10-K
1
gtbp_10k.htm
ANNUAL REPORT
gtbp_10k
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549 FORM 10-K
ANNUAL
REPORT PURSUANT TO SECTION 13 OR 15(d)
OF THE
SECURITIES EXCHANGE ACT OF 1934
For the
fiscal year ended December 31, 2020
Commission
File Number: 000-08092
GT BIOPHARMA, INC.
(Exact
name of Registrant as specified in its charter)
(State of incorporation or organization) (I.R.S. Employer Identification No.)
9350
Wilshire Blvd.
Suite
203
Beverly Hills, CA 90212
(Address
of principal executive offices) (Zip code)
(800) 304-9888
(Registrant’s
telephone number including area code) Securities registered
pursuant to Section 12(b) of the Act: None.
Securities
registered pursuant to section 12(g) of the Act:
Title of Securities Exchanges on which Registered
Common Stock, $.001 Par Value None
Indicate
by check mark if the registrant is a well-known seasoned issuer, as
defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate
by check mark if the registrant is not required to file reports
pursuant to Section 13 or Section 15(d) of the Act. Yes
☐ No ☒
Indicate
by check mark whether the registrant (1) has filed all reports
required to be filed by Section 13 or 15(d) of the Securities
Exchange Act of 1934 during the preceding 12 months (or for such
shorter period that the registrant was required to file such
reports), and (2) has been subject to such filing requirements for
the past 90 days. Yes ☒ No ☐
Indicate
by check mark whether the registrant has submitted electronically
and posted on its corporate website, if any, every Interactive Data
File required to be submitted and posted pursuant to Rule 405 of
Regulation S-T during the preceding 12 months (or for such shorter
period that the registrant was required to submit and post such
files). Yes ☒ No ☐
Indicate
by check mark if disclosure of delinquent filers pursuant to Item
405 of Regulation S-K (§229.405) is not contained herein, and
will not be contained, to the best of registrant’s knowledge,
in definitive proxy or information statements incorporated by
reference in Part III of this Form 10-K or any amendment to this
Form 10-K. Yes ☐ No ☒
Indicate
by check mark whether the registrant is a large accelerated filer,
an accelerated filer, a non-accelerated filer, a smaller reporting
company, or emerging growth company. See the definitions of
“large accelerated filer,” “accelerated
filer,” “smaller reporting company,” and
“emerging growth company” in Rule 12b-2 of the Exchange
Act.
Large accelerated filer ☐ Accelerated filer ☐
Emerging growth company ☐
If an
emerging growth company, indicate by check mark if the registrant
has elected not to use the extended transition period for complying
with any new or revised financial accounting standards provided
pursuant to Section 13(a) of the Exchange Act. ☐
Indicate
by check mark whether the registrant is a shell company (as defined
in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
The
aggregate market value of the registrant’s common stock,
$0.001 par value per share, held by non-affiliates on June 30, 2020
was approximately $8.9 million. As of April 12, 2021, there were
28,393,960 shares of the registrant’s common stock, $0.001
par value, issued or issuable and outstanding.
