Barrington, S

Collins, G

Davies, A

Gibb, Adam

Linton, Kim

McKay , P

Menne, T

Miall, P

Nagy, E

Paterson, K

Pirrie, Sarah

Radford, J

Warbey, V

Wheatley , K

English

P002: Introduction. Results of standard treatment for older patients (pts) withclassical Hodgkin lymphoma (cHL) are sub-optimal and alternativeapproaches are required. Brentuximab vedotin (BV) is a CD30 targetedantibody-drug conjugate which in the pivotal* phase 2 trial inrelapsed/refractory cHL produced an objective response rate of 75%,complete remission rate of 34% and manageable toxicity. BREVITY isa study of efficacy/tolerability of BV in older, frail or comorbid pts withpreviously untreated cHL. Methods. This was a phase II, Simon 2-stage,single arm study requiring 30 evaluable pts. Primary outcome was completemetabolic response rate (CMR, Deauville Score 1-3) by centrallyreviewed PET-CT after 4 cycles of BV. Secondary outcomes includedPFS, OS, toxicity and comorbidity assessment (CIRS-G). Inclusion criteriawere previously untreated cHL stage 2 (with B symptoms and/ormediastinal bulk) or stages 3/4 with cardiac/respiratory compromise(at any age) or an ECOG score 1-3 and considered unfit for standardchemotherapy (in pts ≥60 yrs). BV dose was 1.8 mg/kg every 3 weeks,reduced to 1.2 mg/kg for toxicity. Pts in CMR/PMR after 4 doses BVcontinued to a total of 16 cycles if CT and/or PET-CT every 4 cyclesconfirmed ongoing response. PFS/OS data is not mature. Results. 38 ptswere recruited Feb 2014-Oct 2015 at 12 UK centres; demographics areshown in Table 1.Table 1.35 pts were treated and evaluable for toxicity, 31 are evaluable forresponse. Median follow-up for alive pts is 11.6(range 0.9, 21.4) months.A median of 4 cycles were given per pt (range 1, 16). 28(12%) cycles in14 pts were modified due to toxicity and 11 pts stopped treatment dueto adverse events (AEs). 695 AEs were reported of which 601(86%)were grade 1/2. 26(74%) pts had at least 1 AE ≥grade 3, most commonlyinfection, myelosuppression or neuropathy. CMR rate at PET4 was25.8%(95% CI 13.7, 43.2) and combined CMR/PMR rate was83.7(95%CI: 67.4, 92.9). To date 21(67.7%) pts have progressed. Discussion.In this study BV monotherapy produced a high objectiveresponse rate although the CMR rate after 4 cycles did not meet thepre-specified 40% level. Toxicity was greater than in the pivotal* studywhere pts were younger/fitter and led to treatment termination in somepts. Nevertheless BV is effective in this older comorbid population. Afollow-on study incorporating BV at lower dose in combination withother agents and growth factor support aimed at improving the CMRrate is in development

The University of Manchester - Institutional Repository

Preliminary results of a phase II study of brentuximab vedotin using a response adapted design for the first line treatment of patients with Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or co-morbidity (BREVITY)

https://pure.manchester.ac.uk/ws/files/52064550/Haematologica_101_1_80.pdf

Preliminary results of a phase II study of brentuximab vedotin using a response adapted design for the first line treatment of patients with Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or co-morbidity (BREVITY)

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