , Grove Laurie E. , Matous Jeffrey 
Published: October 2019

Abstract
Abstract 3711

Background:
Brentuximab vedotin (SGN-35) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). Trials with brentuximab vedotin have previously reported results in patients with relapsed or refractory HL or sALCL. In a pivotal HL trial, complete remissions (CRs) were observed in 35 of 102 patients (34%) with a median duration of 20.5 months (Chen 2011). Thirty-three of 58 patients (57%) with sALCL achieved CRs with a median duration of 13.2 months in a phase 2 trial (Pro 2011). In both of these studies, a maximum of 16 cycles was permitted; patients with HL received a median of 10 cycles and those with sALCL, 7 cycles. This case series presents a retrospective analysis on a subset of patients who have received prolonged treatment (>16 cycles) with brentuximab vedotin in a treatment-extension study (ClinicalTrials.gov #NCT00947856).

Methods:
Brentuximab vedotin 1.2 or 1.8 mg/kg was administered every 3 weeks as a 30-minute outpatient IV infusion for up to 16 cycles of treatment in 1 of 4 preceding studies. Consecutive cycles of treatment were then administered in the extension study until disease progression, unacceptable toxicity, or withdrawal of consent. Antitumor activity in this case series was based on objective response assessments per the investigator according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).

Results:
Fifteen patients have received >16 consecutive cycles of treatment with brentuximab vedotin. The median age of patients was 35 years (range 14–74); 9 patients were female. Patients had relapsed or refractory CD30-positive HL (10) or sALCL (5) and had received a median of 3 prior therapies (range 1–14). Nine patients had previously failed autologous stem cell transplant (SCT), and 2 of these patients had additionally failed an allogeneic SCT. The median number of treatment cycles was 19 (range 17–29). At the time of the analysis, 2 patients had discontinued treatment; neither patient had discontinued due to an adverse event (AE). AEs among patients were generally mild, which enabled continued treatment beyond the initial study. Across all cycles of treatment, AEs in >30% of patients were peripheral sensory neuropathy (73%), fatigue (53%), upper respiratory tract infection (53%), cough (40%), alopecia, diarrhea, neutropenia, and pyrexia (33% each). The only AE which occurred for the first time after Cycle 16 in more than 1 patient was neutropenia (n=2). Peripheral neuropathy events (by Standardised MedDRA Query) of Grade 1 or 2 were experienced by 87% of patients; no Grade 3 or 4 events of peripheral neuropathy were observed. Peripheral neuropathy was managed with dose reductions and dose delays; resolution or improvement of peripheral neuropathy was observed in over half of the patients (7 of 13) with a median time to resolution or improvement of 3.1 weeks (range 0.1–8). Best clinical responses in patients were 11 CRs, including CRs achieved by all 5 patients with sALCL, 2 partial remissions (PRs), and 2 patients with stable disease. Four of 11 patients evolved from a PR to achieve a CR; the median time from first dose to achievement of CR was 12 weeks (range 5.4–48.9). The median duration of objective response has not been reached; the durations ranged from 6.5+ to 21.8+ months. At the time of the analysis, 14 patients were alive and free of documented progression, and the median progression-free survival had not been reached (range 11.8+ to 23+ months).

Conclusions:
Among patients with relapsed or refractory HL or sALCL who have enrolled in a treatment-extension study, 15 have received >16 consecutive cycles of treatment with brentuximab vedotin. The safety profile of brentuximab vedotin did not meaningfully change with treatment beyond 16 cycles. Durations of response (11 CR and 2 PR) ranged from 6.5+ to 21.8+ months, with 13 patients still receiving treatment. Updated safety and durability of response will be presented at the meeting.

Disclosures:
Forero-Torres: Seattle Genetics, Inc.: Research Funding. Off Label Use: Brentuximab vedotin (SGN-35) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). It is an investigational agent that is being studied in CD30+ malignancies. Berryman:Seattle Genetics, Inc.: Research Funding; Soligenix: Research Funding; Gloucester Pharmaceuticals: Research Funding. Advani:Seattle Genetics, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bartlett:Seattle Genetics, Inc.: Consultancy, Research Funding, Travel Expenses. Chen:Seattle Genetics, Inc.: Consultancy, Research Funding, Travel Expenses. Fanale:Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gopal:Seattle Genetics: Consultancy, Honoraria, Research Funding; Millennium: Honoraria, Speakers Bureau; Cephalon: Research Funding; Spectrum: Research Funding; Piramal: Research Funding; Merck: Research Funding; Calistoga: Research Funding; Abbott: Research Funding; Pfizer: Research Funding; SBIO: Research Funding; Gilead: Research Funding; Genzyme: Speakers Bureau; Amgen: Speakers Bureau; Cellular Therapeutics Inc.: Speakers Bureau. O'Connor:Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Allos: Consultancy, Research Funding; Purdue Pharma: Consultancy; Celgene: Consultancy; Merck: Research Funding. Olshefski:Seattle Genetics, Inc.: Research Funding. Smith:Seattle Genetics, Inc.: Research Funding; Cephalon: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Spectrum: Consultancy; GSK: Speakers Bureau. Grove:Seattle Genetics, Inc.: Equity Ownership; Seattle Genetics, Inc.: Employment. Matous:Seattle Genetics, Inc.: Research Funding; Celgene: Speakers Bureau; Cephalon: Speakers Bureau; Millennium: Speakers Bureau.