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.