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The PAD (Ireland) study for patients with refractory and relapsed myeloma – an update

ICORG would like to highlight an abstract relating to an ICORG in-house study, The PAD (Ireland) Study for Patients with Refractory and Relapsed Myeloma (ICORG 05-01) which was presented at the 12th International Myeloma Workshop, which took place in Washington, USA, from 26th February to 1st March 2009.

The PAD (Ireland) study for patients with refractory and relapsed myeloma – an update.

Morris T.C.M.1, Kettle P.J.1 Drake, M.1, Brunton A.2, Cook G.3, Leahy, M4, O’Dwyer M.5, Murray, M 5, Enright H.6, McCloy, M.7 O’Gorman, P 7 Yong, K.8O’Shea T.9, Popat R.10, Oakervee, H.10 Cavenagh J.10 1Department of Haematology, Belfast City Hospital. 2Clinical Trials Unit, Belfast City Hospital. 3Department of Haematology, St James’s University Hospital, Leeds. 4Department of Haematology, Limerick General Hospital. 5Department of Haematology, University College Hospital Galway. 6Department of Haematology, Tallaght Hospital, Dublin. 7Department of Haematology, The Mater Misericordiae Hospital, Dublin. 8 Department of Haematology, University College London. 9All Ireland Cooperative Oncology Research Group (ICORG). 10 Department of Haematology, St Bartholomew’s Hospital, London.

Introduction: The combination of Bortezomib with Adriamycin/Dexamethasone (PAD) is a highly effective induction agent with response rates of up to 95% (Oakervee et al, BJH 2005; 129: 755-62). We postulated that the superior efficacy of PAD chemotherapy could be demonstrated by studying patients who have been previously treated with VAD or a VAD-like regimen (VAMP, C-VAMP, Z-DEX etc.) by comparing the response to PAD given following relapse to the response previously obtained with the VAD or VAD-like regimen.

Materials and Methods: A Phase II study was developed with three cohorts, each planned to recruit 23 patients. Cohort 1; patients treated with VAD or VAD-like regimen who previously had an autologous transplant; Cohort 2 – similar patients but without previous transplant and Cohort 3 – patients refractory to VAD. Patients in groups 1 and 2 were allowed to have received one further line of treatment following VAD but patients in group 3 would proceed directly to PAD.

Results: Cohort 1 has been fully recruited. 8 patients achieved CR following PAD compared to 3 post-VAD p=0.013 using McNemar’s Chi-squared test with continuity correction. Comparison of the fall in paraprotein showed a median fall of 89% post-PAD compared to 60% post-VAD, (p<0.003) Wilcoxon Matched Pairs Rank Test. There were no reports of increased cardiotoxicity. A number of patients proceeded on to second transplant following their response to PAD therapy. 6 patients have been recruited to group 2 and responses appear similar to patients in group 1. 18 patients have been recruited to group 3. In these patients, refractory to VAD-type chemotherapy nine of twelve currently evaluable patients have shown superior responses compared to a VAD-type chemotherapy. These results will be updated to include all currently enrolled patients and presented in detail.

Conclusion: PAD is a highly active therapy for patients with relapsed or refractory myeloma. The study provides supportive evidence for the use of PAD re-induction prior to second autologous transplantation currently being investigated in a randomised controlled clinical trial (NCRI UK) Myeloma X.