ASH News Daily 2017 - Issue 3 - A-2

ASH News Daily

Page A-2

Monday, December 11, 2017

P L E N A RY - S YS T E M I C M A S T O C Y T O S I S

ASH News Daily
2017 Editorial Board
Editor

Saad Zafar
Usmani, MD,
FACP,
Levine Cancer
Institute,
Charlotte, NC
@szusmani
Authors

Farrukh
Awan, MD,
The Ohio
State
University,
Columbus,
OH
@awandoc
Mehdi
Hamadani,
MD, Medical
College of
Wisconsin,
Milwaukee, WI
@medihumandani
Lynn
Lederman,
PhD,
Mamaroneck,
NY
@lynnelederman

Mastocytosis Leading the Way
By Farrukh Awan, MD

n a hot and humid summer
day some years ago, I saw
a patient in my clinic who
presented with a history of anaphylactic shock. Unfortunately for him,
the first episode of anaphylaxis happened when he was exposed to the
interior of his recently acquired vintage 1969 Chevy Camaro. Presumably he was allergic to the leather
as we later discovered. Luckily, he
received timely intervention from
the emergency medical responders. While in the hospital he was
found to have anemia, thrombocytopenia, urticaria pigmentosa, and
an elevated serum tryptase level.
Further workup including a bone
marrow biopsy established a diagnosis of aggressive systemic mastocytosis with the presence of KIT
D816V mutation. Despite multiple
aggressive chemotherapeutic regimens his disease failed to respond.
He started treatment on a clinical
trial of a new drug called PKC412;
the rest as they say is history. He
responded very nicely to treatment
and had complete resolution of

Dr. Daniel J. DeAngelo

his symptoms and normalized his
counts. He was also able to enjoy
his vintage car before he died three
years later of unrelated causes.
These results with midostaurin or
PKC412 for an extremely uncommon disease, advanced systemic
mastocytosis (overall response rate
of 60% and median progression free
survival in excess of 1 year) with a
generally poor prognosis, were remarkable enough to merit publica-

tion in The New England Journal of
Medicine and led to the approval of
the drug for this indication.
Midostaurin is a multikinase
inhibitor that also targets KIT harboring the D816V mutation, which
is key driver mutation in approximately 90 percent of patients with
the spectrum of mast cell disorders
that include aggressive systemic
mastocytosis (ASM), SM with an
associated hematologic neoplasm
(SM-AHN), and mast cell leukemia
(MCL). The promising results with
this agent led to the development of
a more specific KIT inhibitor BLU285. In the Plenary Scientific Session presentation titled "Clinical
Activity in a Phase I Study of Blu285, a Potent, Highly-Selective Inhibitor of KIT D816V in Advanced
Systemic Mastocytosis (AdvSM),"
Dr. Daniel J. DeAngelo of DanaFarber Cancer Institute presented
exciting phase I results of the highly
potent and KIT-specific, once daily
oral inhibitor from patients with
ASM or relapsed and refractory
myeloid malignancies. In addition
»» ASM Page A-27

P L E N A RY - LY M P H O M A

Hugh Young
Rienhoff, MD,
MyDaughters
DNA.org,
Imago
BioSciences,
San Carlos, CA
Nina Shah,
MD,
University
of California,
San Francisco,
CA
@ninashah33
Binod Dhakal, MD, MS, Medical College of Wisconsin; and
Peter Forsberg, MD, University of Colorado, are serving
as a Junior Authors this year.
©2017 by the American Society of
Hematology
All materials contained in this
newspaper are protected by
copyright laws and may not be
used, reproduced, or otherwise
exploited in any manner without
the expressed prior permission of
ASH News Daily.
Contributing authors have declared
any financial interest in a product
or in potentially competing
products, regardless of the dollar
amount. Any such financial interest
is noted with the respective articles.

Brentuximab Rises to the
Top Echelon of Hodgkin Therapeutics
By Mehdi Hamadani, MD

s this trial absolutely the best option for my patient?" I intensely
debated this question in my
mind, as I systematically discussed
the pros and cons of the ECHELON-1 trial (a randomized study of
ABVD vs. brentuximab vedotin [BV]
+ AVD) with a starry-eyed, quietly
confident, second-year medical student with newly diagnosed Hodgkin lymphoma (HL) in my clinic,
flanked by her loving but understandably terrified parents. "What
if she develops severe neuropathy?
Will that jeopardize her residency
training options down the line?"
and other similar questions raced
through my mind. Several months
down the road, development of crippling motor neuropathy in a middleaged male patient randomized to BV
+ AVD arm of the same trial in my
clinic made me pause and question if
this trial will change the standard of
care in HL. These toxicity concerns
undoubtedly pale in comparison
to Drs. Vincent DeVita and George
Canellos' heroic efforts in developing MOPP (mustargen, oncovin,
procarbazine, prednisone) in the
1960s as the first combination che-

Dr. Joseph Connors

motherapy shown to cure advanced
HL. Answers to some of these important questions were presented in
the form of the penultimate Plenary
Scientific Session presentation at the
2017 ASH annual meeting.
Echelon-1 was an open-label,
randomized, multicenter, phase III
study comparing ABVD with BV +
AVD as frontline therapy in 1,334
previously untreated advancedstage HL patients. The presenting
author Dr. Joseph Connors of British Columbia Cancer Agency reported that the primary endpoint of
Echelon-1 of modified progression-

free survival (PFS; defined as time
to progression, death, or evidence
of incomplete response followed
by subsequent anticancer therapy)
was met both by independent review facility assessment (HR, 0.77;
95% CI, 0.60-0.98; p=0.03), as well
as by investigator assessment (HR,
0.72; 95% CI, 0.57-0.92; p=0.007).
There were 28 deaths in the BV +
AVD arm and 39 in the ABVD arm
(interim overall survival HR, 0.72;
95% CI, 0.44-1.17; p=0.19). Complete remission (CR) rate at the
end of frontline therapy, the rate of
PET negativity at the end of cycle
2, duration of response, duration
of CR, and event-free survival, also
trended in favor of A+AVD. Certain
subgroups seemed to benefit more
with BV + AVD including North
American patients, patients with
more than one extranodal site of
involvement, patients with highrisk disease (i.e., an International
Prognostic Score of 4 to 7), men,
and younger patients (<60 years).
Both neutropenia and febrile neutropenia were more common with
the addition of BV. However, in a
smaller subgroup of patients who
»» LYMPHOMA Page A-27

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 3