Targeted Blood Cancer Therapies Offer Significant Improvements in Survival, Increased Options for Patients
Published on: December 06, 2015
(ORLANDO, December 6,
2015) – New, highly targeted treatment approaches for leukemia, lymphoma, and
myeloma to be presented today at the 57th American Society of Hematology (ASH)
Annual Meeting and Exposition represent a tremendous expansion of oral and
intravenous therapy options for patients with blood cancers.
landscape for hematologic malignancies is evolving rapidly, as recent insights
into the genetic signatures of disease continue to inform the development of
targeted therapies and identify new uses for those that are already approved. These
potent therapies are more effective and potentially safer than standard
chemotherapy because they target specific proteins and mutated gene products while
leaving other cells unharmed. While these treatments illustrate the exciting
progress that researchers have made in the last several years, more options are
needed to further improve outcomes for patients.
Studies to be
presented today not only illustrate immense progress in the treatment of blood
cancers, but they also represent a future of cancer research that is
genetically driven and increasingly personalized.
- One presentation will share the results of a promising
experimental treatment for acute myeloid leukemia (AML) that targets a specific
genetic mutation – the first genetically driven study for a disease for which
no new drugs in use have been approved since 1990.
- Another study takes the opposite approach; instead of
developing a therapy that hones in on a new target, investigators re-purpose
rituximab, a therapy already used to treat a range of cancers of the immune
system, to treat B-cell precursor acute lymphocytic leukemia (BCP-ALL), a rare type
of leukemia, to improve outcomes in adults who typically respond poorly to
studies aimed to identify improved options for patients with relapsed or
treatment-resistant multiple myeloma (MM), a cancer of the plasma cells. The
two therapies to be presented today, ixazomib and daratumumab, received
approval from the United States Food and Drug Administration in November 2015
based on new data.
- One study demonstrates significantly improved response
rates by adding ixazomib to standard treatment for patients with relapsed and
treatment-resistant multiple myeloma.
- The second MM study offers an entirely new approach to
treating this disease with daratumumab, a targeted therapy that represents a
significant improvement over the current options for patients.
three studies report impressive outcomes with new therapies for patients with
chronic lymphocytic leukemia (CLL), a blood cancer that occurs when abnormal
white blood cells called lymphocytes accumulate in the blood, bone marrow, and
lymph nodes or other organs, causing these organs to enlarge. Nearly 70 percent
of people affected by CLL are 65 or older:
- A study of ibrutinib, an oral therapy that targets
B-cell malignancies, in patients with previously untreated CLL/small
lymphocytic lymphoma underscores the promise of targeted therapy for elderly
- A late-breaking study, unblinded early because of
“outstanding efficacy,” demonstrates that combining orally administered
idelalisib with standard treatment for relapsed or treatment-resistant CLL dramatically
increases patient survival without disease progression.
- An additional late-breaking study of a high-risk group
of CLL patients suggests that venetoclax, an experimental oral therapy improves
response rates in a way that has not been seen before in this particular
today showcase dramatic advances that are revolutionizing the way we treat
patients with blood cancers, as well as the promise of novel approaches yet to
come,” said Gary Schiller, MD, Professor of Medicine in the Division of
Hematology/Oncology at the University of California, Los Angeles School of
Medicine. “We are seeing how scientific discoveries in the lab are translating
into real, positive clinical impact. Patients, especially those with challenging
diseases, can be heartened by the tremendous expansion of options and new therapeutic
This press conference will take place on Sunday, December 6, 2015, at 11:00
a.m. in Room W208AB of the Orange County Convention Center.
Targeted Therapy for Genetically Defined Subset of Patients with Acute Myeloid
Leukemia Significantly Improves Survival
The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared
with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction
(ind), High-Dose C Consolidation (consol), and as Maintenance (maint) Therapy
in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with
FLT3 Mutations (muts): An International Prospective Randomized (rand)
P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance])
- Acute myeloid leukemia (AML) is one of the most common
forms of adult leukemia. Most of the approximately 30 percent of AML patients
whose leukemia cells have a mutation in the FLT3 gene have a
particularly poor prognosis, as their disease tends to be more aggressive and
is associated with a higher incidence of relapse. While targeted therapies have
improved treatment for other blood cancers, there have been few advances in
- Midostaurin is an
experimental drug that inhibits many enzymes, including mutant FLT3.
