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The role of high‐dose melphalan with autologous stem‐cell transplant in multiple myeloma: is it time for a paradigm shift?
Author(s) -
Kazandjian Dickran,
Mo Clifton C.,
Landgren Ola,
Richardson Paul G.
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16764
Subject(s) - medicine , multiple myeloma , context (archaeology) , melphalan , oncology , minimal residual disease , clinical trial , autologous stem cell transplantation , tolerability , intensive care medicine , bone marrow , adverse effect , paleontology , biology
Recent advances in multiple myeloma include numerous approvals of novel therapies with unprecedented efficacy, a rapid and sustained tempo of new drug development, and further refinements to prognostication to include minimal residual disease (MRD) testing and improved risk stratification. The upfront use of immunomodulatory drug and proteasome inhibitor combinations followed by maintenance has resulted in transformative clinical benefit. Four‐drug regimens incorporating monoclonal antibodies are reporting unprecedented rates of complete response and MRD negativity in the absence of intensification. In the context of these advances, the added value of high‐dose melphalan with autologous stem‐cell transplant (HDM‐ASCT) is a key question. From a safety standpoint, HDM‐ASCT is associated with both acute toxicities that reduce quality of life and long‐term toxicities that may limit life expectancy for some patients. The present review discusses the recent advances in induction therapy, the impact of these advances on HDM‐ASCT, the evolving role of MRD testing and the short‐ and long‐term risks of HDM‐ASCT. Recognising that prospective data remains limited, we suggest that HDM‐ASCT not be considered mandatory for eligible newly diagnosed patients who are treated with highly efficacious regimens and achieve deep responses, but rather be held in reserve without early exposure to the clinical and genomic toxicity inherent to this approach.