Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
Journal website https://jh.elmerpub.com

Original Article

Volume 13, Number 6, December 2024, pages 268-277

Retrospective Study of CD20 Expression Loss in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Figures

Figure 1.
↓  Figure 1. Flow diagram of patient eligibility.
Figure 2.
↓  Figure 2. Rate of CD20 expression loss at relapse by lymphoma type.
Figure 3.
↓  Figure 3. Immunohistochemistry images for a marginal zone lymphoma with complete CD20 loss showing (a) CD20 expression at diagnosis, (b) CD20 negativity at second relapse, (c) PAX5 positivity, thereby confirming B-cell lineage, at second relapse.
Figure 4.
↓  Figure 4. Immunohistochemistry image for a diffuse large B-cell lymphoma with partial weak CD20 expression at first relapse, representing partial CD20 loss. A subset of large lymphoma cells are weakly positive for CD20 (wide arrow), while the background small B cells are strongly positive for CD20 (thin arrow).

Tables

↓  Table 1. Demographics for Patients Who Received Treatment (n = 243)
 
Demographics
CNS: central nervous system.
Gender
  Males 144 (59.3%)
  Females 99 (40.7%)
Age at diagnosis (years)
  Median 56
  Range 19 - 94
Ethnicity/race
  Hispanic 160 (65.9%)
  White/European 34 (14.0%)
  Black/African-American 27 (11.1%)
  Asian 15 (6.2%)
  Other 7 (2.9%)
Stage
  Stage I 27 (11.1%)
  Stage II 55 (22.6%)
  Stage III 28 (11.5%)
  Stage IV 111 (45.7%)
  Primary CNS 5 (2.1%)
  Unknown 17 (7.0%)

 

↓  Table 2. Cohort of Patients by Histology
 
Number of patients (% cohort) CRR to first-line treatment Primary refractory diseasea Relapse after CRb Relapsed/refractory Number of patients with biopsy at relapse (% cohort)
aPrimary refractory disease includes patients with partial remission, stable disease, or progressive disease after first-line treatment. bAmong patients with initial CR to first-line treatment. cDouble expressor, triple expressor, or HGBCL-NOS. CR: complete remission; CRR: complete remission rate; DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; HGBCL: high-grade B-cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; NOS: not otherwise specified; PCNSL: primary central nervous system lymphoma; PMBCL: primary mediastinal B-cell lymphoma.
Overall 243 70.8% 29.2% 22.1% 44.9% 60
DLBCL 127 (52.3%) 80.3% 19.7% 16.7% 33.1% 20 (33.3%)
FL 34 (14.0%) 76.5% 23.5% 46.2% 58.9% 18 (30.0%)
MZL 18 (7.4%) 55.6% 44.4% 40.0% 66.7% 10 (16.7%)
HGBCLc 16 (6.6%) 25.0% 75.0% 0% 75.0% 3 (5.0%)
MCL 11 (4.5%) 36.4% 63.6% 50.0% 81.2% 6 (10.0%)
PCNSL 5 (2.1%) 40.0% 60.0% 50.0% 80.0% 1 (1.7%)
PMBCL 4 (1.6%) 100% 0% 25.0% 25.0% 1 (1.7%)
Burkitt 4 (1.6%) 75.0% 25.0% 0% 25.0% 0 (0%)
Plasmablastic 2 (1.6%) 50.0% 50.0% 100% 100% 1 (1.7%)
NOS/other 22 (9.1%) 69.6% 30.4% 0% 30.4% 0 (0%)

 

↓  Table 3. CD20 Expression Analysis by Relapse
 
CD20 expression First relapse (n = 52) Second relapse (n = 13) Third relapse (n = 4) Fourth relapse (n = 3) Fifth relapse (n = 2)
Positive 48 11 4 3 1
Partial 3 1 0 0 0
Negative 1 1 0 0 1
Rate of CD20 expression loss 7.7% 15.4% 0% 0% 50%

 

