Blood (ash annual meeting abstracts) 2007 110: abstract 2724

Blood (ASH Annual Meeting Abstracts) 2007 110: Abstract 2724
200Poster Session
Myeloma: Relapsed and Refractory Multiple Myeloma
Myeloma - Therapy, excluding Transplantation
PAD Given at Relapse Is More Effective Than VAD
Given as Induction Therapy - Results of a Phase II
Study.
Treen C. Morris1, Paul J. Kettle1, Mary B. Drake1, Aisleen Brunton2,*, Gordon
Cook3, Maeve Leahy4,*, Michael O’Dwyer5, Helen Enright6, Tanya O’Shea7,*,
Rakesh Popat8,*, Heather Oakervee8,* and James D. Cavenagh8
1 Haematology, Belfast City Hospital, Belfast, United Kingdom; 2 Clinical Trials Unit, Belfast City Hospital, Belfast, United Kingdom; 3 Haematology, St James’ University Hospital, Leeds, United Kingdom; 4 Haematology, Limerick General Hospital, Limerick, Ireland; 5 Haematology, University College Hospital, Galway, Ireland; 6 Haematology, Tallaght Hospital, Dublin, Ireland; 7 All-Ireland Cooperative Oncology Research Group (ICORG), Ireland and 8 Haematology, St Bartholomew’s Hospital, London, United Kingdom. Abstract
Introduction: The combination of Vincristine, Adriamycin and Dexamethasone
(VAD) followed by autologous transplantation has been a standard of care for patients
with Myeloma for a number of years. Recently, it has been shown that a 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, in
terms of both relative and absolute changes in the paraprotein or light chains and the
degree of remission obtained by the standard EBMT criteria.
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. A total of 42 patients
have been recruited and as recruitment to cohort 1 is now complete, this report will
focus on these 23 patients.
Results: 23 patients in Cohort 1 (9 females, 14 males) had a median age of 60 years
(range 41–73). 8 patients had received thalidomide-based regimens following relapse
after transplantation and had relapsed again. 15 patients were in first relapse. The time
from diagnosis to PAD chemotherapy was 46 months (18–179 months). Previous
treatment given was VAD 13, C-VAMP 5, C-VAD 3, Z-DEX 2. Patients received a
median of four cycles of PAD. 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. This difference was significant by the Wilcoxon
Matched Pairs Rank Test (p<0.003). There were no reports of increased
cardiotoxicity. A number of patients proceeded on to second transplant following their
response to PAD therapy.
Conclusion: PAD is a highly active therapy for patients with myeloma in relapse,
even if they have received a prior VAD or VAD-like regimen the differences are
statistically significant despite the fact the patients have all experienced at least one
relapse. PAD therapy will be incorporated into the NCRI (UK) Myeloma X regimen
as an induction therapy in patients who have relapsed post autologous transplantation,
with patients randomised to consolidation with a second autologous transplant or
conventional dose cyclophosphamide.
Footnotes
Disclosure: Research Funding: Study funded by Jansen-Cilag UK through the All-
Ireland Cooperative Oncology Research Group (ICORG). Honoraria Information:
TCM has received Honoraria from Jansen-Cilag as a speaker (less than US $10,000).
Off Label Use: Information is provided on the combination of Bortezomib with
Adriamycin and Dexamethasone.

Source: http://www.icorg.ie/images/uploads/file/publications/PADPosterASHNov2007.pdf