TABLE 2.
Main clinical and molecular features of 16 patients developing therapy‐related myeloid neoplasms and their treatments
| Type of t‐MNs | EOC status at t‐MN | Type and cycle of PARPi | Hematologic Toxicity | Duration (months) | Karyotype | Molecular biology a | Treatment administration | Type of CT administered | Allo‐HSCT | CR duration (months) | Relapse | Salvage CT | Present status (dead /alive) | Cause of death | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | EB‐2 | NED | Olaparib (41 cycles) | N G2‐3 | 2 | 46,XX, del(5)(q12q33), +13, −16, del(17)(p12pter)[cp12]/46,XX[6] |
Mut. TP53 p.(Cys242Tyr) VAF 52% |
Y | ICE → RD FLAG‐Ida → CR | Y | 5.4 | Y | Decitabine + Venetoclax → RD → phase I trial | Dead | t‐MN PD |
| 2 | AML | NED | Niraparib (10 cycles) | T G1 and N G2 | 1 | 79‐98,XXXX, +3‐4mar[cp11] |
Mut. TP53 p.(His193Leu) VAF 91% |
Y | Vyxeos | N | na | na | na | Dead | t‐MN PD |
| 3 | EB‐1 | NED | Niraparib (25 cycles) | A G2, T G2 and N G3 | 1 | 46,XX, del(5)(q22q35)[3]/45,XX, del(5)(q22q35), −7, +8, +mar[2]/45,XX, del(5)(q22q35), −7[1]/45,XX, del(5)(q22q35), −7, +8, −17[1]/46,XX[3] |
Mut. TP53 p.(Arg175His) VAF 20.05% |
Y | Vyxeos | Y | 4.7 | Y | nd | Dead | t‐MN PD |
| 4 | EB‐1 | CR | Olaparib (24 cycles) | A G2, T G2 and N G2 | 1 | 46,XX, del(5)(q22q35), −7, +8, +8, −17[10]/46,XX, del(5)(q22q35), −17[3]/46,XX[2] |
mut. TP53 p.(Arg249Thr) VAF 53.8% |
Y | Vyxeos | N | 2.8 | N | na | Dead | Heart failure |
| 5 | AML M6 | SD | Olaparib (29 cycles) | A G2 and T G3 | 1 | 46,XX[2] |
Mut. TP53 p.(His179Arg) VAF 9.6% |
Y | ICE → RD FLAG‐Ida → RD decitabine+ven | N | na | NA | Decitabine + ven → RD | Dead | t‐MN PD |
| 6 | EB‐2 | CR | Niraparib (19 cycles) | A G2, T G1, N G1 | 2 | 43,XX, t(1;12)(p21;p13), −7, −13, −16, −18, +mar[12]/46,XX[1] |
Mut. TP53 p.(Val216Met) VAF 40.55% |
Y | ICE ARA‐C 6 g/mq | Y | 4.7 | Y | Ven → RD | Dead | t‐MN PD |
| 7 | AML | SD | Rucaparib (26 cycles) | A G2, T G2, N G4 | 2 | 46,XX, del(13)(q12q14)[2]/46,XX[20] | Mut. TP53 p.(Arg273Cys) VAF 8% | Y | ICE ARA‐C 6 g/mq | Y | 49.3 | N | na | Alive | na |
| 8 | EB‐1 | NED | Olaparib (21 cycles) | A G1 T G2 | 10 | 48‐52,XX, +1, −5, −6, +8, +11, der(17)t(17;2)(p11.2;2), +19 + 22, +2 mar[10] |
Mut. TP53 p.(Pro151Arg) VAF 53.3% |
Y | ICE | Y | 15.6 | N | na | Dead | TRM (PTLD) |
| 9 | EB‐2 | SD | Niraparib (21 cycles) | Pancytopenia and blasts | Immediate hematologic consult | 46,XX,t(3;21)(q26;q22)[3]/46,XX[17] |
mut. SH2B3 tras fus RUNX1(4)‐MECOM(2 |
Y | Vyxeos | Y | 14.3 | N | na | dead | TRM (GVHD) |
| 10 | EB‐1 | CR | Olaparib (33 cycles) | T G1 and A G2 | 10 | 44XX −7, del5, t(5;18)(q11;2); del5(q11),‐18[11/46xx] | nd | Y | 5‐aza | Y | 48.7 | N | na | Alive | na |
