Table 1:
Treatment characteristics, outcomes and adverse effects of studies of essential thrombocythemia
| Author (ref) | Year | Treatment and treatment schedule | N (patients) | Outcomes | Outcome definition | Adverse effects (AE) |
|---|---|---|---|---|---|---|
| Abegg-Werter et al.19 | 1990 | rIFN-α−2c 5×106 IU 3–7 days per week based on response and tolerability | 6 | ORR: 100% (CHR: 83%; PHR: 17%) | CHR: platelet count <350×109/L PHR: platelet count 350–600×109/L |
100% with adverse events, no grading provided |
| Alvarado et al.20 | 2003 | Peg-IFN-α−2b 1.5–6.0 μg/kg once weekly based on response and tolerability | 11 | ORR: 100% (CHR: 100%, PHR: 0%) | CHR: platelet count <400×109/L, no thromboembolic events PHR: platelet count 400–600×109/L, no thromboembolic events |
0 thromboembolic events, otherwise not reported |
| Bentley et al.21 | 1999 | IFN-α−2a 3–9×106 IU daily; maintenance treatement with IFN-α−2a 3×106 IU t.i.w. | 34 | ORR: 79% (CHR: 50%; PHR: 28%) | CHR: platelet count <400×109/L PHR: platelet count 400–600×109/L |
No grade ≥3 adverse events; 28% discontinuation rate due to adverse effects |
| Berte et al.47 | 1996 | IFN-α−2a or IFN-α−2b 3×106 IU t.i.w. | 12 | ORR: 83% (CHR: 42%; PHR: 42%) | CHR: platelet count <400×109/L, no splenomegaly PHR: platelet count 400–600×109/L; >50% reduction in splenomegaly |
No grading provided, 1 treatment discontinuation due to AE |
| Cervantes et al.22 | 1991 | IFN-α−2b 3–5×106 IU daily; maintenance treatement with IFN-α−2b 3×106 IU 2–4 days per week | 13 | ORR: 100% (CHR: 100%, PHR: 0%) | CHR: platelet count <400×109/L PHR: not defined |
11 out of 13 patients with flu-like symptoms, no other AE reported |
| Giles et al.23 | 1990 | rIFN-α−2a or IFN-α−2b 3–6×106 IU daily; maintenance treatement with IFN-α−2b 3×106 IU t.i.w | 22 | ORR: 86% (CR and PR not defined) | Not defined | All patients with AE, no grading provided, 3 patients disconitnued treatment due to AE |
| Giralt et al.24 | 1991 | IFN-α−2b 3×106 IU daily; dose reduction based on tolerability; maintenance treatment with IFN-α−2b 3–5×106 IU twice weekly | 13 | ORR: 69% (CR: 15%, PR: 54%) | CR: platelet count <450×109/L with resolution of splenomegaly and symptoms PR: reduction in platelet count (not defined) with spleen size (>50%) and absence of symptoms |
12 patients with flu-like symptoms, 7 patients with leukopenia, and 3 patients with neurological, metabolic and hepatic AE |
| Gisslinger et al.48 | 1991 | IFN-α−2c 6–45×106 IU/week; dose adjustments based on efficacy and tolerability | 20 | ORR: 85% (CHR: 65%, PHR: 20%) | CHR: platelet count <440×109/L PHR: platelet count reduction >50% but still >440×109/L |
No grading provided, 4 treatment discontinuations due to AE |
| Kasparu et al.25 | 1992 | rIFN-α−2b 5×106 IU daily; maintenance treatement with IFN-α−2b every other day (unspecified dose) with subsequent taper | 14 | ORR: 100% (CHR: 86%, PHR: 0%) | Definition according to polycythemia vera study group86 CHR: platelet count <450×109/L Good PHR: platelet count 450–600×109/L Poor PHR: platelet count 600–1000×109/L |
All patients with AE, no grading provided, 1 thromboembolic event, 3 patients disconitnued due to AE |