Table
of Contents
PART I 1
Item 1. Business 1
Item 1A. Risk Factors 10
Item 1B. Unresolved Staff Comments 34
Item 2. Properties 34
Item 3. Legal Proceedings 34
Item 4. Mine Safety Disclosures 34
Item 6. Selected Financial Data 36
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 43
Item 8. Financial Statements and Supplementary Data 43
Item 9A. Controls and Procedures 43
Item 9B. Other Information 44
PART III 44
Item 10. Directors, Executive Officers and Corporate Governance 44
Item 11. Executive Compensation 47
Item 14. Principal Accounting Fees and Services 54
Item 15. Exhibits, Financial Statement Schedules 55
PART I
CAUTIONARY NOTICE REGARDING FORWARD-LOOKING STATEMENTS
This
Report, including any documents which may be incorporated by
reference into this Report, contains “Forward-Looking
Statements” within the meaning of Section 27A of the
Securities Act of 1933, as amended, and Section 21E of the
Securities Exchange Act of 1934, as amended. All statements other
than statements of historical fact are “Forward-Looking
Statements” for purposes of these provisions, including our
plans of operation, any projections of revenues or other financial
items, any statements of the plans and objectives of management for
future operations, any statements concerning proposed new products
or services, any statements regarding future economic conditions or
performance, and any statements of assumptions underlying any of
the foregoing. All Forward-Looking Statements included in this
document are made as of the date hereof and are based on
information available to us as of such date. We assume no
obligation to update any Forward-Looking Statement. In some cases,
Forward-Looking Statements can be identified by the use of
terminology such as “may,” “will,”
“expects,” “plans,”
“anticipates,” “intends,”
“believes,” “estimates,”
“potential,” or “continue,” or the negative
thereof or other comparable terminology. Although we believe that
the expectations reflected in the Forward-Looking Statements
contained herein are reasonable, there can be no assurance that
such expectations or any of the Forward-Looking Statements will
prove to be correct, and actual results could differ materially
from those projected or assumed in the Forward-Looking Statements.
Future financial condition and results of operations, as well as
any Forward-Looking Statements are subject to inherent risks and
uncertainties, including any other factors referred to in our press
releases and reports filed with the Securities and Exchange
Commission. All subsequent Forward- Looking Statements attributable
to the company or persons acting on its behalf are expressly
qualified in their entirety by these cautionary statements.
Additional factors that may have a direct bearing on our operating
results are described under “Risk Factors” and
elsewhere in this report.
Introductory Comment
Throughout
this Annual Report on Form 10-K, the terms “GTBP,”
“we,” “us,” “our,” “the
company” and “our company” refer to GT Biopharma,
Inc., a Delaware corporation formerly known as DDI Pharmaceuticals,
Inc., Diagnostic Data, Inc. and Oxis International, Inc., together
with our subsidiaries.
ITEM 1. BUSINESS
We are
a clinical stage biopharmaceutical company focused on the
development and commercialization of novel immuno-oncology products
based off our proprietary Tri-specific Killer Engager
(TriKETM) fusion protein immune cell engager technology
platform. Our TriKE platform generate proprietary therapeutics
designed to harness and enhance the cancer killing abilities of a
patient’s own natural killer cells, or NK cells. Once bound
to an NK cell, our moieties are designed to enhance the NK cell,
and precisely direct it to one or more specifically-targeted
proteins expressed on a specific type of cancer cell or virus
infected cell, ultimately resulting in the targeted cell’s
death. TriKE can be designed to target any number of tumor antigens
on hematologic malignancies, sarcomas or solid tumors and do not
require patient-specific customization.
We are
using our TriKE platform with the intent to bring to market
immuno-oncology products that can treat a range of hematologic
malignancies, sarcoma and solid tumors. The platform is scalable,
and we are putting processes in place to be able to produce
IND-ready moieties in a timely manner after a specific TriKE
conceptual design. After conducting market and competitive
research, specific moieties can then be advanced into the clinic on
our own or through potential collaborations with larger companies.
We are also evaluating, in conjunction with our Scientific Advisory
Board, additional moieties designed to target different tumor
antigens. We believe our TriKE may have the ability, if approved
for marketing, to be used as a monotherapy, augment the current
monoclonal antibody therapeutics, be used in conjunction with more
traditional cancer therapy and potentially overcome certain
limitations of current chimeric antigen receptor, or CAR-T,
therapy.
