The document outlines the classification and characteristics of non-Hodgkin lymphomas (NHL), emphasizing their heterogeneous nature derived from various immune cells and providing statistics on incidence and types. Diffuse large B-cell lymphoma (DLBCL) is highlighted, along with its potential causes, developmental origins, and emerging treatment modalities like CAR T-cell therapy. The document also discusses treatment-related toxicities, particularly cytokine release syndrome and the FDA-approved CAR T therapies for specific lymphoma types.

1. B CELL
LYMPHOMAS
>CLASSIFICATION>D L B C L
Dr. Umair
Afzal
FCPS Medical Oncology
Resident
INMOL Lahore

3. CLASSIFICATION
Rappaport et al 1956
Kiel classification
International Working Formulation (IWF)
Classification
Revised European American Classification
(REAL)
World Health Organization (WHO)
Classification 2001

4. The current approach is based on the
integration of morphologic, phenotypic,
genetic, and clinical features that allows the
identification of distinct disease entities

6. NON-HODGKIN LYMPHOMAS (NHLS) ARE
A HETEROGENEOUS GROUP OF
MALIGNANCIES DERIVED FROM MATURE
B, T, AND NK CELLS, ENCOMPASSING
SEVERAL BROAD CATEGORIES AND
NEARLY 100 UNIQUE BIOLOGIC
SUBTYPES.
NHL is the sixth most common cause of cancer in
men, and the seventh most common cause in women.
In 2017, there have been approximately 80,000 new
cases of NHL and 22,000 deaths.

7. FL = 20 %
DLBCL = 36
%
CLL/SLL = 15
%

8. CLINICIANS GROUP NHL
SUBTYPES INTO
Indolent
Aggressive
Highly aggressive
To facilitate clinical decision making regarding therapy
and to estimate disease behavior.

11. D L B C L
DIFFUSE LARGE B CELL
LYMPHOMA

12. ETIOLOGY
Mostly Unknown.
Innate or acquired immunodeficiency,
Environmental exposures
Familial predisposition
Lymphotropic organisms

15. PATHOPHYSIOLOGY, B-CELL
NHL (B-NHL) DEVELOPS AT
VARIOUS POINTS DURING
NORMAL B-CELL ONTOGENY
(ORIGIN AND DEVELOPMENT).
THE MAJORITY OF B-CELL
LYMPHOMAS ARE THOUGHT TO
ORIGINATE IN THE GERMINAL
CENTER.

26. TREATMENT

43. CHIMERIC ANTIGEN
RECEPTOR T-CELL THERAPY
CART
A rapidly emerging immunotherapy approach is called adoptive cell
transfer (ACT): collecting and using patients’ own immune cells to
treat their cancer. There are several types of ACT , but, thus far, the
one that has advanced the furthest in clinical development is called
CAR T-cell therapy.

44. Chimeric antigen receptors (CARs, also known as chimeric
immunoreceptors, chimeric T cell receptors or artificial T cell
receptors) are engineered receptors that combine a new specificity
with an immune cell to target cancer cells. Typically, these receptors
graft the specificity of a monoclonal antibody onto a T cell. The
receptors are called chimeric because they are fused of parts from
different sources. CAR-T cell therapy refers to a treatment that uses
such transformed cells for cancer therapy.

45. CAR-T cells are developed to be specific to an antigen expressed on a
tumor that is not expressed on healthy cells. CD19 is expressed on
B-cells throughout their development and as a result, CD19 is also
expressed on nearly all B-cell malignancies. Additionally, CD19 is
only expressed in the B-cell lineage and not in any other lineages or
tissues. These malignancies include forms of cancer such as acute
lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL),
and many different forms of lymphoma

46. TOXICITY
cytokine release syndrome (CRS), neurological toxicity, On-
target/Off-Tumour Recognition, insertional mutagenesis and
anaphylaxis.
CRS is a condition in which the immune system is activated and
releases an increased number of inflammatory cytokines. The clinical
manifestations of this syndrome include: high fever, fatigue, myalgia,
nausea, tachycardia, capillary leakages, cardiac dysfunction, hepatic
failure and renal impairment.

47. The first two FDA approved CAR-T therapies were targeted at CD19
(found on many types of lymphoma cells; mainly B-cell lymphomas).
They are approved for relapsed/refractory diffuse large B-cell
lymphoma (DLBCL) for axicabtagene ciloleucel and
relapsed/refractory B-cell precursor acute lymphoblastic leukemia
(ALL) for tisagenlecleucel.[