2012-06-04
(WASHINGTON) – Results from a study published online today in Blood, the Journal of the American Society of Hematology (ASH), demonstrate that inclusion of carfilzomib, a novel targeted therapy for multiple myeloma, in combination with lenalidomide and low-dose dexamethasone, resulted in complete or near complete remission in a majority of patients with newly diagnosed multiple myeloma.
Multiple myeloma is cancer of the plasma
cells, the white blood cells in the bone marrow that normally produce
infection-fighting antibodies. Myeloma tumor cells overproduce certain
antibodies, which may damage the kidneys and other organs, weaken the normal
immune system, and also commonly cause bone destruction, leading to pain and
fractures.
Until recently, chemotherapy and steroids
were used as standard treatments for multiple myeloma. However, these traditional
therapies are not very effective at eradicating tumor cells and generally cause
high toxicities, as they destroy normal bone marrow cells along with tumor
cells. In recent years, the introduction of new drugs, such as bortezomib, lenalidomide, and thalidomide, specifically toxic to
tumor cells as compared to normal cells, has revolutionized the treatment of
multiple myeloma, increasing the depth and duration of remissions and extending
the life of myeloma patients, with limited toxicity as compared to standard
chemotherapy. An emerging agent for the treatment of multiple myeloma is carfilzomib,
a second-generation proteasome inhibitor, that has shown promising results in
clinical trials involving patients with relapsed (disease that returns after a
successful course of treatment) and/or refractory (disease that does not
respond to treatment) multiple myeloma.
“In addition to demonstrating promising
single-agent activity, a prior study investigating carfilzomib when combined with lenalidomide
and low-dose dexamethasone in relapsed multiple myeloma has shown that
the combination provides very encouraging responses with lower toxicity, as compared with standard treatment approaches,”
said Andrzej Jakubowiak, MD, PhD, the study’s
first author and Professor of Medicine at The University of Chicago School of Medicine.
“Our study aimed at investigating the agent’s efficacy and safety in newly
diagnosed multiple myeloma with this fairly novel treatment regimen.”
Led by Dr. Jakubowiak,
investigators performed a multicenter phase I/II trial involving 53
patients with newly diagnosed multiple myeloma who received a carfilzomib, lenalidomide, and low-dose dexamethasone
(CRd) regimen in 28-day cycles for up to 24 treatment cycles (initial cycles
followed by CRd maintenance) or until disease progression or intolerable
toxicity.
Study results indicate
that patients experienced a rapid and good initial response to CRd, and their
responses improved as the trial continued. Of the 49 patients who completed
four treatment cycles, 67 percent achieved at least near complete response
(nCR), with 45 percent in stringent complete response (sCR), defined as no
detectable tumor cells or myeloma protein in the blood or bone marrow. Of the 36
patients who completed eight or more treatment cycles, 78 percent achieved nCR
with 61 percent in sCR. Overall, 62 percent of trial participants had achieved
at least nCR,with 42 percent achieving sCR. The investigators also found
progression-free survival (PFS) rates were 97 percent at 12 months and 92
percent at 24 months, with all patients who achieved sCR maintaining response
for a median of nine months, demonstrating the durability of responses to this
regimen. Importantly, these periods of extended treatment were well tolerated, including
low rates of peripheral neuropathy, a treatment-limiting side effect of
bortezomib, the first-generation proteasome inhibitor.
“Our final results continue
to demonstrate the efficacy and safety of carfilzomib when combined with
lenalidomide and dexamethasone,” said Dr. Jakubowiak. “Our data support the
potential for CRd as a new frontline treatment option for patients with
multiple myeloma with results that are comparable to or better than those achieved
with other established frontline regimens followed by high-dose chemotherapy
and stem cell transplant.”
Dr. Jakubowiak and
other investigators are continuing to study this novel drug regimen in the
ongoing phase III ASPIRE trial to evaluate lenalidomide and dexamethasone with
or without carfilzomib in relapsed myeloma. The U.S. Food and Drug Administration is
currently reviewing carfilzomib for the treatment of relapsed and refractory
myeloma.
“Our hope is that our results will
provide an effective treatment option for patients with multiple myeloma to
help bring us one day closer to curing this deadly disease,” added Dr. Jakubowiak.
This manuscript was presented as an abstract at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting on June 3, 2012.
Reporters who wish to receive a copy of
the study or arrange an interview with the authors may contact Claire
Gwayi-Chore at 202-776-0544 or cgwayi-chore@hematology.org.
The American Society of Hematology is the world’s largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology. The official journal of ASH is Blood, the most cited peer-reviewed publication in the field, which is available weekly in print and online.
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