Long-term clonal evolution upon lenalidomide treatment in low/int-1 myelodysplastic syndromes
| Patient characteristics at baseline . | Long-term evolution . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| UPN . | Gender/age, y . | WHO . | IPSS . | Mutated genes . | Treatment . | Last follow-up, mo . | Cycle of treatment . | Major mutations . | Minor mutation(s) . | Clinical status . |
| 13 | M/62 | RCMD | Int-1 | SF3B1, TET2, DNMT3A, TET2 | Lenalidomide | 23 | C19 | Re-increase | Increase DNMT3A | Loss of efficacy |
| 33 | M/72 | RCMD | Int-1 | SF3B1, DNMT3A, TET2, DNMT3A, ASXL1 | Lenalidomide | 12 | C10 | Re-increase | Increase | Loss of efficacy |
| 54 | M/80 | RCMD | Int-1 | DNMT3A, SF3B1 | Lenalidomide | 16 | C10 | Re-increase | NA | Loss of efficacy |
| 77 | M/73 | RARS | Int-1 | SF3B1, DNMT3A, TET2, TET2 | Lenalidomide + EPO | 26 | C21 | Increase | Decrease TET2 | Loss of efficacy |
| 85 | M/74 | RCMD | Int-1 | SF3B1, TET2, TET2, RUNX1 | Lenalidomide + EPO | 23 | C20 | Stable | Decrease RUNX1 | Still responder |
| 91 | F/84 | RCMD | Low | SF3B1, DNMT3A, SF3B1 | Lenalidomide + EPO | 22 | C20 | Decrease | Increase SF3B1 ex 14 | Still responder |
| 98 | M/70 | RAEB-1 | Int-1 | SF3B1, DNMT3A, TET2, EXH2, ETV6 | Lenalidomide + EPO | 18 | C11 | Re-increase | Decrease TET2/increase EZH2 and ETV6 | Transformation |
| 110 | M/69 | RARS | Int-1 | DMT3A, SF3B1, ETV6, TET2, JAK2 | Lenalidomide | 18 | C14 | Re-increase | Increase JAK2 | Loss of efficacy* |
| 101 | M/76 | RARS | Int-1 | SF3B1, SF3B1 | Lenalidomide + EPO | 18 | C11 | Re-increase | Decrease SF3B1 | Loss of efficacy |
| 124 | M/80 | RARS | Low | SF3B1, EZH2, TET2 | Lenalidomide + EPO | 19 | C16 | Decrease | Decrease TET2 and EZH2 | Still responder |
| 130 | M/74 | RARS | Low | SF3B1, TET2, KIT | Lenalidomide | 10 | C8 | Re-increase | Decrease TET2 and KIT | Still responder |
| 17 | M/72 | RAEB-1 | ND | DNMT3A, SRSF2, TET2 | Lenalidomide + EPO | 9 | C7 | Re-increase SRSF2 | NA | Transformation |
| 19 | M/76 | RARS | Low | SF3B1, TET2, TET2, TET2 | Lenalidomide + EPO | 11 | C8 | Stable | Stable | Loss of efficacy |
| 35 | F/46 | RARS | Int-1 | SF3B1, TET2 | Lenalidomide + EPO | 18 | C16 | Re-increase SF3B1 | NA | Loss of efficacy |
| 39 | M/63 | RARS | Int-1 | DNMT3A, SF3B1 | Lenalidomide | 23 | C28 | Re-increase | NA | Loss of efficacy |
| 60 | M/78 | RCMD | Int-1 | SF3B1, TET2 | Lenalidomide + EPO | 12 | C5 | Decrease | NA | Loss of efficacy |
| 76 | M/65 | RARS | Int-1 | SF3B1, TET2 | Lenalidomide + EPO | 20 | C18 | Re-increase | Increase TET2 | Loss of efficacy |
| 79 | F/73 | RCMD-RS | Low | SF3B1, TET2, TET2 | Lenalidomide + EPO | 15 | C12 | Decrease | Decrease TET2 | Loss of efficacy |
| Patient characteristics at baseline . | Long-term evolution . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| UPN . | Gender/age, y . | WHO . | IPSS . | Mutated genes . | Treatment . | Last follow-up, mo . | Cycle of treatment . | Major mutations . | Minor mutation(s) . | Clinical status . |
