ASH Clinical News Hematology Pipeline Update: Drug Updates from the | Page 5

responses were durable, with a duration of response of 7.4 months.”
However, he added, “it should be noted that overall response
rate and duration of response, the endpoints used for the regulatory
decision, were only surrogate endpoints reasonably likely to predict
clinical benefit – hence the accelerated rather than regular approval.”
As a condition of approval, the superiority of daratumumab’s superiority over standard therapy will have to be confirmed in two ongoing
confirmatory trials.
Ixazomib
Next, Alexandria Schwarsin, MD, introduced ixazomib, the first
oral proteasome inhibitor approved for the treatment of myeloma (in
combination with lenalidomide and dexamethasone).
Ixazomib’s approval was based on results from the phase III
TOURMALINE-MM1 trial – a randomized, double-blind, placebo-controlled trial of 722 patients with relapsed/refractory myeloma who had received one to three prior therapies. The addition of
ixazomib led to longer progression-free survival (PFS) compared with
patients taking placebo plus lenalidomide and dexamethasone (20.6
months vs. 14.7 months).
“The majority of adverse actions were gastrointestinal-related,”
Dr. Schwarsin said. In terms of hematologic adverse events, grade 3/4
thrombocytopenia was higher in the ixazomib-treated arm, while
grade 3/4 neutropenia was comparable between the arms.
Hepatotoxicity was also a concern in patients treated with ixazomib. “For patients with renal impairment, a reduced dose of the
ixazomib is recommended,” Dr. Schwarsin added.
Elotuzumab
Lastly, Nicole J. Gormley, MD, reviewed the approval decision for
elotuzumab. The anti-SLAMF7 monoclonal antibody has a similar
indication to ixazomib: It is to be combined with lenalidomide and
dexamethasone for patients with relapsed/refractory myeloma.
In the pivotal trial leading to the drug’s approval, ELOQUENT-2,
median PFS, one of the study’s co-primary endpoint, was 19.4 months
when elotuzumab arm was added to lenalidomide and dexamethasone compared with 14.9 months when patients were treated with
the two-drug combination. Overall response rate, the other primary
endpoint was 78.8 percent in the elotuzumab arm, compared with
65.5 percent in the control arm.
“Respiratory and infectious adverse reactions were common,
with patients developing cough, nasal pharyngitis, upper respiratory
tract infection, and pneumonia,” Dr. Gormley noted. “Opportunistic
infections were also higher in the elotuzumab arm – primarily fungal
infections and herpes zoster.” Two patients discontinued treatment
due to hepatotoxicity, she added.
The Myeloma Specialist’s Perspective: “Continued Progress
and Real Hope”
Focusing on combination therapies and sequencing these newly
approved agents, S. Vincent Rajkumar, MD, from the Mayo Clinic
in Rochester, Minnesota, and Paul G. Richardson, MD, from the
Dana-Farber Cancer Institute in Boston, Massachusetts, then shared
their perspectives on integrating daratumumab, ixazomib, and elotuzumab in real-world practice.
To begin, Dr. Rajkumar commented on the advances in the field.

“We have witnessed
unprecedented
progress in the
treatment of multiple
myeloma, mostly
because we now have
a plethora of new
drugs to support care
pathways,” he said.
“‘Accelerated,’ ‘fast
track,’ ‘breakthrough,’
and ‘priority’ are not
just words. We in the
Barry W. Miller, MSN, CRNP
United States are fortunate that the FDA
can approve these drugs, and more importantly, that they are here to
discuss these approvals with us.”
Tracing the evolution of myeloma treatment – from melphalan to
lenalidomide plus dexamethasone to bortezomib and to the current
crop of approvals – Dr. Rajkumar highlighted the difficulties of choosing among treatments. “There are 22 potential treatment strategies
within the National Comprehensive Cancer Network guidelines,
which of course adds to the confusion,” he said.
“In myeloma, no matter what choice you make, patients will often
have to try the other and the other,” Dr. Rajkumar continued. “It’s only
a question of whether you’re making the right call on the sequence
– rather than whether you chose the wr