| Langer et al.30 | 2005 | Peg-IFN-α−2b 25–150 μg once weekly; dose adjustments based on efficacy and tolerability | 36 | ORR: 75% (CHR: 67%, PHR: 8%) | CHR: platelet count <450×109/L PHR: platelet count 450–600×109/L |
10 patients discontinued due to AE |
| Lopes et al.31 | 1992 | IFN-α−2b 3×106 IU/m2 daily or 3–5×106 IU/m2 t.i.w.; 3×106 IU/m2 t.i.w. for maintenance |
7 | ORR: 100% (CR: 71%, PR: 29%) | CR: resolution of symptoms, splenomegaly, and normal platelet count PR: >50% reduction in baseline platelet count and clinical improvement |
5 patients with flu-like symptoms, 3 thromboembolic events |
| Gowin et al.26 | 2012 | Peg-IFN-α−2a starting dose 22.5–180 μg/week (median: 80 μg/week); maximum dose: 30–300 μg/week (median: 90 μg/week) | 46 | ORR: 78% (CR: 63%; PR: 15%) | 2009 ELN response criteria87 | Not reported separately |
| Gowin et al.27 | 2017 | Peg-IFN-α−2a starting dose 45–90 μg/week (median: 45 μg/week); maximum dose: 45–275 μg/week (median: 90 μg/week) | 20 | ORR: 65% (CR: 25%; PR: 20%) | 2013 ELN/IWG-MRT response criteria77 | 1 thromboembolic event; no other adverse effects reported separately |
| Huang et al.28 | 2014 | IFN-α−2b 3×106 IU t.i.w. for 2 years; 5×106 IU twice per week for maintenance | 123 | ORR: 73% (CHR: 29%; PHR: 45%) | CHR: normalization of platelet count and no thromboembolic events PHR: >50% reduction in platelet count but >400×109/L |
66 patients with any AE, 11 patients with ≥3 grade |
| Jabbour et al.29 | 2007 | Peg-IFN-α−2b 2–3 μg/kg/week; dose reduction for toxicity permitted | 13 | ORR: 69% (CHR: 54%; PHR: 15%) | CHR: platelet count <440×109/L PHR: >50% reduction of platelet count without achieving normal levels |
Not reported separately for ET patients |
| Lazzarino et al.32 | 1988 | IFN-α−2b 1–4 ×106 IU daily; dose adjustments based on efficacy and tolerability | 26 | ORR: 89% (CHR: 62%; PHR: 27%) | CHR: normalization of all blood counts and resolution of splenomegaly PHR: platelet count 400–600×109/L, WBC<20×109/L, reduction in spleen size by >50% |
Not reported separately for ET patients |
| Lindgren et al.33 | 2018 | Peg-IFN-α−2a 67.5–135 μg/week (median: 90 μg/week) Peg-IFN-α−2b 30–80 μg/week (median: 50 μg/week) IFN-α−2b 1.2–20×106 IU/week (median: 9×106 IU/week) |
43 | ORR: 100% (CHR: 70%; PHR: 30%) | CHR: normalization of all blood counts and resolution of symptoms PHR: platelet count <600×109/L or >50% reduction |
Not reported |
| Masarova et al.34 | 2017 | Peg-IFN-α−2a 90–450 μg/week | 40 | ORR: 80% (CHR: 73%; PHR: 3%) | Hematologic responses based on 2009 ELN response criteria87 | 100% with any adverse event; 4 patients with transformation to AML or myelofibrosis |
| Middelhoff et al.35 | 1992 | IFN-α (subtype not specified) induction with 4×106 IU/m2; maintenance with 3–6×106 IU every other day | 6 | ORR: 100% (CHR: 50%; PHR: 50%) | CHR: platelet count <400×109/L PHR: >50% decrease in platelet count |
Not reported |
| Pogliani et al.36 | 1995 | rIFN-α−2b 2–5×106 IU/m2 t.i.w.; dose adjustments based on response and tolerability | 25 | ORR: 80% (CHR: 56%; PHR: 24%) | CHR: platelet count <450 ×109/L PHR: platelet count <600 ×109/L |
9 treatment discontinuation due to AE |
| Radin et al.37 | 2003 | IFN-α2 2–5×106 IU/m2 daily; dose reductions based on adverse events | 17 | ORR: 88% (CR: 6%; PR: 82%) | CR: normalization of blood counts, normal blood smear, normal bone marrow, resolution of splenomegaly, and no thrombotic or hemorrhagic events PR: any one of (1) Hgb >10g/dL or (2) platelet count <800 ×109/L without thrombotic or hemorrhagic events or (3) spleen size reduction >50% |