We are
also using our TriKE platform to develop therapeutics useful for
the treatment of infectious disease such as for the treatment of
patients infected by the human immunodeficiency virus (HIV). While
the use of anti-retroviral drugs has substantially improved the
health and increased the longevity of individuals infected with
HIV, these drugs are designed to suppress virus replication to help
modulate progression to AIDS and to limit further transmission of
the virus. Despite the use of anti-retroviral drugs, infected
individuals retain reservoirs of latent HIV-infected cells that,
upon cessation of anti-retroviral drug therapy, can reactivate and
re-establish an active HIV infection. For a curative therapy,
destruction of these latent HIV infected cells must take place. The
HIV-TriKE contains the antigen binding fragment (Fab) from a
broadly-neutralizing antibody targeting the HIV-Env protein. The
HIV-TriKE is designed to target HIV while redirecting NK cell
killing specifically to actively replicating HIV infected cells.
The HIV-TriKE induced NK cell proliferation, and demonstrated the
ability in vitro to reactivate and kill HIV-infected T-cells. These
findings indicate a potential role for the HIV-TriKE in the
reactivation and elimination of the latently infected HIV reservoir
cells by harnessing the NK cell’s ability to mediate the
antibody-directed cellular cytotoxicity (ADCC).
Our
initial work has been conducted in collaboration with the Masonic
Cancer Center at the University of Minnesota under a program led by
Dr. Jeffrey Miller, the Deputy Director. Dr. Miller is a recognized
leader in the field of NK cell and IL-15 biology and their
therapeutic potential. We have exclusive rights to the TriKE
platform and are generating additional intellectual
prop
1
Immuno-Oncology Platform
Tri-specific Killer Engagers (TriKEs)
The
generation of chimeric antigen receptor, or CAR, expressing T cells
from monoclonal antibodies has represented an important step
forward in cancer therapy. These therapies involve the genetic
engineering of T cells to express either CARs, or T cell receptors,
or TCRs, and are designed such that the modified T cells can
recognize and destroy cancer cells. While a great deal of interest
has recently been placed upon chimeric antigen receptor T, or
CAR-T, therapy, it has certain limitations for broad potential
applicability because it can require an individual approach that is
expensive and time consuming, and may be difficult to apply on a
large scale. NK cells represent an important immunotherapeutic
target as they are involved in tumor immune-surveillance, can
mediate antibody- dependent cell-mediated cytotoxicity (ADCC),
contain pre-made granules with perforin and granzyme B and can
quickly secrete inflammatory cytokines, and unlike T cells they do
not require antigen priming and can kill cells in the absence of
major histocompatibility complex (MHC) presentation of antigens. We
believe there is a continued medical need for targeted
immuno-oncology therapies that can have the potential to be dosed
in a patient-friendly outpatient setting, can be used on a
stand-alone basis, augment the current monoclonal antibody
therapeutics or be used in conjunction with more traditional cancer
therapy. We believe our TriKE constructs have this potential and
therefore we have generated, and intend to continue to generate, a
pipeline of product candidates to be advanced into the clinic on
our own or through potential collaborations with larger
companies.
GTB-3550 TriKETM and GTB-3550 TriKETM Phase I/II Clinical
Trial
GTB-3550 is the Company's first TriKETM product candidate
which is a single-chain, tri-specific recombinant fusion protein
construct composed of the variable regions of the heavy and light
chains of anti-CD16 and anti-CD33 antibodies and a modified form of
IL-15. The GTB-3550 Phase I/II clinical trial for treatment of
patients with CD33-expressing, high risk myelodysplastic syndromes,
refractory/relapsed acute myeloid leukemia or advanced systemic
mastocytosis opened for patient enrollment September 2019. The
clinical trial is being conducted at the University of
Minnesota’s Masonic Cancer Center in Minneapolis, Minnesota
under the direction of Dr. Erica Warlick. Additional clinical trial
sites planned as we progress to the Phase II expansion part of the
clinical trial.
NK
cells represent an important immunotherapeutic target as they are
involved in tumor immune-surveillance, can mediate antibody-
dependent cell-mediated cytotoxicity (ADCC), contain pre-made
granules with perforin and granzyme B and can quickly secrete
inflammatory cytokines, and unlike T cells they do not require
antigen priming and can kill cells in the absence of major
histocompatibility complex (MHC) presentation.
