Results of a phase II study of brentuximab vedotin in the first line treatment of Hodgkin lymphoma patients considered unsuitable for standard chemotherapy (BREVITY)

A. Gibb, S. Pirrie, K. Linton, K. Paterson, A. Davies, G. Collins, T. Menne, P. McKay, P. Fields, F. Miall, E. Nagy, K. Wheatley, V. Warbey, S. Barrington, J. Radford

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Abstract

Introduction: Standard treatment for Hodgkin lymphoma (HL) is poorly tolerated in older patients and results are disappointing. Brentuximab vedotin (BV) is a CD30 targeted antibody‐drug conjugate licenced for the treatment of relapsed or refractory HL on the basis of excellent safety and efficacy demonstrated in the pivotal phase 2 clinical trial. BREVITY trial was designed to evaluate the efficacy and tolerability of BV monotherapy in previously untreated patients (pts) with HL unfit for standard treatment due to age, frailty or co‐morbidity. Methods: This response adaptive phase II, Simon 2‐stage, single arm study required 30 evaluable pts. Primary outcome was complete metabolic response (CMR, Deauville Score 1‐3) by centrally reviewed PET‐CT after 4 cycles of BV. Secondary outcomes included PFS, OS, toxicity and comorbidity assessment (CIRS‐G). Inclusion criteria were previously untreated HL stage 2 (with B symptoms and/or mediastinal bulk) to stage 4 with cardio‐respiratory compromise (at any age), or ECOG PS ≤3 and considered unfit for standard chemotherapy (in pts ≥60 yrs). BV dose was 1.8 mg/kg every 3 weeks, reduced to 1.2 mg/kg for toxicity. Pts responding after 4 doses of BV continued to a maximum of 16 cycles if CT/PET‐CT every 4 cycles confirmed ongoing response. Pts also underwent exploratory blinded PET‐CT after cycle 2. Results: 38 pts were recruited from Feb 2014‐Oct 2015 at 12 UK centres; demographics are shown in Table 1. 35 treated pts were evaluable for toxicity, 31 were evaluable for response. A median of 4 cycles was given (range 1‐16). Dose was reduced in 28 cycles across 14 pts due to toxicity and 11 pts stopped treatment due to adverse events (AEs). 716 AEs were reported, 626 (88%) were grade 1/2. 27 (77%) pts had at least one AE ≥ grade 3, most commonly infection, myelosuppression or neuropathy. CMR at PET4 was 26% (95% CI 14, 43) and overall objective response was 84% (95%CI: 67, 93). There was a significant correlation of interim PET2 with PET4 (Rho = 0.67, p < 0.001) with a CMR rate at PET 2 of 32% (95% CI 17, 52). To date 28 of 31 evaluable pts have progressed and median PFS is 7.4 months (95% CI 5.3, 10.2). Conclusions: In this study BV monotherapy produced a high overall response rate although the CMR rate after 4 cycles did not meet the pre‐specified 40% level, and PFS was short. Toxicity was greater than in the pivotal study in a younger/fitter population and led to treatment termination in some pts. A follow‐on study aims to improve CMR and PFS by using a lower dose of BV in combination with other agents. Table 1Patient Characteristicn=38 Median (Range)Age 76 (59, 90) CIRS‐G ScoreNo. categories endorsed Severity Total score 3 (0, 7) 1.5 (0, 3) 6 (0, 11) n (%) GenderMale Female 22 (57.9) 16 (42.1) StageStage 2 Stage 3 Stage 4 7 (18.4) 13 (34.2) 18 (47.4) B symptoms 27 (71.1) Bulky Disease 5 (13.2) Extranodal disease 22 (57.9) ECOG Performance Status0 1 2 3 4 3 (7.9) 16 (42.1) 11 (28.9) 7 (18.4) 1 (2.6)
Original languageEnglish
Pages (from-to)80-81
Number of pages2
JournalHematological oncology
Volume35
Issue numberS1
DOIs
Publication statusPublished - 7 Jun 2017

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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