Table 3.
Detailed characteristics of carriers of P/LP GVs
| GV | Patient ID | Age, y | Diagnosis | Cytogenetics | Somatic mutations | Outcome | Survival |
|---|---|---|---|---|---|---|---|
| DDX41, c.804delG | AQ5388 | 72 | AML with maturation | 46,XY | DDX41 | Primary refractory AML, to 3 low-intensity regimes (DEC + sabatolimab, VEN + azacytidine, DHODi) | 44 mo (DOD) |
| DDX41, c.1015C>T | AQ5389 | 61 | AML, myelodysplasia related | 46,XY | DNMT3Ax2, STAG2, PTPN11, DDX41, ETV6, MLL-PTD, FLT3-TKD | CR1 after induction therapy (I + C + MIDO), with early relapse (<6 mo). CR2 after salvage therapy, followed by alloHCT, with subsequent second refractory relapse | 28 mo (DOD) |
| ATM, c.1110C>G | AQ5357 | 57 | Myeloid sarcoma | 46,XX | STAG2x2, TET2, ASXL1, EZH2, ATM | CR after induction therapy (I+C), followed by alloHCT (CR1). Extensive cGvHD | 64 mo (CR+) |
| ATM, c.2672C>G | AQ5355 | 59 | AML, myelodysplasia related | 46,XY,del(7)(?)[19]/46,XY[1] | RUNX1x2, ASXL1, EZH2, KIT, NF1 | CR after induction therapy (I + C), followed by alloHCT (CR1). Subsequent relapse (+13 mo) | 26 mo (DOD) |
| ATM, c.4148C>A | AQ5358 | 47 | Acute monocytic leukemia | 46,XX | IDH1, SRSF2 | Primary refractory AML to 4 therapy lines (I + C, HiDAC + idasanutlin, MIDAM-GO, and olutasidenib). CR obtained after alloHCT, performed in refractory status | 34 mo (CR+) |
| CHEK2, c.593-1G>T | AQ5329 | 45 | AML with minimal differentiation | 46,XX | SF3B1 | CR1 after induction therapy (I + C), followed by alloHCT (CR1) | 117 mo (CR+) |
| FANCM, c.5791C>T | AQ5380 | 56 | AML with minimal differentiation | 46,XY | RUNX1x2, FLT3-ITD, SRSF2, SETBP1 | CR1 after induction therapy (IDICE), with subsequent relapse, refractory to salvage therapy | 10 mo (DOD) |
| FANCA, c.2529C>G | AQ5336 | 58 | AML, myelodysplasia related | 46,XY | RUNX1, BCOR | CR1 after induction therapy (I + C), followed by alloHCT (CR1). Dead because of bilateral pneumonia | 9 mo (NRM) |
| SBDS, c.258+2T>C | AQ5325 | 45 | AML without maturation | 46,XX | None | CR1 after induction therapy (IDICE), followed by alloHCT | 134 mo (CR+) |
| DNAJC21, c.544C>T | AQ5361 | 58 | AML with minimal differentiation | - | RUNX1x2, NRASx2, KRAS | CR1 after induction therapy (I + C), followed by alloHCT (CR1) | 40 mo (CR+) |
| CSF3R, c.296_299delTCTC | AQ5347 | 60 | AML, myelodysplasia related | 79-90,XXX,-X,-3,-5,-5,-8,-10,-10,-13,-14,-15,+16,i(17)(q10),-17,-18,der(19),der(19),-21,-21,-22,+mar1,+mar2[cp18]/46,XX[2] | DNMT3A, IDH1, TP53 | Primary refractory AML to 2 lines of therapy (ICOG-07, FLAG-IDA). CR after alloHCT but early relapse after alloHCT (+3 mo) | 9 mo (DOD) |
cGvHD, chronic graft-versus-leukemia disease; CR1, first complete response; CR2, second complete response; CR+, sustained complete response; DEC, decitabine; DHODi, dihydroorotate dehydrogenase inhibitor; DOD, dead of progression; FLAG-IDA, fludarabine + high-dose cytarabine + G-CSF–idarubicin; HiDAC, high-dose cytarabine; I + C, idarubicin + cytarabine; ICOG-07, idarubicin,cytarabine, gemtuzumab ozogamicin; IDICE, idarubicin, intermediate-dose cytarabine, etoposide; MIDAM-GO, mitoxantrone, intermediate-dose cytarabine, gemtuzumab ozogamicin; MIDO, midostaurin; NRM, nonrelapse mortality; VEN, venetoclax.