| 13 | M/62 | RCMD | Int-1 | SF3B1, TET2, DNMT3A, TET2 | Lenalidomide | 23 | C19 | Re-increase | Increase DNMT3A | Loss of efficacy |
| 33 | M/72 | RCMD | Int-1 | SF3B1, DNMT3A, TET2, DNMT3A, ASXL1 | Lenalidomide | 12 | C10 | Re-increase | Increase | Loss of efficacy |
| 54 | M/80 | RCMD | Int-1 | DNMT3A, SF3B1 | Lenalidomide | 16 | C10 | Re-increase | NA | Loss of efficacy |
| 77 | M/73 | RARS | Int-1 | SF3B1, DNMT3A, TET2, TET2 | Lenalidomide + EPO | 26 | C21 | Increase | Decrease TET2 | Loss of efficacy |
| 85 | M/74 | RCMD | Int-1 | SF3B1, TET2, TET2, RUNX1 | Lenalidomide + EPO | 23 | C20 | Stable | Decrease RUNX1 | Still responder |
| 91 | F/84 | RCMD | Low | SF3B1, DNMT3A, SF3B1 | Lenalidomide + EPO | 22 | C20 | Decrease | Increase SF3B1 ex 14 | Still responder |
| 98 | M/70 | RAEB-1 | Int-1 | SF3B1, DNMT3A, TET2, EXH2, ETV6 | Lenalidomide + EPO | 18 | C11 | Re-increase | Decrease TET2/increase EZH2 and ETV6 | Transformation |
| 110 | M/69 | RARS | Int-1 | DMT3A, SF3B1, ETV6, TET2, JAK2 | Lenalidomide | 18 | C14 | Re-increase | Increase JAK2 | Loss of efficacy* |
| 101 | M/76 | RARS | Int-1 | SF3B1, SF3B1 | Lenalidomide + EPO | 18 | C11 | Re-increase | Decrease SF3B1 | Loss of efficacy |
| 124 | M/80 | RARS | Low | SF3B1, EZH2, TET2 | Lenalidomide + EPO | 19 | C16 | Decrease | Decrease TET2 and EZH2 | Still responder |
| 130 | M/74 | RARS | Low | SF3B1, TET2, KIT | Lenalidomide | 10 | C8 | Re-increase | Decrease TET2 and KIT | Still responder |
| 17 | M/72 | RAEB-1 | ND | DNMT3A, SRSF2, TET2 | Lenalidomide + EPO | 9 | C7 | Re-increase SRSF2 | NA | Transformation |
| 19 | M/76 | RARS | Low | SF3B1, TET2, TET2, TET2 | Lenalidomide + EPO | 11 | C8 | Stable | Stable | Loss of efficacy |
| 35 | F/46 | RARS | Int-1 | SF3B1, TET2 | Lenalidomide + EPO | 18 | C16 | Re-increase SF3B1 | NA | Loss of efficacy |
| 39 | M/63 | RARS | Int-1 | DNMT3A, SF3B1 | Lenalidomide | 23 | C28 | Re-increase | NA | Loss of efficacy |
| 60 | M/78 | RCMD | Int-1 | SF3B1, TET2 | Lenalidomide + EPO | 12 | C5 | Decrease | NA | Loss of efficacy |
| 76 | M/65 | RARS | Int-1 | SF3B1, TET2 | Lenalidomide + EPO | 20 | C18 | Re-increase | Increase TET2 | Loss of efficacy |
| 79 | F/73 | RCMD-RS | Low | SF3B1, TET2, TET2 | Lenalidomide + EPO | 15 | C12 | Decrease | Decrease TET2 | Loss of efficacy |
Targeted sequencing was performed before treatment and after >5 cycles of treatment in 18 patients. Major mutations are indicated in bold. For the last follow-up, number of treatment cycles is indicated. Based on the statistical analyses, evolution of major and minor mutations is expressed as increase, decrease, or stable. When major mutations initially decreased after 4 cycles of treatment and increased during long-term follow-up, the evolution of major mutations is indicated as re-increase.
C, treatment cycle; F, female; M, male; NA, not applicable; ND, not determined.
Severe adverse event (neuropathy).