Unlike
full-length antibodies, TriKE constructs are composed of a
single-chain fusion protein that binds the CD16 receptor of NK
cells directly producing a potent and lasting cytotoxic killing
response, interleukin 15 (IL-15) to promote NK cell activation,
persistence and proliferation, and a cancer cell targeting moiety.
An additional benefit TriKE may have been attractive
biodistribution, as a consequence of their smaller size, which we
expect to be important in the treatment of solid tumors. In
addition to these advantages, TriKE is designed to be
non-immunogenic, have appropriate clearance properties, and can be
engineered quickly to target a variety of tumor
antigens.
Background and Select Non-Clinical Data
In
conjunction with our research agreement with the Masonic Cancer
Center at the University of Minnesota, the exploration of targeting
NK cells to a variety of tumors initially focused on novel
bi-specific killer engagers, or BiKEs, composed of the variable
portions of antibodies targeting the CD16 activating receptor on NK
cells and CD33 (AML and MDS; see figure below), CD19/CD22 (B cell
lymphomas), or EpCAM (epithelial tumors (breast, colon, and lung))
on the tumor cells.
2
Subsequently,
a tri-specific (TriKE) construct that replaced the linker molecule
between the CD16 scFv and the CD33 scFv with a modified IL-15
molecule, containing flanking sequences, was generated and tested.
Data indicate that the CD16 x IL-15 x CD33 and CD16 x IL-15 x EpCAM
TriKEs potently induce proliferation of healthy donor NK cells,
possibly greater than that induced by exogenous IL-15, which is
absent in the BiKE platform. Targeted delivery of the IL-15 through
the TriKE also resulted in specific expansion of the NK cells
without inducing T cell expansion on post-transplant patient
samples.
When
compared to the CD16 x CD33 BiKE, the CD16 x IL-15 x CD33 TriKE is
also capable of potently restoring killing capacity of post-
transplant NK cells against CD33-expressing HL-60 Targets and
primary AML blasts. These results demonstrated the ability to
functionally incorporate an IL-5 cytokine into the BiKE platform
and also demonstrated the possibility of targeting a variety of
cytokines directly to NK cells while reducing off-target effects
and the amount of cytokines needed to obtain biologically relevant
function.
The
figure below is a schematic of a BiKE construct (top) and a TriKE
construct (bottom), which has the modified IL-15 linker between the
CD16 scFv and the CD33 scFv components.
The
TriKE constructs were also tested against three separate human
tumor cell lines: HL-60 (promyelocitic leukemia), Raji
(Burkitt’s lymphoma), and HT29 (colorectal adenocarcinoma),
in addition to a model for ovarian cancer. All cell lines contained
the Luc reporter to allow for in vivo imaging of the tumors. These
systems were used to show in vivo efficacy of BiKE (1633) and TriKE
(GTB-3550) against relevant human tumor targets (HL-60-luc) over an
extended period of time. The system consisted of initial
conditioning of mice using radiation (250-275 cGy), followed by
injection of the tumor cells (I.V. for HL-60-luc and Raji-luc,
intra-splenic for HT29-luc and IP for ovarian for MA-148-luc), a
three-day growth phase, injection of human NK cells, and repeated
injection of the drugs of interest, BiKE and TriKE (three to five
times a week). Imaging was carried out at day 7, 14, and 21, and
extended as needed.
3
Figure
A below shows the results (tumor burden and mortality) when dosing
NK cells alone (top panel), the BiKE version (lacking IL-15) of
GTB-3550 (middle panel; called 1633), and the TriKE, GTB-3550
(bottom panel; then called 161533) in the above human tumor model,
HL-60-luc. In the NK-cell-only arm, two out of the five mice were
dead by day 21 with two of the surviving mice having extensive
tumor burden as depicted by the colored images. In contrast, all
five mice in each of the BiKE and TriKE arms survived. In addition,
the tumor burden in the TriKE-treated mice was significantly less
than in the BiKE-treated mice, demonstrating the improved efficacy
from NK cells in the TriKE-treated mice.
