Clinical Hematology International (Feb 2021)

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

  • Treen Carson Michael Morris,
  • Mary B. Drake,
  • Paul J. Kettle,
  • Tracey McGuigan,
  • Maeve Leahy,
  • Michael O’Dwyer,
  • Helen Enright,
  • Tanya O’Shea,
  • Rakesh Popat,
  • Heather E. Oakervee,
  • Kwee Yong,
  • Jamie D. Cavenagh,
  • David A. Cairns,
  • Alberto Alvarez-Iglesias,
  • Gordon Cook

DOI
https://doi.org/10.2991/chi.k.210201.001
Journal volume & issue
Vol. 3, no. 1

Abstract

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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.

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