| 11 | AML | SD | Olaparib (18 cycles) | A G2, T G2 and N G1 | 1 | 43‐45,XX, −3, del(5)(q22q35),der(7) t(3;7)(2q21;2p21), −17, add(21)(q22), −22, +2mar[3]/46,XX[12] |
Mut.TP53 p.(Met246Val) VAF 6.65% mut, TP53 p.(Ser241Tyr) VAF 33.4% |
Y | 5‐aza + ven → RD | N | na | na | na | Dead | t‐MN PD |
| 12 | MSD‐MLD | CR | Rucaparib (27 cycles) | T G1 | 2 | 46,XX, del(5)(q12q33)[11]/46,XX[1] |
Mut.TET2mut. TP53 p.(Ser99Glufs*48) VAF 24.69% |
N | — | N | na | na | na | Alive | na |
| 13 | MSD‐MLD | PD | Niraparib (11 cycles) Olaparib(3 cycles) | A G3, T G2, N G2 | 9 | 45,XX, del(5)(q213;q234), −7[4]/46,XX[16] |
Mut. U2AF1 mut. TP53 p.(Leu194Hisfs*14 VAF 61.47% |
N | — | N | na | na | na | Dead | Sudden death |
| 14 | MSD‐MLD | SD | Niraparib (11 cycles) | T G4, A G2, N G1 | 5 | 45‐43,XX, del(5)(q22;q35), −7, +15[13]/39‐44,XX, del(5)(q22;q35), −7, +mar[3]/46,XX[4] |
Mut.TP53 p.(Gly244Ser) VAF 52.20% |
N | — | N | na | na | na | Dead | EOC PD |
| 15 | MSD‐MLD | PR | Olaparib (5 cycles) | N G2, T G1 | 2 | 45,XX, t(3;3)(q21;q26), −7[13]/46,XX[2] | nd | N | — | N | na | na | na | Dead | EOC PD |
| 16 | MSD‐MLD | SD | Olaparib (24 cycles) | T G4 | 2 | 46,XX[20]; in FISH del 5q | nd | N | — | N | na | na | na | Dead | Cerebral bleed |
Abbreviations: 5‐aza, 5‐azacytidine 75 mg/smq days 1‐7 q28; A, anemia; allo‐HSCT, allogeneic hematopoietic stem cell transplantation; AML M6, acute erythroblastic leukemia; AML, acute myeloid leukemia; CR, complete remission; CT, chemotherapy; PTDL, posttransplant lymphoproliferative disease; EB1, myelodysplastic syndrome with excess blasts type 1; EB2, myelodysplastic syndrome with excess blasts type 2; EOC, epithelial ovarian cancer; FLAI, Idarubicin 12 mg/smq day 1/day 3/day 5 + Fludarabine 30 mg/smq days 1‐5 + Cytarabine 2000 mg/smq days 1‐5 + GCSF from day 0; ICE, idarubicin 12 mg/smq days 1‐d3 + Cytarabine 100 mg/smq days 1‐7 + Etoposide 100 mg/smq days 1‐5; MSD‐MLD, myelodysplastic syndrome with multilineage dysplasia; Mut., mutation; N, neutropenia; N, no; na, not applicable; nd, not done, no proper material was available for analysis; NED, no evidence of disease; PARPi, poly(ADP‐ribose) polymerase inhibitors; PD, progressing disease; PR, partial remission; RD, refractory disease; SD, stable disease; T, thrombocytopenia; t‐MNs, therapy‐related myeloid neoplasms; VAF, variant allele frequency; ven, venetoclax; Vyxeos Liposomal, daunorubicin 44 mg + cytarabine 100 mg (ratio 5:1); Y, yes.
Next generation sequencing analysis of PB DNA using the Oncomine Myeloid Research Assay and the Ion Torrent S5 technology (ThermoFisher).