In a recently published article, two myeloma experts discussed the
role of autologous stem cell transplantation as an initial line of
therapy in myeloma patients. The debate centered on the limited
evidence supporting stem cell transplants in the context of newer,
alternative treatment options.
An autologous stem cell transplant is a procedure in which stem
cells are collected from a patient prior to high-dose chemotherapy and
later re-infused into the body to replace the cells that were destroyed
The results of two randomized trials show that patients who
underwent stem cell transplantation had a median improved survival time
of 12 months to 18 months compared to patients who received
conventional chemotherapy. Based on these findings, stem cell
transplantation has become a standard treatment for eligible patients.
However, the role of stem cell transplantation as an initial
treatment for multiple myeloma is now in question due to the
introduction of novel and commonly used anti-myeloma agents including Revlimid (lenalidomide), thalidomide (Thalomid), and Velcade
(bortezomib). Studies have shown that most patients who receive
conventional chemotherapy along with combinations of these novel agents
demonstrate high responses within a short period of time.
According to Dr. Vincent Rajkumar of the Mayo Clinic in Rochester,
Minnesota, stem cell transplantation is one of several available
treatment options and the decision to undergo the procedure should be
based on the specific needs of the patient.
“Autologous stem cell transplantation is just one of many available
[treatment] options, and the decision on the need for stem cell
transplantation and its timing must be tailored to meet the needs of
the patient. A one-size-fits-all approach is no longer applicable in
the disease,” wrote Dr. Rajkumar.
In his opinion, the current data on the outcomes following early
stem cell transplantation are not enough to support stem cell
transplantation as a default method of initial therapy (see related Beacon news).
On the opposite side of the debate, Dr. Philippe Moreau of
University Hospital Hotel-Dieu in Nantes, France, contends that the
data currently available support the routine use of stem cell
transplantation in the treatment of eligible myeloma patients.
“Autologous stem cell transplantation is a routine procedure and is
associated with a mortality rate of less than 2 percent, which is lower
than that reported by physicians favoring continuous upfront therapy
without stem cell transplantation,” wrote Dr. Moreau.
In his opinion, future studies should concentrate on identifying the patients who would benefit most from this treatment option.
Dr. Rajkumar believes that the evidence conferring a clinical
benefit of any procedure is defined by an improvement in overall
survival or improved quality of life. Currently, there are many studies
that claim results in favor of one method over another based on
measures such as complete response or progression-free survival.
However, in Dr. Rajkumar’s opinion, these measures are not necessarily
indicative of better outcomes as far as the patient and quality of life
“As long as overall survival has not been shown to be better with
one [treatment] approach over the other, and no validate
patient-reported quality of life studies have been done, the decision
on what the appropriate timing is should be made based primarily on
patient preference, not physician preference,” wrote Dr. Rajkumar.
Dr. Brendan Weiss of the Abramson Cancer Center in Philadelphia who
was not involved in the debate, agrees with Dr. Rajkumar’s assessment
of measures relevant for outcomes.
“Complete response has not been consistently correlated with overall
survival in multiple myeloma. Until we have better biomarkers, clinical
benefit should be based on improvements in overall survival and/or
quality of life,” said Dr. Weiss.
While Dr. Rajkumar supports the use of stem cell transplantation in
clinical trials designed to find an eventual cure for myeloma, he does
not believe that the procedure should be used as a default initial
treatment for all eligible patients in a clinical setting. This is
based on his claim that there is limited work investigating the optimal
sequence of therapy involving stem cell transplantation.
According to Dr. Rajkumar, results from the few recent studies
comparing early stem cell transplantation to delayed stem cell
transplantation show no overall survival benefits that favor either
option. However, by delaying stem cell transplantation, he believes
patients can extend their time spent leading normal lives.
“A delayed stem cell transplant approach allows a person with newly
diagnosed myeloma to live the younger years of their life without
feeling like a cancer patient,” wrote Dr. Rajkumar.
Additionally, Dr. Rajkumar believes in tailoring each patient’s
course of treatment according to his or her risk factors and needs.
While he routinely supports early stem cell transplantation in
intermediate-risk patients (characterized by particular chromosomal
abnormalities), he offers standard-risk patients a choice between early
and delayed stem cell transplantation.
Dr. Moreau, on the other hand, views stem cell transplantation as a
routine, cost-effective procedure that will likely remain the standard
of care for eligible myeloma patients.
“The argument of cost does not support the use of continuous novel
agent-based therapy upfront in comparison with early stem cell
transplantation, which is less expensive than two years of therapy,” he
He notes preliminary data from a recent study that appears to favor
early stem cell transplantation over standard chemotherapy in
combination with novel agents. However, the overall survival was not
significantly different between the patient groups, and final results
have not yet been published.
While not against the idea of limiting stem cell transplantation to
a specified group of patients, Dr. Moreau asserts that the relationship
between individual risk factors and the most beneficial treatment
options have not yet been adequately identified. Thus, the best
approach would be to offer the most effective treatment for all
patients, regardless of their risk level.
“Although we are progressing towards a consensus regarding the
definition of high-risk disease, no cooperative group is currently able
to propose a risk-adapted strategy based on well-defined biological
and/or clinical characteristics,” wrote Dr. Moreau.
Dr. Weiss agrees with Dr. Moreau that risk-adapted approaches have not yet been confirmed in clinical trials.
“Unlike the case in acute leukemias, we have not performed
appropriate clinical trials to validate risk-adapted approaches, as
suggested by the Mayo Clinic. Until these studies are performed, these
biomarkers of risk are important in informing discussions of prognosis
with patients, analyzing current clinical trials, and generating
hypotheses to test in future trials,” added Dr. Weiss.
Additionally, Dr. Moreau argues that in delaying stem cell
transplantation, a patient could run the risk of not being able to
receive a transplant at all due to disease progression or additional
health complications. He references a study in which only 77 percent of
patients in a delayed stem cell transplantation group could actually
receive a transplant by the time they relapsed.
Dr. Moreau added that ongoing trials evaluating the role of stem
cell transplantation in the context of the current understanding of
myeloma will hopefully surface with results in the near future.
For more information, please see the article in Leukemia Research (abstract).
by Waldo Jaquith on Flickr – some rights reserved.