ASH Clinical News May 2015 | Page 25

CLINICAL NEWS

New highly sensitive genomic analytic
technologies allowed the researchers to
pinpoint seven specific genes that were
highly likely to be mutated in relapsed
disease, as well as how diverse those mutations were at both diagnosis and relapse.
Hopefully, the authors wrote, the methodology used in this pediatric study may
aid in developing ways to identify drugs to
target their function.
Source: Ma X, Edmonson M, Yergeau D, et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic
leukemia. Nat Comm. 2015 March 19. [Epub ahead of print]

Researchers Develop
New Potential Drug
for Rare Leukemia

A new mixed lineage leukemia– (MLL-)
menin inhibitor shows potential in
laboratory studies against acute MLL.
Jolanta Grembecka, PhD, and Tomasz
Cierpicki, PhD, from the University of
Michigan Health System, Department of
Pathology, developed the compound af-

ter identifying a small-molecule inhibitor
that would block the interaction between
the protein menin and MLL fusion proteins that cause acute MLL.
MLL represents up to 10 percent of
acute leukemias in adults and about 70
percent of acute leukemias in infants.
Current treatments are not very effective, with just over a third of patients
surviving five years. Protein-protein
interactions such as the menin-MLL
fusion protein interactions in leukemia

• Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO™ in clinical trials experienced neurological
toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including
encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and
coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients
for signs or symptoms and interrupt or discontinue BLINCYTO™ as outlined in the PI.
• Infections: Approximately 25% of patients receiving BLINCYTO™ experienced serious infections, some of which were
life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during
treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or
discontinuation of BLINCYTO™ as needed.
• Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including
pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO™ treatment.
Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO™ as needed to manage these
events.
• Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate
laboratory parameters during BLINCYTO™ infusion and interrupt BLINCYTO™ if prolonged neutropenia occurs.
• Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients
receiving BLINCYTO™ are at risk for loss of consciousness, and should be advised against driving and engaging in
hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO™ is
being administered.
• Elevated Liver Enzymes: Transient elevations in liver enzymes are associated with BLINCYTO™ treatment. The
majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or
greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment
discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to
the start of and during BLINCYTO™ treatment. BLINCYTO™ treatment should be interrupted if transaminases rise to
> 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
• Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI)
changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO™, especially in patients
previously treated with cranial irradiation and anti-leukemic chemotherapy.
• Preparation and administration errors have occurred. Follow instructions for preparation (including admixing) and
administration in the PI strictly to minimize medication errors (including underdose and overdose).

Adverse Events
• The most commonly reported adverse reactions (≥ 20%) in clinical trials were pyrexia (62%), headache (36%),
peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%)
and constipation (20%).

Dosage and Administration Guidelines
• BLINCYTO™ is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which
should be programmable, lockable, non-elastomeric, and have an alarm.
• It is very important that the instructions for preparation (including admixing) and administration provided in the full
Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see accompanying Brief Summary of Prescribing Information on adjacent pages.
R/R=relapsed/refractory; CR=complete remission; CRh*=complete remission with partial hematological recovery;
MRD=minimal residual disease

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Reference: 1. BLINCYTO™ (blinatumomab) Prescribing Information, Amgen.
BLINCYTO™ is a trademark of Amgen Inc.
© 2015 Amgen Inc. All rights reserved.
USA-103-100672 1/15

are generally considered “undruggable,”
meaning it can be particularly challenging to develop drugs that target those
interactions, the researchers explained
in their paper published in Cancer Cell.
Despite the difficulty, Dr. Grembecka
said that the MLL-menin interaction
remained tempting: “The MLL-menin
interaction is a good drug target because
it’s the primary driver in this type of
leukemia. By blocking this interaction,
it’s very likely to stop the cancer.” In the