- This Phase III, multinational, randomized trial analyzed
whether adding midostaurin to standard chemotherapy would improve survival when
compared to standard chemotherapy alone in adults aged 18 to 60 with this
- Investigators randomized 717 adult patients with
FLT3-mutated AML to receive either midostaurin (360) in pill form or placebo
(357) in addition to standard chemotherapy followed by one year of maintenance therapy
with the new drug.
- The median time to either failure to achieve
remission, relapse, or death in patients who received midostaurin was eight
months compared to only three months in the standard treatment arm.
- Standard chemotherapy with midostaurin and one year of
maintenance therapy significantly improved median overall survival (74.7 months
compared to 26.0 in the group receiving only standard therapy).
- These findings suggest that midostaurin improves
outcomes in younger adults with AML with this mutation when added to the
standard chemotherapy regimen.
M. Stone, MD, Dana-Farber Cancer Institute, Boston, will present this study
during the Plenary Scientific Session on Sunday, December 6, at 2:00 p.m. in
Hall D, level 2 of the Orange County Convention Center.
Finds New Use for Rituximab in Acute Leukemia
Addition of Rituximab Improves the Outcome of Adult Patients with
CD20-Positive, Ph-Negative, B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL):
Results of the Randomized Graall-R 2005 Study 
- Rituximab is a synthetic molecule engineered to target
the protein CD20, which is found on the surface of many blood cancer cells. This
therapy is already approved for treating patients with other malignancies,
including B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia.
- CD20 is present in 30 to 50 percent of patients with B-cell
precursor acute lymphocytic leukemia (BCP-ALL), a type of leukemia that is
common in children but also affects adults. Results of standard therapy in
adults is poor compared to results achieved in children.
- This multicenter, randomized clinical trial aimed to
evaluate the benefit of adding rituximab to standard chemotherapy for patients
aged 18 to 59 with newly diagnosed CD20-positive Philadelphia
- Investigators randomized 220 patients to receive
chemotherapy with or without rituximab for a total of 16 to 18 infusions.
- After a median follow up of 30 months, patients who
received rituximab had a lower incidence of relapse compared to those who did
not (18% in the rituximab arm vs. 30.5% in the control arm). Furthermore, 65
percent of patients in the rituximab arm achieved two-year event-free survival
compared to 52 percent of those who did not receive the drug.
- The study suggests that adding rituximab to standard
therapy improves event-free survival for patients with BCP-ALL.
Maury, MD, Hôpital Henri Mondor, Créteil, France, will present this study
during the Plenary Scientific Session on Sunday, December 6, at 2:00 p.m. in
Hall D, level 2 of the Orange County Convention Center.
Presents Exciting Evidence for First All-Oral Treatment for Relapsed and Treatment-Resistant
Ixazomib, an Investigational Oral Proteasome Inhibitor (PI), in
Combination with Lenalidomide and Dexamethasone (IRd), Significantly Extends
Progression-Free Survival (PFS) for Patients (Pts) with Relapsed and/or Refractory
Multiple Myeloma (RRMM): The Phase III Tourmaline-MM1 Study (NCT01564537)
- One of the current global standards of care for
patients with relapsed or treatment-resistant multiple myeloma is a combination
of the drug lenalidomide and the steroid dexamethasone. Both of these drugs can
be taken in pill form.
- Often a class of drug called proteasome inhibitors can
be used in combination with dexamethasone or added to lenalidomide and
dexamethasone to improve treatment for relapsed or treatment-resistant multiple
myeloma. Until now, proteasome inhibitors have only been available for use intravenously
or subcutaneously. Ixazomib is the first of these drugs to be available in pill
form. In this Phase III study, 722 patients with relapsed or
treatment-resistant multiple myeloma were randomized to receive either the
standard treatment regimen of lenalidomide and dexamethasone or a combination of
the standard treatment with weekly doses of ixazomib. The median age of
patients participating in the trial was 66.
- Patients repeated treatment cycles until their disease
progressed or side effects became intolerable.
- At the first interim analysis, the patients who
received ixazomib lived a median of 20.6 months without their disease
progressing. Patients who received placebo instead of ixazomib demonstrated
progression-free survival of 14.7 months.
- Toxicity was similar among both treatment groups, as
68 percent of patients in the ixazomib arm suffered severe but not
life-threatening adverse events compared to 61 percent of patients in the
- The study suggests that adding ixazomib to standard
treatment for relapsed or treatment-resistant multiple myeloma increases time
before disease progression. Notably, ixazomib plus lenalidomide and
dexamethasone represents the first all-oral combination treatment for multiple
Moreau, MD, University of Nantes, Nantes, France, will present this study
during an oral presentation on Monday, December 7, at 2:45 p.m. EST in room
Tangerine 2 (WF2), level 2 of the Orange County Convention Center.