Based
on these results, and others, the IND for GTB-3550 was filed in
June 2017 by the University of Minnesota. FDA requested that
additional preclinical toxicology be conducted prior to initiating
clinical trials. The FDA also requested some additional information
and clarifications on the manufacturing (CMC) and clinical
packages. The requested additional information and clarifications
were completed and incorporated by us into the IND in eCTD format.
We filed the IND amendment in June 2018 and announced on November
1, 2018 that we had received notification from the FDA that the IND
was open and the Company was authorized to initiate a
first-in-human Phase 1 study with GTB-3550 in AML, MDS and severe
mastocytosis. We began the Phase 1 clinical trial in September
2019.
4
Generation of humanized single-domain antibody targeting CD16 for
incorporation into the TriKE platform
To
develop second generation TriKEs, we designed a new humanized CD16
engager derived from a single-domain antibody. While scFvs consist
of a heavy and a light variable chain joined by a linker,
single-domain antibodies consist of a single variable heavy chain
capable of engaging without the need of a light chain counterpart
(see figure below).
5
These
single-domain antibodies are thought to have certain attractive
features for antibody engineering, including physical stability,
ability to bind deep grooves, and increased production yields,
amongst others. Pre-clinical studies demonstrated increased
activity (NK Cell Degranulation) and functionality (NC Cell
Cytokine Production) of the single-domain CD16 TriKE (GTB-C3550)
compared to the original TriKE (GTB-3550) (see figure below). These
data were presented at the 2017 American Society of Hematology
Conference.
Targeting Solid Tumors and Other Potentially Attractive
Characteristics
Unlike
full-length antibodies, TriKE is composed of a single-chain fusion
protein that binds the CD16 receptor of NK cells directly producing
a potentially more potent and lasting response as demonstrated by
preclinical studies. An additional benefit due to the smaller size
of TriKE is enhanced biodistribution which we expect to be
important in the treatment of solid tumors. In addition to these
potential advantages, TriKE is designed to be non-immunogenic, have
appropriate clearance properties and can be engineered quickly to
target a variety of tumor antigens. We believe these attributes
make them an ideal pharmaceutical platform for potentiated NK
cell-based immunotherapies and have the potential to overcome some
of the limitations of CAR-T therapy and other antibody
therapies.
Examples
of our earlier stage solid tumor targeting product candidates are
focused on EpCAM, Her2, Mesothelin (mesothelioma and lung
adenocarcinoma), and CD133 alone and in combination. We believe
certain of these constructs have the potential to target prostate,
breast, colon, ovarian, liver, and head and neck cancers. Depending
on the availability of drug supply, we hope to initiate human
clinical testing for certain of our solid tumor product candidates
in 2021.
Efficient Advancement of Potential Future Product Candidates
--Production and Scale Up
We are
using our TriKE platform with the intent to bring to market
multiple immuno-oncology products that can treat a range of
hematologic malignancies, sarcomas and solid tumors. The platforms
are scalable, and we are currently working with several third
parties investigating the optimal GMP production expression system
for TriKE constructs.
We
believe TriKE will have the ability, if approved for marketing, to
be used on a stand-alone basis, augment the current monoclonal
antibody therapeutics, or be used in conjunction with more
traditional cancer therapy and potentially overcome certain
limitations of current chimeric antigen receptor, or CAR-T,
therapy.
Immuno-Oncology Product Candidates
We are initially targeting certain hematologic malignancies as we
believe our product candidates may have certain advantages over
existing and other in-development products.
Our TriKE product candidates, GTB-3550 and GTB-C3550, are
single-chain, tri-specific scFv recombinant fusion proteins
composed of the variable regions of the heavy and light chains (or
heavy chain only) of anti-CD16 antibodies, wild-type or a modified
form of IL-15 and the variable regions of the heavy and light
chains of an antibody designed to precisely target a
specific tumor antigen. We
utilize the NK stimulating cytokine human IL-15 as a
crosslinker between the two scFvs which is designed to provide a
self-sustaining signal leading to the proliferation and activation
of NK cells thus enhancing their ability to kill cancer cells
mediated by antibody-dependent
cell-mediated cytotoxicity (ADCC).