↓  Table 4. Patients With Complete or Partial Loss of CD20 Expression (n = 7)
 
Patient and lymphoma characteristics Biopsy at diagnosis First-line treatment First relapse biopsy and treatment Second relapse biopsy and treatment Third relapse and later
BR: bendamustine + rituximab; CR: complete remission; DAREPOCH: dose-adjusted rituximab + etoposide + prednisone + vincristine + cyclophosphamide + doxorubicin; DLBCL: diffuse large B-cell lymphoma; F: female; FCR: fludarabine + cyclophosphamide + rituximab; Flow: flow cytometry; FR: fludarabine + rituximab; HGBCL: high-grade B-cell lymphoma; ICE: ifosfamide + carboplatin + etoposide; M: male; PR: partial remission; PET: positron emission tomography; PD: progression of disease; R1: first relapse; R2: second relapse; R3: third relapse; R4: fourth relapse; R5: fifth relapse; RCHOP: rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone; RICE: rituximab + ifosfamide + carboplatin + etoposide; SD: stable disease; SCT: stem cell transplant.
1) 51M
DLBCL
ABC type
Stage IV
Partial CD20 loss at R1 		Lymph node: IHC CD20(+) RCHOP => CR Lymph node: IHC CD20(+), Flow CD20(+) dim
RICE => PD		 Death 3 months after R1
2) 33M
DLBCL
ABC type
Stage IV
Partial CD20 loss at R1 		Lymph node: IHC CD20(+) RCHOP => CR Lymph node: IHC CD20(+) weak
RICE => PR
Autologous SCT => CR		 Alive 70 months after R1
3) 47M
Follicular
Stage IV
CD20 loss at R1		 Bone marrow: IHC CD20(+), Flow CD20(+)
Chest wall mass: IHC CD20(+), Flow CD20(+)		 RCHOP + rituximab maintenance
=> PD		 Lymph node: IHC CD20(-), transformation to HGBCL
RICE => PD		 Death 3 months after R1
4) 54F
Marginal zone
Stage IV
Partial CD20 loss at R1		 Bone marrow: IHC CD20(+), Flow CD20(+) Rituximab
=> PD		 Bone marrow: IHC CD20(-), Flow CD20(+)
Ibrutinib => PD		 Death 4 months after R1
5) 56F
Follicular
Stage IV
CD20 loss at R2		 Lymph node: IHC CD20(+)
Bone marrow: IHC CD20(+)		 RCHOP + rituximab maintenance
=> CR		 No biopsy, relapse on PET
BR => PR		 Lymph node: IHC CD20(-), transformation to DLBCL
Peripheral blood: Flow CD20(-), no evidence of transformation
ICE => PD		 Death 3 months after R2
6) 58M
Marginal zone
Stage III
Partial CD20 loss at R2		 Orbital mass: IHC CD20(+) FCR => CR Biopsy results unavailable
FCR => CR		 Lymph node: IHC CD20(-), Flow CD20(+) dim, transformation to DLBCL
RCHOP => PD		 Death 5 months after R2
7) 60M
Marginal zone
Stage IV
CD20 loss at R5		 Peripheral blood: IHC CD20(+), Flow CD20(+)
Bone marrow: IHC CD20(+), Flow CD20(+)		 RCHOP => PR Bone marrow: IHC CD20(+), Flow CD20(+)
FR => PR		 Peripheral blood: Flow CD20(+)
Spleen: IHC CD20(+), Flow CD20(+)
Idelalisib + splenectomy => SD		 R3: Peripheral blood: Flow CD20(+)
Ibrutinib => PD
R4: Peripheral blood: Flow CD20(+)
Bone marrow: IHC CD20(+)
Bendamustine/ofatumumab + ofatumumab maintenance => PD
R5: Peripheral blood: Flow CD20(-)
Abdominal wall mass: IHC CD20(-), Flow CD20(-)
Duodenal mass: IHC CD20(-)
ICE => PD
Death 4 months after R5