CD20 variants identified by WES in pre-mosunetuzumab biopsy samples and in paired biopsy samples at progression
Variants before mosunetuzumab . | ||||||
---|---|---|---|---|---|---|
Patient . | Protein position and amino acid . | Domain . | Variant class . | CD20 IHC . | CD20+PAX5+ (%) . | BOR . |
1 | Q187H | EC | Missense | CD20+ | 81.6 | CR |
2 | G53E | TM | Missense | CD20+ | CD20++ | CR |
3 | L66fs | TM | Frameshift | CD20+ | 42.3 | PD |
L66R | TM | Missense | ||||
IL138-139fs | TM | Shift, truncating | ||||
4 | M58K | TM | Missense | CD20+ | 67.2 | PD |
5 | Y77N | EC | Missense | CD20+ | 95.1 | PD |
V82G | TM | Missense | ||||
6 | A65P | TM | Missense | CD20+ | 44.3 | CR |
7 | S121∗ | TM | Stop | CD20+ | 80.6 | SD |
K175E | EC (epitope) | Missense | ||||
8 | K142∗ | TM | Stop | CD20+ | 93.2 | PR |
Variants before mosunetuzumab . | ||||||
---|---|---|---|---|---|---|
Patient . | Protein position and amino acid . | Domain . | Variant class . | CD20 IHC . | CD20+PAX5+ (%) . | BOR . |
1 | Q187H | EC | Missense | CD20+ | 81.6 | CR |
2 | G53E | TM | Missense | CD20+ | CD20++ | CR |
3 | L66fs | TM | Frameshift | CD20+ | 42.3 | PD |
L66R | TM | Missense | ||||
IL138-139fs | TM | Shift, truncating | ||||
4 | M58K | TM | Missense | CD20+ | 67.2 | PD |
5 | Y77N | EC | Missense | CD20+ | 95.1 | PD |
V82G | TM | Missense | ||||
6 | A65P | TM | Missense | CD20+ | 44.3 | CR |
7 | S121∗ | TM | Stop | CD20+ | 80.6 | SD |
K175E | EC (epitope) | Missense | ||||
8 | K142∗ | TM | Stop | CD20+ | 93.2 | PR |
Variants at progression . | |||||||
---|---|---|---|---|---|---|---|
Patient . | Visit . | Protein position and amino acid . | Domain . | Variant class . | CD20 IHC . | CD20+PAX5+ (%) . | BOR . |
9 | Pre | I80N | EC | Missense | CD20+ | 60.2 | PD |
Post | I80N | EC | Missense | CD20+ | 29.6 | ||
C167G | EC (epitope) | Missense | |||||
10 | Pre | WT | CD20+ | 65.2 | PR | ||
Post | Q187∗ | EC | Stop | CD20− | 0.73 | ||
A201fs | TM | Shift, truncating | |||||
11 | Pre | [192]-1spl | SS | Splice | CD20+ | 77.2 | PD |
Post | [192]-1spl | SS | Splice | CD20− | 1.13 | ||
12 | Pre | WT | CD20+ | 81.3 | PD | ||
Post | [54]-1spl | SS | Splice | CD20− | 0 | ||
13 | Pre | WT | CD20+ | 71.9 | PR | ||
Post | P160fs | EC | Shift, truncating | CD20− | 0.02 |
Variants at progression . | |||||||
---|---|---|---|---|---|---|---|
Patient . | Visit . | Protein position and amino acid . | Domain . | Variant class . | CD20 IHC . | CD20+PAX5+ (%) . | BOR . |
9 | Pre | I80N | EC | Missense | CD20+ | 60.2 | PD |
Post | I80N | EC | Missense | CD20+ | 29.6 | ||
C167G | EC (epitope) | Missense | |||||
10 | Pre | WT | CD20+ | 65.2 | PR | ||
Post | Q187∗ | EC | Stop | CD20− | 0.73 | ||
A201fs | TM | Shift, truncating | |||||
11 | Pre | [192]-1spl | SS | Splice | CD20+ | 77.2 | PD |
Post | [192]-1spl | SS | Splice | CD20− | 1.13 | ||
12 | Pre | WT | CD20+ | 81.3 | PD | ||
Post | [54]-1spl | SS | Splice | CD20− | 0 | ||
13 | Pre | WT | CD20+ | 71.9 | PR | ||
Post | P160fs | EC | Shift, truncating | CD20− | 0.02 |
CD20+, ≥10% CD20+PAX5+ levels; CD20−, <10% CD20+PAX5+ levels; CD20++, pathologist reviewed moderate to strong staining.
BOR, best overall response; EC, extracellular; fs, frameshift; PD, progressive disease; PR, partial response; SD, stable disease; SS, splice site; TM, transmembrane.
indicates a translation stop codon.