96 adverse events in 17 patients, 11 patients with ≥3 grade |
| Rametta et al.38 | 1994 | IFN-α−2b 3×106 IU daily; maintenance treatment with IFN-α−2b 3×106 IU t.i.w. | 25 | ORR: 92% (CHR: 52%; PHR: 40%); 18% with reduction of splenomegaly | CHR: platelet count <400 ×109/L PHR: platelet count <600 ×109/L |
18 patients with flu-like symptoms, otherwise not reported; no treatment discontinuation due to AE |
| Saba et al.39 | 2005 | rIFN-α−2a 5×106/m2 IU daily; dose increase to 10×106/m2 IU daily permitted | 20 | ORR: 75% (CHR: 70%, CR: 30% ; PHR: 5%) | CHR: platelet count <440 ×109/L CR: CHR and normalization of bone marrow pathology PHR: >50% reduction in platelet count |
3 treatment discontinuation due to AE |
| Sacchi et al.40 | 1991 | IFN-α−2b 3×106 IU daily; reduced to IFN 3×106 IU 1–3x per week based on response | 35 | ORR: 89% (CHR: 46%; PHR: 43%) | CHR: platelet count <400 ×109/L PHR: platelet count <600 ×109/L |
100% of patients with flu-like symptoms, no grading provided; 3 treatment discontinuations due to AE |
| Sacchi et al.41 | 1998 | IFN-α n-1 3–6×106 IU daily | 11 | ORR: 100% (CHR: 91%; PHR: 9%); spleen size reduction in 2 out of 4 patients | CHR: platelet count <400 ×109/L PHR: platelet count <600 ×109/L |
9 patients with flu-like symptoms, otherwise not reported; no treatment discontinuation due to thyroiditis |
| Seewann et al.42 | 1991 | IFN-α−2b 3–5×106 IU daily; maintenance treatment for up to 2 years with IFN 3–5×106 IU t.i.w. | 19 | ORR: 68% (CHR: 68%; PHR: 0%) | CHR: platelet count <450 ×109/L PHR: >50% reduction in platelet count |
3 treatment discontinuation due to AE |
| Turri et al.43 | 1991 | IFN-α−2a 3×106 IU daily; maintenance treatement for responding patients with IFN-α2a 3×106 IU t.i.w. | 9 | ORR: 67% (CHR: 56%, PHR: 11%) | CHR: platelet count <450 ×109/L PHR: >50% reduction in platelet count |
Not reported |
| Verger et al.44 | 2015 | Peg-IFN-α 230–496 μg/month (mean dose) | 31 | ORR: 100% (CHR: 77%, PHR: 23%) | Hematologic responses based on 2009 ELN response criteria87 | 6 treatment discontinuation due to AE |
| Yataganas et al.45 | 1991 | IFN-α−2b 3–5×106 IU daily; maintenance treatement with IFN-α−2b 3×106 IU t.i.w. | 9 | ORR: 100% (CHR: 67%, PHR: 33%), 0/3 patients with improvement in splenomegaly | CHR: platelet count <400 ×109/L PHR: platelet count <600 ×109/L |
All patients with adverse events, no grading provided |
| Zhang et al.46 | 2014 | IFN-α−2b 300 U t.i.w.; maintenance treatment IFN-α−2b 300 U once or twice per week | 20 | ORR: 90% (CR: 40%, PR: 50%) | CR: normalization of blood counts and resolution of splenomegaly PR: improvement in blood counts by >50% |
4 thromboembolic events, otherwise not reported |
AE – adverse events; CHR – complete hematologic response; CR – complete remission; ELN – European Leukemia Network; IFN – Interferon; IU – international units; IWG-MRT - International Working Group-Myeloproliferative Neoplasms Research and Treatment; t.i.w. – three times a week, PHR – partial hematologic response; partial response – partial remission; rIFN – recombinant interferon; U - unit