Targeted Therapy for Multiple Myeloma Effective Against Hard-to-Treat Disease
Daratumumab in Combination with Lenalidomide and Dexamethasone in
Patients with Relapsed or Relapsed and Refractory Multiple Myeloma (RRMM):
Updated Results of a Phase I/II Study (GEN503) 
- Myeloma is cancer of the plasma cells, white blood
cells that produce infection-fighting antibodies.
- Daratumumab, the first targeted antibody therapy for
multiple myeloma, is an experimental agent that is part of a new class of drugs
called anti-CD38 antibodies. These drugs first bind to the CD38 protein
expressed on the surface of myeloma cells and then signal immune cells to kill
the cell directly.
- In this Phase I/II study of daratumumab in combination
with standard multiple myeloma therapy, lenalidomide and dexamethasone,
researchers sought to evaluate whether this treatment combination is safe and
effective for patients with relapsed or treatment-resistant multiple myeloma.
- Thirty-two patients received weekly doses of
daratumumab in combination with standard therapy during the first two 28-day
therapy cycles and then biweekly infusions during the next four cycles followed
by once monthly infusions. Patients received the treatment until their disease
progressed or side effects became too severe to continue.
- As of October 2, 2015, 22 patients remained on
treatment. Ten (3%) discontinued treatment due to disease progression, adverse
events, or investigator decision. The overall response rate was 81 percent and
63 percent had a very good partial response or better.
- The median duration of response was not reached.
- Results of the study suggest that daratumumab is a
safe and effective treatment for patients with relapsed or treatment-resistant
Plesner, MD, of Vejle Hospital, University of Southern Denmark, Vejle, Denmark,
will present this study during an oral presentation on Monday, December 7, at 7:30
a.m. in Hall E1, level 2 of the Orange County Convention Center.
Underscores Promise of Targeted Therapies as First-line Approach for Patients
with Chronic Lymphocytic Leukemia
Results from the International, Randomized Phase III Study of Ibrutinib
Versus Chlorambucil in Patients 65 Years and Older with Treatment-Naïve CLL/SLL
(RESONATE TM-2) 
- Chronic lymphocytic leukemia/small lymphocytic
lymphoma (CLL/SLL) primarily affects older patients who often have other
chronic diseases or conditions. In this
population of patients, chlorambucil has been a standard first-line therapy.
- This randomized, Phase III study sought to evaluate
the efficacy and safety of ibrutinib, a first-in-class, oral, Bruton’s tyrosine
kinase inhibitor that targets B-cell malignancies in newly diagnosed,
previously untreated older patients with CLL/SLL.
- Investigators randomized 269 patients with a median
age of 73 years to receive either continuous daily doses of ibrutinib or the
chemotherapy drug chlorambucil for up to 12 treatment cycles.
- Based on investigator assessment, patients who received
ibrutinib achieved an eighteen-month progression-free survival rate of 93.9
percent versus 44.8 percent in patients treated with chlorambucil.
- In addition, patients who received ibrutinib achieved a
twenty-four-month overall survival rate of 97.8 percent versus 85.3 percent in
patients treated with chlorambucil.
- The results underscore that targeted therapy is
effective in patients with previously untreated CLL/SLL and suggest that
ibrutinib should be the standard of care for this population.
Tedeschi, MD, of Azienda Ospedaliera Niguarda Cà Granda Milano Italy, will
present this study during an oral presentation on Monday, December 7, at 7:30
a.m. in room Valencia A (W415A), level 4 of the Orange County Convention
Therapy with Idelalisib Better Prevents Disease Progression in Relapsed or
Treatment-Resistant Chronic Lymphocytic Leukemia than Current Regimen
Plus Bendamustine and Rituximab (BR) is Superior to BR Alone in Patients with
Relapsed/Refractory Chronic Lymphocytic Leukemia: Results of a Phase III
Randomized Double-Blind Placebo-Controlled Study [LBA-5]
is a targeted therapy which is approved in combination with rituximab for
the treatment of patients with relapsed chronic lymphocytic leukemia
(CLL). This highly selective compound targets the delta isoform of the PI3
kinase enzyme, which is critical for the activation and survival of CLL
cells and other low-grade B-cell lymphomas.
