CLINICAL NEWS
On Location 2014 ASH Annual Meeting
For ASCT in Myeloma,
Does One Size Fit All?
Over the last decade, drug development for multiple myeloma has
reached an unprecedented pace, and has led to the expansion of
regimens that now include novel agents like bortezomib and lenalidomide. This rapid development has improved patient survival rates, and
there is anticipation that this trend will only continue.
At the 2014 ASH Annual Meeting, Philippe Moreau, MD, of the
University Hospital Hotel-Dieu of Nantes, France, and Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston debated
one such controversy: should all transplant-eligible myeloma patients
receive autologous stem cell treatment (ASCT)?
Dr. Moreau took the supporting position, and began by tracing the
history of ASCT to highlight the overwhelming successes of highdose melphalan/ASCT – especially when compared with conventional
chemotherapy. Combining novel agents with early stem cell treatment
has also produced favorable results, Dr. Moreau noted.
“Patients with myeloma who are given front-line stem cell transplantation are having the same mortality probability as the general
population,” he argued. “We may be able to begin to think in terms of
curing some patients with a combination of novel agents and frontline stem cell transplants.”
While recent successes in the use of novel agents alone (without
front-line stem cell transplant) have led some physicians to question
whether transplants are necessary at all, Dr. Moreau contended that
preliminary randomized data favor the role of early ASCT with novel
agents – rather than novel agents alone.
Early ASCT, he concluded, is safe (with a very low risk of mortality), highly feasible (90% feasibility vs. 69% feasibility of delayed
transplants), broadly implemented and trusted, and cost-effective
(compared to novel agents used alone).
Is ASCT Safe for All Multiple Myeloma Patients?
When Dr. Richardson took the podium, he made a point that he kept
returning to throughout his argument: “Does one size fit all?” Myeloma
is a highly heterogeneous disease that changes within the individual
patient, making “the individualization of treatment with the advent of
novel therapies the absolute priority as we go forward,” he said.
Myeloma treatment has progressed considerably, to the point that myeloma could conceivably become a chronic illness – or one that is functionally curable – Dr. Richardson said. In this context,
management of adverse events
and comorbidities becomes
extremely important.
“Does stem cell transplant
benefit every patient, and what
is its contribution to survival?”
he asked, pointing out that
the next wave of therapies will
include targeting mutations,
genetic changes, and classic
cell biology.
In that era of advanced
cellular therapies, whether
universal high-dose melphalan
combined with autologous
stem cell rescue would benefit
all myeloma patients “is something that we simply do not
know, particularly in 2014,”
Dr. Richardson said.
“Tolerability, quality of
life, relapse, and long-term
—PAUL G. RICHARDSON, MD
toxicity are key questions and
considerations that we have to
“Tolerability,
quality of life,
relapse, and
long-term
toxicity are key
questions and
considerations
that we have
to take into
account.”
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ASH Clinical News
take into account,” he continued. “At the present time we don’t know
whether stem cell transplant is needed in all MRD patients – or if there
are there features that can divide who needs what and when. Hence
participation in trials is essential.”
A Stepwise Approach to Myeloma Therapy
Following the debate, Joseph R. Mikhael, MD, MEd, of the Mayo Clinic
in Scottsdale, Arizona, offered a practical approach to help clinicians
choose a therapy in relapsed myeloma. Given the improved therapeutic
strategies discussed by Dr. Richardson and Dr. Moreau, patients are
living significantly longer with myeloma, and because of that, many
patients will require multiple lines of therapy.
Dr. Mikhael advised clinicians to employ a stepwise approach,
addressing several factors to decide on optimal treatment for each
patient. The five questions clinicians should ask themselves as part of
this approach are:
• Do I need to treat this patient now? Rapidity of relapse is important.
• Should I retreat with a previous therapy? Consider the depth and
duration of response.
• Have I employed the “Big 5” (thalidomide, bortezomib,
lenalidomide, carfilzomib, and
pomalidomide)?
• Have I used “add-on” agents?
• Have I considered an individualized, risk-stratified approach?
Using this stepwise approach, Dr. Mikhael said, can help clinicians better tailor their treatments for relapsing patients, resulting in improved
outcomes. ●
February 2015