How to Simplify the Evaluation of Newly Introduced Chemotherapeutic Interventions in Myeloma

Authors

Treen Carson Michael Morris^{1, *,} , Mary B. Drake², Paul J. Kettle², Tracey McGuigan², Maeve Leahy³, Michael O’Dwyer⁴, Helen Enright⁵, Tanya O’Shea^6, , Rakesh Popat⁷, Heather E. Oakervee⁸, Kwee Yong⁷, Jamie D. Cavenagh⁸, David A. Cairns^9, , Alberto Alvarez-Iglesias⁴, Gordon Cook⁹

¹Centre for Cancer Research & Cell Biology, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK

²Department of Haematology, Belfast City Hospital, Lisburn Road, Belfast BT9 7AD, UK

³Department of Haematology, University Hospital Limerick, Limerick, Ireland

⁴Department of Haematology, University Hospital Galway, Newcastle Road, Galway, Ireland

⁵Department of Haematology, Tallaght Hospital, Dublin 24, Ireland

⁶Clinical Research Consulting Ltd., 16 College Square, Terenure, Dublin D6WF309, Ireland

⁷Department of Haematology, University College Hospital, London, UK

⁸Department of Haematology, St Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, UK

⁹Leeds Cancer Centre, St James’s University Hospital, Leeds LS9 7TF, UK

^*Corresponding author. Email: curlymorris_cliff@yahoo.com

DOI

10.2991/chi.k.210201.001How to use a DOI?

Keywords

Myeloma; relapse; bortezomib; adriamycin; dexamethasone; response; PAD; Myeloma X

Abstract

When the bortezomib [PS341], adriamycin and dexamethasone (PAD) regimen was first evaluated, the response rate in untreated patients was much superior to that elicited by conventional chemotherapeutic agents. We demonstrated the efficacy of PAD in relapsed or refractory patients by comparing the response rate obtained in 53 patients who received vincristine, adriamycin and dexamethasone (VAD) or equivalent regimen as induction therapy, using a comparative design in which each patient acted as their own control. Whereas 25 patients had a positive response to VAD, 37 patients had a response to PAD ≤ partial remission (PR) (p = 0.023). Using the more stringent response level of very good PR (VGPR) the results favored the PAD regimen very significantly (p = 0.006) (McNemars test). Similar results were seen using paired M-protein levels from individual patient comparisons. As the PAD regimen was subsequently adopted as the re-induction therapy in the British Society for Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X (Intensive) trial, now concluded, we have retrospectively analyzed the findings from both studies. Comparison of response rates and adverse effects of patients having had previous autologous transplantation (Cohort 1) with the corresponding data from Myeloma X showed close correlation. These findings provide evidence that rapid results may be obtained in the evaluation of newly introduced, and potentially highly effective, anti-tumour agents by direct comparison to the response to the immediately preceding standard regimen, particularly in relatively resistant tumours.

Copyright

© 2021 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - JOUR
AU  - Treen Carson Michael Morris
AU  - Mary B. Drake
AU  - Paul J. Kettle
AU  - Tracey McGuigan
AU  - Maeve Leahy
AU  - Michael O’Dwyer
AU  - Helen Enright
AU  - Tanya O’Shea
AU  - Rakesh Popat
AU  - Heather E. Oakervee
AU  - Kwee Yong
AU  - Jamie D. Cavenagh
AU  - David A. Cairns
AU  - Alberto Alvarez-Iglesias
AU  - Gordon Cook
PY  - 2021
DA  - 2021/02/08
TI  - How to Simplify the Evaluation of Newly Introduced Chemotherapeutic Interventions in Myeloma
JO  - Clinical Hematology International
SP  - 27
EP  - 33
VL  - 3
IS  - 1
SN  - 2590-0048
UR  - https://doi.org/10.2991/chi.k.210201.001
DO  - 10.2991/chi.k.210201.001
ID  - Morris2021
ER  -