Drawing First Blood
We invite two experts to debate controversial
topics in hematology and health care
Optimal Timing of Transplant in Myeloma
Shaji Kumar, MD
Ola Landgren, MD
Disclaimer:
The following positions were assigned
to the participants and do not
necessarily reflect ASH opinions, the
participants’ opinions, or what they
do in daily practice.
Agree? Disagree? We want to hear
from you! Send your thoughts and
opinions on this controversial
issue to ashclinicalnews@
hematology.org.
70
ASH Clinical News
New therapeutic options for the
treatment of multiple myeloma
are capable of achieving sustained and deep remissions,
calling into question the role of
upfront stem cell transplantation. ASH Clinical News has invited Shaji Kumar, MD, and Ola
Landgren, MD, to debate the
question: “What is the optimal
timing for hematopoietic cell
transplantation in patients with
multiple myeloma – early or delayed?” Dr. Kumar will be arguing on the “early”a side, and Dr.
Landgren will be arguing on the
“delayed” side.
Dr. Kumar is professor of medicine at Mayo Clinic College of
Medicine in Rochester, Minnesota. Dr. Landgren is professor of
medicine and chief of myeloma
service at Memorial Sloan Kettering Cancer Center in New York
City, New York.
Shaji Kumar, MD: For more than two
decades, autologous hematopoietic cell
transplantation (AHCT) has been used
for the treatment of myeloma, based on
studies that demonstrated that the combination of high-dose chemotherapy and
AHCT enhanced response rates and improved survival – particularly in younger
patients with the disease – compared with
conventional therapy alone.1
Over the past 10 to 15 years, new agents
in new therapeutic classes have become
available and have been shown to improve
patient outcomes; yet, randomized trials
have consistently demonstrated that patients
do benefit from receiving AHCT.2 I think
the majority of hematologists would agree
that AHCT is capable of producing durable
disease control and improving the survival
outcomes in multiple myeloma. Treatment
with novel drug combination can demonstrate comparable levels of response, but
complements the role of transplant.
Ola Landgren, MD: Yes, one can’t argue
that certain patients benefit from AHCT,
but does it benefit every single patient?
Every patient is unique and the myeloma
disease biology varies across patients.
Beyond these facts, the myeloma treatment landscape and our possibilities to
assess treatment response have changed
dramatically the past few years.
As you mentioned, Dr. Kumar, there
has been an influx of new drugs as alternatives to transplantation. Since 2012, when
the U.S. Food and Drug Administration
approved carfilzomib, there have been five
new agents approved either as monotherapy or as part of a multiple-drug regimen
for the treatment of multiple myeloma.
Three of these agents (elotuzumab, ixazomib, and daratumumab) were approved in
the month of November 2015 alone.
The pipeline we have ahead of us also
promises more options in the near future.
With all of these new configurations of
drugs, the response to treatment and
the duration of the response continues
to grow, raising the question of whether
the addition of high-dose melphalan will
remain the standard of care for every
patient. In simple language: Does highdose melphalan followed by AHCT add
progression-free and overall survival in
patients who already have obtained a deep
response following modern combination
therapy? This question becomes increasingly more important as the proportion
of newly diagnosed multiple myeloma pa-
tients who obtain MRD 10-6 negativity after modern effective combination therapy
already is reaching 50 to 60 percent.3
Dr. Kumar: The initial randomized trials
looking at this clinical question found that
AHCT was effective consolidation therapy
after the initial treatment of myeloma, but
these trials were conducted when available
therapies (such as doxorubicin, cyclophosphamide, vincristine, and melphalan)
were simply not as effective,1,4 and three to
four cycles of treatment failed to produce
deep responses in the vast majority of patients. If no further measures were taken,
these patients would inevitably relapse.
In these trials, AHCT served as consolidation therapy and allowed patients
to achieve much deeper responses, which
then translated into a longer relapse-free
survival and overall survival than what
was achieved in non-transplant cohorts.
Even with new, more effective therapies
for the initial treatment of myeloma,
“Transplant
should be
considered in
the context
of all available
treatment
options, not
as the default,
‘go-to’ option.”
—OLA LANDGREN, MD
recent clinical trials have shown a benefit
with transplantation, in terms of progression-free survival. The question we
now have to answer is whether transplant
should be performed early or late, after
the initial treatment has stopped working.
We will have to wait for future clinical
trials to infor m us about the advantages
and disadvantages of early versus delayed
transplant, as well as which subgroups of
patients would benefit most from transplant – either early or delayed.
February 2016