6
GTB-3550
GTB-3550
is our first TriKE product candidate. It is a single-chain,
tri-specific scFv recombinant fusion protein conjugate composed of
the variable regions of the heavy and light chains of anti-CD16 and
anti-CD33 antibodies and a modified form of IL-15. We intend to
study this anti-CD16-IL-15-anti-CD33 TriKE in CD33 positive
leukemias, a marker expressed on tumor cells in acute myelogenous
leukemia, or AML, myelodysplastic syndrome, or MDS, and other
hematopoietic malignancies. CD33 is primarily a myeloid
differentiation antigen with endocytic properties broadly expressed
on AML blasts and, possibly, some leukemic stem cells. CD33 or
Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC3,
gp67, p67) is a transmembrane receptor expressed on cells of
myeloid lineage. It is usually considered myeloid-specific, but it
can also be found on some lymphoid cells. The anti-CD33 antibody
fragment that will be used for these studies was derived from the
M195 humanized anti-CD33 scFV and has been used in multiple human
clinical studies. It has been exploited as target for therapeutic
antibodies for many years. We believe the recent approval of the
antibody-drug conjugate gemtuzumab validates this targeted
approach.
About High-Risk
Myelodysplastic Syndromes
MDS is
a rare form of bone marrow-related cancer caused by irregular blood
cell production within the bone marrow. As a result of this
irregular production, MDS patients do not have sufficient normal
red blood cells, white blood cells and/or platelets in circulation.
High-risk MDS is associated with poor prognosis, diminished quality
of life, and a higher chance of transformation to acute myeloid
leukemia. Approximately 40% of patients with High-Risk MDS
transform to AML, another aggressive cancer with poor
outcomes.
About Acute Myeloid Leukemia
Acute
myeloid leukemia is a type of cancer in which the bone marrow makes
abnormal myeloblasts (a type of white blood cell), red blood cells,
or platelets. According to the National Cancer Institute (NCI), the
five-year survival rate is about 35% in people under 60 years old,
and 10% in people over 60 years old. Older people whose health is
too poor for intensive chemotherapy have a typical survival of five
to ten months. AML accounts for roughly 1.8% of cancer deaths in
the United States.
About GTB-3550 TriKETM Clinical Trial
We
opened our GTB-3550 Phase I/II clinical trial in September 2019,
and enrolled our first patient in January 2020. Patients with CD33+
malignancies (primary induction failure or relapsed AML with
failure of one reinduction attempt or high-risk MDS progressed on
two lines of therapy) age 18 and older are eligible
(ClinicalTrials.gov Identifier NCT03214666). The primary endpoint is to
identify the maximum tolerated dose (MTD) of GTB-3550 TriKETM.
Correlative objectives include the number, phenotype, activation
status and function of NK cells and T cells.
Our Strategy
Our
goal is to be a leader in immuno-oncology therapies targeting a
broad range of indications including hematological malignancies,
sarcoma and solid tumors. Key elements of our strategy are
to:
Rapidly advanced our Tri-specific Killer Engagers (TriKEs),
GTB-3550 and GTB-C3550
Our
TriKE product candidates have the potential to be groundbreaking
therapies targeting a broad range of hematologic malignancies,
sarcomas and solid tumors. We are preparing to study GTB-3550, an
anti-CD16-IL-15-anti-CD33 TriKE in CD33 positive leukemias, a
marker expressed on tumor cells in AML, MDS and other myeloid
malignancies. We began a Phase 1 clinical trial in September 2019
and enrolled our first patient in January 2020 for patients with
relapsed/refractory AML. The Phase 1 trial will be a dose finding
study. We expect this will be closely followed by Phase 2 trials to
determine the most efficacious dosing and cycles with the aim to
maximize efficacy while minimizing on-target, off-disease adverse
events.
