Table 3.
Clinical outcomes in patients with complex ALK rearrangements who received targeted therapy
| Case | DNA-based NGS | RNA-based NGS | IHC | FISH | Other variants | Matched treatment | Optimal response |
|---|---|---|---|---|---|---|---|
| 1 |
EML4-intergenic (intron13: intergenic) WDR43-ALK (3′ intron1: 3′ intron19) |
EML4-ALK (exon13: exon20) |
ALK+ | N/A | None | Crizotinib | PR |
| 3 |
EML4-intergenic (intron6: intergenic) PLXNA4-ALK (3′ intron3: 3′ intron19) intergenic-EML4 (intergenic: intron6) |
EML4-ALK (exon6: exon20) |
ALK+ | + |
ALK p.T1012M ROS1 p.E1902K TP53 p.R337C TSC2 p.A678T |
Crizotinib | PR |
| 5 |
EML4-ALK (5′ intron6: 5′ intron19) ALK-ALK (3′ intron18: 3′ intron19) IL1RAPL2-ALK (5′ intron6: 5′ intron18) ALK-PTCHD1 (3′ intron18: 3′ intron1) |
EML4-ALK (exon6: exon20) |
ALK+ | + |
GNAS p.A175T TP53 splicing pathogenic |
Alectinib | CR |
| 6 |
EML4-ALK (intron6ins39: intron4) ALK-ALK (intron4ins57: intron19) |
N/A | N/A | N/A |
ROS1 p.E1902K SMAD4 p.N129H |
Crizotinib | PR |
| 8 |
EML4-EML4 (5′ intron6: 5′ intron6) EML4-ALK (3′ intron6ins4: 3′ intron19) |
EML4-ALK (exon6: exon20) |
ALK+ | + |
TP53 p.R273C NOTCH3 p.A38Lfs |
Crizotinib | PD |
| 10 |
EML4-NEB (intron13: intron24) NEB-ALK (intron24: intron19) |
EML4-ALK (exon13: exon20) |
ALK+ | + | None | Crizotinib | PR |
| 13 |
EML4-ZNF362 (intron13: intron1) ZNF362-ALK (intron1: intron19) |
EML4-ALK (exon13: exon20) |
ALK+ | N/A | None | Alectinib | PR |
| 14 |
EML4-RPIA (intron13: intron3) MAP4K3-ALK (intron2: intron19) |
EML4-ALK (exon13: exon20) |
ALK+ | + | None | Crizotinib | SD |
N/A: not available; +: positive results; −: negative results; CR: complete response; PR: partial response; SD: stable disease; PD: progression disease