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
  Males144 (59.3%)
  Females99 (40.7%)
Age at diagnosis (years)
  Median56
  Range19 - 94
Ethnicity/race
  Hispanic160 (65.9%)
  White/European34 (14.0%)
  Black/African-American27 (11.1%)
  Asian15 (6.2%)
  Other7 (2.9%)
Stage
  Stage I27 (11.1%)
  Stage II55 (22.6%)
  Stage III28 (11.5%)
  Stage IV111 (45.7%)
  Primary CNS5 (2.1%)
  Unknown17 (7.0%)

 

Table 2. Cohort of Patients by Histology
 
Number of patients (% cohort)CRR to first-line treatmentPrimary refractory diseaseaRelapse after CRbRelapsed/refractoryNumber 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.
Overall24370.8%29.2%22.1%44.9%60
DLBCL127 (52.3%)80.3%19.7%16.7%33.1%20 (33.3%)
FL34 (14.0%)76.5%23.5%46.2%58.9%18 (30.0%)
MZL18 (7.4%)55.6%44.4%40.0%66.7%10 (16.7%)
HGBCLc16 (6.6%)25.0%75.0%0%75.0%3 (5.0%)
MCL11 (4.5%)36.4%63.6%50.0%81.2%6 (10.0%)
PCNSL5 (2.1%)40.0%60.0%50.0%80.0%1 (1.7%)
PMBCL4 (1.6%)100%0%25.0%25.0%1 (1.7%)
Burkitt4 (1.6%)75.0%25.0%0%25.0%0 (0%)
Plasmablastic2 (1.6%)50.0%50.0%100%100%1 (1.7%)
NOS/other22 (9.1%)69.6%30.4%0%30.4%0 (0%)

 

Table 3. CD20 Expression Analysis by Relapse
 
CD20 expressionFirst relapse (n = 52)Second relapse (n = 13)Third relapse (n = 4)Fourth relapse (n = 3)Fifth relapse (n = 2)
Positive4811431
Partial31000
Negative11001
Rate of CD20 expression loss7.7%15.4%0%0%50%

 

Table 4. Patients With Complete or Partial Loss of CD20 Expression (n = 7)
 
Patient and lymphoma characteristicsBiopsy at diagnosisFirst-line treatmentFirst relapse biopsy and treatmentSecond relapse biopsy and treatmentThird 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 => CRLymph 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 => CRLymph 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 => CRBiopsy 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 => PRBone 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