7
GTB-C3550
is a next-generation, follow-on, to our lead TriKE, GTB-3550.
GTB-3550 studies will help inform the development of GTB-C3550. We
believe this will de-risk the GTB-C3550 program as the data being
generated will help to make informed decisions on which, or both,
will be brought into later phase studies and in which patient
populations.
Utilize our TriKE platform technologies to develop a robust
pipeline of targeted immuno-oncology products targeting a wide
range of hematologic malignancies, sarcomas and solid tumors for
development on our own and through potential collaborations with
larger pharmaceutical companies
We are
using our TriKE platform with the intent to bring to market
multiple, targeted, off-the-shelf therapies that can treat a range
of hematologic malignancies, sarcomas and solid tumors. The
platforms are scalable and we are currently working with several
third parties investigating the optimal expression system of the
TriKE constructs which we expect to be part of a process in which
we are able to produce IND-ready moieties in approximately 90-120
days after the construct conceptual design. After conducting market
and competitive research, specific moieties can then be rapidly
advanced into the clinic on our own or through potential
collaborations with larger pharmaceutical companies.
We
believe our TriKE will have the ability, if approved for marketing,
to be used on a stand-alone basis, augment the current monoclonal
antibody therapeutics, or be used in conjunction with more
traditional cancer therapy and potentially overcome certain
limitations of current chimeric antigen receptor, or CAR-T,
therapy.
Oncology Markets
B-cell Lymphomas/Leukemias
B-cell
lymphoma is a type of cancer that forms in B cells (a type of
immune system cell). B-cell lymphomas may be either indolent (slow-
growing) or aggressive (fast-growing). Non- Hodgkin lymphoma has an
incidence rate of 19.4 per 100,000 per year and B-cell lymphomas
make up most (about 85%) of NHL in the United States. There are
many different types of B-cell non- Hodgkin lymphomas. These
include Burkitt lymphoma, chronic lymphocytic leukemia/small
lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma,
follicular lymphoma, and mantle cell lymphoma.
Acute Lymphoblastic Leukemia
Acute
lymphoblastic leukemia, or ALL, is an acute form of leukemia, or
cancer of the white blood cells, characterized by the
overproduction and accumulation of immature white blood cells,
known as lymphoblasts. In persons with ALL, lymphoblasts are
overproduced in the bone marrow and continuously multiply, causing
damage and death by inhibiting the production of normal cells (such
as red and white blood cells and platelets) in the bone marrow and
by spreading (infiltrating) to other organs.
"Acute"
is defined by the World Health Organization standards, in which
greater than 20% of the cells in the bone marrow are blasts.
Chronic lymphocytic leukemia is defined as having less than 20%
blasts in the bone marrow. Acute lymphoblastic leukemia is seen in
both children and adults; the highest incidence is seen between
ages 2 to 3 years (>90 cases per 1 million per year). ALL is the
most common cancer diagnosed in children and represents
approximately 25% of cancer diagnoses among children younger than
15 years. Among children with ALL, approximately 98% attain
remission, and approximately 85% of patients aged 1 to 18 years
with newly diagnosed ALL treated on current regimens are expected
to be long-term event-free survivors, with over 90% surviving at 5
years.
Myeloid Leukemias
Acute Myeloid Leukemia
AML is
a heterogeneous hematologic stem cell malignancy in adults with
incidence rate of 4.3% per 100,000 populations. The median age at
the time of diagnosis is 68 years. AML is an aggressive disease and
is fatal without anti-leukemic treatment. AML is the most common
form of adult leukemia in the U.S. These patients will require
frontline therapy, usually chemotherapy including cytarabine and an
anthracycline, a therapy that has not changed in over 40 years.
Myelodysplastic syndromes (MDS) are a heterogeneous group of