conducted a Phase III, randomized, placebo-controlled study that evaluated
the efficacy of idelalisib when added to bendamustine and rituximab (BR),
the standard treatment regimen for patients with relapsed or treatment-resistant
total of 416 patients were enrolled. Of those, 207 received 150 mg of
idelalisib twice daily plus BR, and 209 received placebo plus BR. Patients
received six cycles of therapy until their disease progressed or they
experienced unacceptable toxicity.
pre-specified interim analysis revealed that median progression-free
survival, the primary endpoint, was 23 months in the idelalisib arm
compared to 11 months in the placebo arm. Based on this result, the
Independent Data Monitoring Committee recommended the study be unblinded
based on “overwhelming efficacy.”
addition, there was a statistically significant improvement in overall
survival, a secondary endpoint, for patients treated on the idelalisib plus
BR arm compared to the BR plus placebo arm.
safety profile of idelalisib plus BR was consistent with prior reported
studies. The most common severe adverse events were related to low white
blood cell count and anemia.
study suggests that idelalisib in combination with BR provides better
outcomes for patients than BR alone, reducing the risk of both disease
progression and death with a tolerable safety provide. This combination is
an important new option for patients with relapsed or treatment-resistant
Andrew D. Zelenetz, MD, PhD, Memorial Sloan
Kettering Cancer Center, New York, will present this study during the
Late-Breaking Abstracts Session on Tuesday, December 8, at 7:30 a.m. in Hall D,
level 2 of the Orange County Convention Center.
Oral Therapy for Ultra High-Risk Chronic Lymphocytic Leukemia Shows Promise
(ABT-199/GDC-0199) Monotherapy Induces Deep Remissions, Including Complete
Remission and Undetectable MRD, in Ultra-High Risk Relapsed/Refractory Chronic
Lymphocytic Leukemia with 17p Deletion: Results of the Pivotal International
Phase II Study [LBA-6]
- Patients with chronic lymphocytic leukemia (CLL) harboring
17p deletion have a particularly poor prognosis and limited treatment options.
- Venetoclax is an oral, targeted drug that inhibits BCL-2,
a protein that regulates natural cell death. BCL-2 is over-expressed in CLL,
leading to the accumulation of leukemia cells.
- In a previous Phase I study, venetoclax demonstrated a
77 percent overall response rate for patients with relapsed or treatment-resistant
- A pivotal Phase II trial was conducted to assess
efficacy in CLL patients with 17p deletion. A total of 107 patients with
relapsed or treatment-resistant disease took venetoclax once daily with a
weekly dose ramp-up schedule. Patients remained on daily 400 mg until disease
progression or discontinuation for another reason.
- The primary endpoint was overall response rate as
assessed by an independent committee. Efficacy was examined once patients had
completed 36 weeks of venetoclax, experienced disease progression, or
discontinued the trial.
- The overall response rate was 79.4 percent. Of all
responders, 84.7 percent maintained their response at 12 months.
- More than 20 percent of responders had undetectable leukemia
cells after therapy.
- More than 10 percent of patients achieved “deep
responses” (i.e., no detectable disease or only minimal nodules remaining in
the bone marrow), a predictor of long-term remission which has not been
previously reported in this population.
- Toxicity was acceptable in this extremely high-risk
patient population. Among 11 deaths, seven were due to progressive disease, and
four due to adverse events.
- Results suggest that venetoclax is a promising option
for this very difficult-to-treat CLL patient population characterized by 17p
Stilgenbauer, MD, University of Ulm, Germany, will present this study during
the Late-Breaking Abstracts Session on Tuesday, December 8, at 7:30 a.m. in
Hall D, level 2 of the Orange County Convention Center.
Society of Hematology 57th Annual Meeting
The study authors and
press program moderator will be available for interviews after the press
conference or by telephone. Additional press briefings will take place
throughout the meeting on gene therapy, precision medicine, supportive care for
patients with blood diseases, and sickle cell disease. For the complete annual
meeting program and abstracts, visit www.hematology.org/annual-meeting. Follow @ASH_hematology and #ASH15 on Twitter and like ASH on Facebook for the most up-to-date
information about the 2015 ASH Annual Meeting.
The American Society
of Hematology (ASH) (www.hematology.org) is the world's largest
professional society of hematologists dedicated to furthering the
understanding, diagnosis, treatment, and prevention of disorders affecting the
blood. For more than 50 years, the Society has led the development of
hematology as a discipline by promoting research, patient care, education,
training, and advocacy in hematology. The official journal of ASH is Blood (www.bloodjournal.org), the most cited peer-reviewed
publication in the field, which is available weekly in print and online and has
been serving the hematology community for 70 years.
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