Bortezomib-Based Induction Overcomes Effect of 1q Amplification On Response in Newly-Diagnosed Myeloma and Results in Similar 2 Year Event-Free Survival

Abstract

AbstractAbstract 4065 Background:Amplification of chromosome 1q occurs in 40% of myeloma and predicts lower response to induction regimens. We assessed if a PAD regimen overcomes effects of 1q amplification on overall response rate (ORR), event-free (EFS) and overall survival (OS) in newly-diagnosed, transplant-eligible myeloma. Methods:This phase II trial enrolled 107 patients, stratified by 1q amplification. All could receive 4× 21-day cycles of PAD induction: bortezomib 1.3mg/m2 D 1,4,8,11; doxorubicin 20mg/m2 D1,4; dexamethasone 20mg D1,2,4,5,8,9,11,12. Responders proceeded to melphalan 200mg/m2 and ASCT. ORR after PAD was primary endpoint. Secondary endpoints included ORR 3 monthspost-ASCT, and 2-year EFS and OS. Results:22% (20/93 evaluable cases) had amplified 1q. Median PAD cycles was4. ORRs were similar in amplified and non-amplified cases (100% vs. 87% post-PAD; 100% vs. 93% post-ASCT). After median 2 years, 2-year EFS was similar in amplified and non-amplified cases (70% vs. 75%; log-rank p=0.86), but with a trend to lower 2-year OS in amplified cases (86% vs. 94%; log-rank p=0.28). Common grade 3 or 4 adverse events included constipation (0% vs. 8% of patients), neutropenia (12% vs. 4% of patients), anaemia (4% vs. 6% of patients), back pain (4% vs. 6% of patients), neuralgia (0% vs. 6% of patients) and neuropathy (8% vs. 4%).Response levelAfter PAD induction3 months post-ASCT1q status No. evaluableNOT amplified n=63Amplified n=20NOT amplified n=58Amplified n=20ORR87%100%93%100%CR17%30%24%40%VGPR24%15%36%35%PR46%55%33%25% Conclusions:Four cycles of PAD induced high response rates in both 1q amplified and non-amplified myeloma with acceptable toxicity. After 2 years, EFS was also similar, but with a non-significant trend to lower OS in patients with 1q amplification. Funding:This study is sponsored by Janssen-Cilag Pty Ltd, Australia. Trial Registration:ACTRN12609000296235. Disclosures:Joshua:Janssen-Cilag Pty Ltd: Research Funding. Hertzberg:Janssen-Cilag Pty Ltd: Research Funding. Auguston:Janssen-Cilag Pty Ltd: Research Funding. Spencer:Novartis: Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria. Horvath:Janssen-Cilag Pty Ltd: Research Funding. Bashford:Janssen-Cilag Pty Ltd: Research Funding. Campbell:Janssen-Cilag Pty Ltd: Research Funding. Ashurst:Janssen-Cilag Pty Ltd: Employment. Wade:Janssen-Cilag Pty Ltd: Employment. Copeman:Janssen-Cilag Pty Ltd: Employment. Butcher:Janssen-Cilag Pty Ltd: Consultancy. Prince:Janssen-Cilag Pty Ltd: Research Funding.