The University of Texas MD Anderson Cancer Center, Houston, TX
Prithviraj Bose , Jayastu Senapati , Lucia Masarova , Naveen Pemmaraju , Guillermo Montalban Bravo , Sherry Pierce , Lingsha Zhou , Guillermo Garcia-Manero , Hagop M. Kantarjian , Srdan Verstovsek
Background: Splicing factor 3B subunit 1 (SF3B1) mutations have been shown to confer a unique phenotype in MDS and MDS/MPN overlap syndromes, with ring sideroblasts, thrombocytosis and favorable prognosis. In myelofibrosis (MF) the frequency of SF3B1 mutation is <10% and may play a less important role in disease outcomes (Lasho et. al, Leukemia, 2011). Methods: We retrospectively analyzed all patients (pts) with WHO-defined MF (primary, including pre-fibrotic MF, or progressed from PV or ET) seen at our center from Jan. 2017 through Jul. 2021. We compared disease phenotypes, MPN driver and co-occurring mutations, cytogenetics, dynamic IPSS (DIPSS) score, transfusion requirements, treatment characteristics and survival outcomes between patients with SF3B1-mutated (SF3B1+) and -wild type (SF3B1-) MF. Results: A total of 381 pts were identified, 29 (8%) of whom were SF3B1+. There were similar frequencies of JAK2, CALR, MPL mutations and “triple negative” MF in the 2 groups (Table). The median number of SF3B1 mutations was 1 (range, 1-2); K666N being the most common (52%). The 2 groups were similar in regard to their baseline hemoglobin, white blood cell counts, platelets, co-occurring mutations, symptom burden and DIPSS but more SF3B1+ pts were PRBC transfusion-dependent at presentation than SF3B1- pts (38% vs. 15%, p=0.003). At a median follow up of 17.2 months for the entire cohort (range, 0.1- 52.2 mos., 22.6 mos. for SF3B1+ and 16.8 mos. for SF3B1-), 41 pts had died [14% SF3B1+ and 10% SF3B1-, p=0.5] and 7 pts (1 SF3B1+ and 6 SF3B1-) had leukemic transformation. The median estimated OS was 230 months for SF3B1- vs. not reached for SF3B1+ pts (p = 0.6). Conclusions:SF3B1 mutation is an uncommon event in MF and does not substantially affect disease phenotype and outcomes. MF pts with SF3B1 mutation are more likely to be PRBC transfusion dependent.
Characteristics | SF3B1+ (N= 29) | SF3B1- (N= 352) | P value |
---|---|---|---|
N (%) /Median[range] | |||
Age (yrs.) | 72 [54-91] | 69 [21-89] | |
Males | 24 (83) | 202 (57) | |
Diagnosis | |||
Primary MF Post ET MF Post PV MF | 21 (72) 5 (17) 3 (1) | 226 (64) 69 (20) 57 (16) | |
Baseline CBC | |||
Hb (g/dl) WBC (109/L) Platelet (109/L) | 9.7 [6.9-18.4] 8.3 [1.3-73.3] 230 [19-1188] | 10.5 [5.5-17.6] 8.5 [1.1-212.1] 216 [1-1271] | 0.4 0.9 0.5 |
Driver mut. | |||
JAK2CALRMPL Triple negative JAK2 allele burden | 18 (62) 5 (17) 3 (10) 3 (10) n=28 45 [1-81] % | 214 (60) 82 (23) 29 (8) 32 (9) n=343 47 [1-99] % | 0.9 0.6 0.7 0.7 0.5 |
Co-mut. | |||
Splicing mutations (SRSF2, ZSRS2, U2AF1) Epigenetic mutations (ASXL1, TET2, IDH1/2, DNMT3A, EZH2) TP53 mutation | n=20 3 (15) 15 (75) 2 (10) | n=205 59 (29) 157 (76) 10 (5) | 0.3 0.9 0.3 |
CTG | |||
Non diploid karyotype | n=25 12 (48) | n=264 102 (39) | 0.4 |
BM fibrosis | |||
Grade 3 | n=29 3 (24) | n=274 113 (41) | 0.001 |
DIPSS | |||
Low Intermediate 1 Intermediate 2 High | 1 (3) 10 (34) 15 (52) 3 (10) | 13 (4) 153 (43) 119 (34) 67 (19) | 0.3 |
Transfusion dependency | |||
PRBC Platelet | 11 (38) 0 (0) | 52 (15) 4 (1) | 0.003 0.99 |
Treatment | |||
Ruxolitinib Sotatercept | 14 (48) 2 (14) | 152 (43) 9 (3) | 0.7 0.2 |
Events | |||
Leukemic transformation Death | 1 (3) 4 (14) | 6 (2) 37 (10) | 0.4 0.2 |
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