Table 2:
Treatment characteristics, outcomes and adverse effects of studies of polycythemia vera
| Author (ref) | Year | Treatment and treatment schedule | N (patients) | Outcomes | Outcome definition | Adverse events (AE) |
|---|---|---|---|---|---|---|
| Crisa et al.49 | 2017 | Peg-IFN-α−2a 90–135 μg/week | 30 | ORR: 87% (CR: 70%; PR: 17%) | 2009 ELN response criteria87 | 87% with any AE, 13% with ≥3 grade AE; 3% annual discontinuation rate due to AE |
| Foa et al.50 | 1998 | rIFN-α−2a 3×106 IU/m2 t.i.w.; dose adjustments based on efficacy and tolerability permitted | 38 | ORR: 66% (CHR: 38%; PHR: 28%) 11 out of 38 patients free of phlebotomy |
CHR: (<52% in men; <47% in females) without phlebotomy PHR: >50% reduction in phlebotomy requirement |
14 treatment discontinuations due to AE; 1 patient each with transformation to AML or myelofibrosis |
| Gisslinger et al.51 | 2015 | Ropeginterferon α−2b 50–540 mg every 2 weeks (mean dose 263 μg every 2 weeks) | 51 | ORR: 90% (CR: 47%; PR: 43%); 68% molecular response; 82% free of phlebotomy | 2009 ELN response criteria87 | 45 patients with any AE, no grading provided, 12% annual treatment discontinuation rate due to AE |
| 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) | 55 | ORR: 87% (CR: 54%; PR: 33%) | 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) | 36 | ORR: 86% (CR: 8%; PR: 39%) | 2013 ELN/IWG-MRT response criteria77 | 1 thromboembolic event; no other AE reported separately |
| Heis et al.52 | 1999 | rIFN-α−2c 4–35×106 IU/week or lymphoblastoid IFN-α 9×106 IU/week | 21 | ORR: 33% (CHR: 10%; PHR: 24%) | CHR: Hct <45% without phlebotomy PHR: Hct >45% and >50% reduction in phlebotomy requirement |
40 AE in 32 patients, no grading provided; 20% annual treatment discontinuation rate due to AE |
| 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 | 64 | ORR: 70% (CR: 30%; PR: 41%) 53 out of 55 patients free of phlebotomy |
CR: normalization of CBC and spleen size, no thromboembolic events PR: >50% reduction in spleen size or phlebotomy requirement |
7 patients with ≥3 grade AE; 5.3% annual discontinuation rate due to AE |
| Jones et al.53 | 2006 | rIFN-α 2–4.25×106 IU ranging from daily to t.i.w. dosing | 7 | ORR: 100% (CHR: 86%; PHR: 14%) | CHR: Hct <45% (men) or <42% (women) and platelet count <600/mm3 without phlebotomy PHR: Hct <45% (men) or <42% (women) and platelet count 600–1000/mm3 without phlebotomy |
Not reported |
| Lindgren et al.33 | 2018 | Peg-IFN-α−2a 45–135 μg/week (median: 90 μg/week) Peg-IFN-α−2b 30–50 μg/week (median: 35 μg/week) IFN-α−2b 4.5–15×106 IU/week (median: 6.3×106 IU/week) |
43 | ORR: 64% (CHR: 60%; PHR: 4%) | CHR: Hct <45% without phlebotomoy with normal WBC and platelet count and resolution of symptoms PHR: Hct <45% or 3 other criteria |
Not reported |
| Kiladjian et al.9 | 2008 | Peg-IFN-α−2a 90–180 μg weekly | 37 | ORR: 100% (CHR: 95%; PHR: 5%); 72% with complete or partial molecular response | CHR: Hct <45% (men) and 42% (women), no phlebotomy, absence of splenomegaly, WBC (<10× 109/L) and platelet count (<400×109/L). PHR: Hct <45% (men) or 42% (women) but platelet count >400 ×109/L or persistent splenomegaly; >50% reduction of phlebotomy |
89% with any AE, 1 AE grade ≥3; 9 treatment discontinuations due to AE |
| Kiladjian et al.54 | 2018 | peg-IFN-α−2b 50–80 μg/day peg-IFN-α−2a 45–180 μg/day IFN-α−2a 3×106 IU/day IFN-α−2b 3×106 IU/day |
13 | ORR: 23% (CHR: 15%; PHR: 8%); no spleen response, no MPN-SAF symptom improvement | CHR: normalization of CBC withoutphlebotomy PHR: Hct <48% or 3% lower than baseline |
36 AE in 13 patients; 5 patients with AE grade ≥3; no treatment discontinuations due to AE |
| Kiladjian et al.54 | 2018 | peg-IFN-α−2b 25–50 μg/day peg-IFN-α−2a 45–135 μg/day IFN-α−2b 3–5×106 IU/day |
13 | ORR: 31% (CHR: 15%; PHR: 15%); no spleen response, no MPN-SAF symptom improvement | CHR: normalization of CBC without phlebotomy PHR: Hct <48% or 3% lower than baseline |
21 AE in 13 patients; 1 patient with AE grade ≥3; 1 treatment discontinuation due to AE |
| Kuriakose et al.60 | 2012 | rIFN-α−2b 0.5–3×106 IU t.i.w. peg-IFN-α−2a 15–225μg/week; dose adjustments based on efficacy and tolerance |
46 | ORR: 89% (CHR: 26%; PHR: 63%) | CHR: Hct <45% (men) or 42% (women), no phlebotomy, no splenomegaly, platelet count <600 ×109/L PHR: platelet count <600 ×109/L; >50% reduction of phlebotomy, persistent splenomegaly |
Not reported |
| Masarova et al.34 | 2017 | Peg-IFN-α−2a 90–450 μg/week | 43 | ORR: 84% (CHR: 77%; PHR: 7%) | Hematologic responsed based on 2009 ELN response criteria87 | 100% with any adverse event; 3 patients with transformation to AML or myelofibrosis |
| Ozturk et al.55 | 1997 | IFN-α−2b 3–10×106 IU t.i.w.; dose adjustments based on efficacy and tolerability | 7 | ORR: 100% (CHR: 86%; PHR: 14%) | CHR: Hct <45% without phlebotomy PHR: Hct 45–50% and >50% reduction in phlebotomy requirement |
100% with any AE, no grading provided, 1 treatment discontinuation due to AEs |
| Utke Rank et al.56 | 2016 | IFN-α−2b and peg-IFN-α−2b; dosing and schedule not specified | 9 | ORR: 100% (CHR: 67%; PR: 33%) | CHR: Hct <45% without phlebotomoy, normal WBC and platelet count, and resolution of symptoms and splenomegaly PR: Hct <45% or 3 other criteria |
Not reported |
| Radin et al.37 | 2003 | IFN-α2 2–5×106 IU/m2 daily; dose reductions based on adverse events | 12 | ORR: 42% (CR: 8%; PR: 33%); reduction in spleen size in 5 out of 7 patients, | CR: normalization of blood counts, normal blood smear, normal bone marrow, resolution of splenomegaly, no thrombotic or hemorrhagic events PR: any one of (1) Hb >10g/dL or (2) platelet count <800,000/mm3 without thrombotic or hemorrhagic events or (3) spleen size reduction >50% |
53 adverse events in 12 patients, 5 patients with ≥3 grade |
| Seewann et al.42 | 1991 | rIFN-α−2b 3–5×106 IU daily; maintenance treatement for up to 2 years with IFN 3–5×106 IU t.i.w. | 6 | ORR: 67% (CHR: 67%; PHR: 0%); 3 out of 3 patients free of phlebotomoy | CHR: platelet count <450,000/mm3 PHR: >50% reduction in platelet count |
Not reported |
| Stasi et al.57 | 1998 | Human leukocyte IFN-α 1.5–6×106 IU t.i.w. | 18 | ORR: 94% (CHR: 61%; PHR: 33%); 11 out of 18 patients free of phlebotomoy | CHR: Hct <45% withoutphlebotomies PHR: Hct 45–50% and >50% reduction in phlebotomy burden |
89% with flu-like symptoms; no treatment discontinuations due to AE |
| Stauffer Larsen et al.58 | 2009 | IFN-α−2b; dose and regimen not specified | 7 | ORR: 100% (CHR: 100%); all with major molecular response | CHR: normalization of blood counts without phlebotomies Major molecular response: JAK2 V617F VAF <0.2% |
Not reported |
| Taylor et al.59 | 1995 | rIFN-α−2a or rIFN-α−2b 3–8×106 IU t.i.w.; dose adjustments based efficacy and tolerability | 17 | ORR: 88% (CHR: 53%; PHR: 29%); 8 out of 9 patients with resolution of splenomegaly, freedom of phlebotomy not reported | CHR: Hct <45% without phlebotomies PHR: Hct 45–50% and >50% reduction in phlebotomy burden |
100% with flu-like symptoms; 6 treatment discontinuations due to AE |
| Turri et al.43 | 1991 | IFN-α−2a 3×106 IU daily; maintenance treatement for responding patients with IFN-α−2a 3×106 IU t.i.w. | 11 | ORR: 64% (CHR: 36%, PHR: 27%); 4 patients free of phlebotomy and reduction in spleen size | CHR: Hct <48% without need for phlebotomy PHR: reduction in phlebotomy requirements |
Not reported |
| 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 | 27 | ORR: 89% (CR: 67%, PR: 22%) | CR: normalization of blood counts, and resolution of splenomegaly PR: improvement in blood counts by >50% |
5 thromboembolic events, otherwise not reported |
AE – adverse events; AML – acute myeloid leukemia; CHR – complete hematologic response; CR – complete remission; ; ELN – European Leukemia Network; Hb – hemoglobin; Hct – Hematocrit; IFN - Interferon; IU - International units; IWG-MRT – International Working Group for Myeloproliferative Neoplasms Research and Treatment; MPN-SAF – myeloproliferative neoplasm symptom assessment form; ORR – overall response rate; PHR – partial hematologic response; PR – partial remission; rIFN – recombinant interferon; t.i.w. – three times per week; U – unit; VAF – variant allele frequency