Novartis PV Nanomodules

Prescribing information (hosted externally)

Second- or later‑line treatment options for polycythaemia vera

JAKAVI^® (ruxolitinib)

Oral inhibitor of the JAK1 and JAK2 tyrosine kinases¹
Blocks JAK/STAT signalling pathway, regulating activation of genes that promote cell survival and proliferation¹
Indicated for patients with PV who are resistant to or intolerant of hydroxyurea¹
The most frequently reported adverse drug reactions were anaemia and increased alanine aminotransferase.¹ Further information

Summary of efficacy data from RESPONSE and RESPONSE‑2 trials

Consult the JAKAVI Summary of Product Characteristics for further information.

Anagrelide

Anagrelide is an antiplatelet and cytoreductive therapy that can reduce the rate of platelet formation in bone marrow without affecting other blood cells⁵
Recommended by ELN for the second-line treatment of essential thrombocythaemia⁶
Not approved,⁷ but occasionally used in PV management⁸
Adverse events include headaches, nausea, diarrhoea, dizziness, fluid retention, and heart and blood-pressure problems, including arterial thrombosis^5,7-9
Tolerability profile may limit use in PV⁸

Busulphan

Busulphan is a non-specific alkylating agent⁹
ELN guidance recommends that busulphan may be considered second line in very elderly patients¹⁰
Offers durable haematologic control in PV at low doses⁹
Potentially leukaemogenic, although risk lower at low dose⁹
Sequential use of busulphan after HU resulted in an increased risk of secondary malignancies, including leukaemias^9,11

Anagrelide and busulphan are not indicated for the treatment of PV.^7,12

Example patient profiles

Ravi, 52 years

Diagnosed with PV 2 years ago
Intolerant to HU
High JAK2 V617F allele burden
Need for frequent phlebotomy
Absence of symptomatic splenomegaly

Ravi's second-line treatment

Ropeginterferon alfa‑2b

Ropeginterferon alfa-2b may be a suitable option for Ravi; it is indicated as monotherapy in adults with PV without symptomatic splenomegaly.¹³

Ropeginterferon alfa-2b is recommended as a substitute for first-line HU¹⁰ and has been shown to provide sustained reductions in mutation burden of JAK2 V617F versus baseline.¹³

Mary, 68 years

Diagnosed with PV 5 years ago
Resistant to HU treatment
Persisting symptoms of splenomegaly and high platelet count

Mary's second-line treatment

JAKAVI^® (ruxolitinib)

Mary has high-risk PV and is resistant to HU, meaning JAKAVI^® is a potential treatment option for her.¹ JAKAVI^® has demonstrated efficacy for splenomegaly and HCT levels.^1-3 See more

Busulphan would not be considered in this context because Mary is aged <80 years, meaning probability of secondary malignancy may pose an unacceptable risk.^9,11

Treatment of PV may be continued as long as the benefit-risk remains positive. However, the treatment should be discontinued after 6 months if there has been no reduction in spleen size or improvement in symptoms since initiation of therapy.¹

It is recommended that, for patients who have demonstrated some degree of clinical improvement, ruxolitinib therapy be discontinued if they sustain an increase in their spleen length of 40% compared with baseline size (roughly equivalent to a 25% increase in spleen volume) and no longer have tangible improvement in disease-related symptoms.¹

NEXT: BSH guidelines for high-risk patients with PV

BSH: British Society for Haematology; CV: cardiovascular; ELN: European LeukemiaNet; HCT: haematocrit; HU: hydroxyurea; IFN: interferon; JAK/STAT: Janus kinase/ signal transducer and activator of transcription; PV: polycythaemia vera; WBC: white blood cell

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JAKAVI^® (ruxolitinib) is indicated for the treatment of adult patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea.¹

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report or alternatively email medinfo.uk@novartis.com or call 01276 698370.

References

JAKAVI^® Summary of Product Characteristics. Available at: www.medicines.org.uk (for GB) or www.emcmedicines.com (for NI). Accessed November 2024
Vannucchi A M, Kiladjian J J et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 2015;372(5):426-435
Griesshammer M, Saydam G et al. Ruxolitinib for the treatment of inadequately controlled polycythemia vera without splenomegaly: 80-week follow-up from the RESPONSE-2 trial. Ann Hematol 2018;97(9):1591-1600
Passamonti F, Griesshammer M et al. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol 2017;18(1):88-99
Leukemia and Lymphoma Society. Polycythemia vera facts. Available at: lls.org. Accessed November 2024
Barbui T, Barosi G et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 2011;29(6):761-770
Anagrelide hydrochloride Summary of Product Characteristics
Rippel N, Tremblay D et al. Anagrelide for platelet-directed cytoreduction in polycythemia vera: Insights into utility and safety outcomes from a large multi-center database. Leuk Res 2022;119:106903
Barbui T, Finazzi M C, Finazzi G. Front-line therapy in polycythemia vera and essential thrombocythemia. Blood Rev 2012;26(5):205-211
Barbui T, Tefferi A et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 2018;32(5):1057-1069
Sever M, Newberry K J, Verstovsek S. Therapeutic options for patients with polycythemia vera and essential thrombocythemia refractory/resistant to hydroxyurea. Leuk Lymphoma 2014;55(12):2685-2690
Busulphan Summary of Product Characteristics
Ropeginterferon alfa-2b Summary of Product Characteristics
McMullin M F, Harrison C N et al. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology Guideline. Br J Haematol 2019;184(2):176-191

RESPONSE was a phase III, randomised, open-label, multicentre trial to evaluate the efficacy and safety of JAKAVI^® (n=110) versus best available therapy (n=112). The primary endpoint was HCT control and ≥35% reduction in spleen volume at Week 32. The trial included venesection-dependent patients with splenomegaly, who had hydroxyurea (HU)‑resistant or -intolerant PV.²

HCT control* and ≥35% reductions in spleen volume at Week 32²	JAKAVI^®	Best available therapy
	21%	1%
	p<0.001

Initial standard therapy included hydroxyurea (58.9%), interferon (11.6%), anagrelide (7.1%), immunomodulators (4.5%), and pipobroman (1.8%); no medication was administered in 15.2% of the patients.²

RESPONSE‑2 was a phase IIIb, prospective, randomised, open-label, multicentre trial to assess the efficacy and safety of JAKAVI^® (n=74) versus best available therapy (n=75). The primary endpoint was the proportion of patients who achieved HCT control at Week 28. The trial included venesection-dependent patients with PV without splenomegaly who are resistant to or intolerant of HU.³

HCT control* at Week 28⁴	JAKAVI^®	Best available therapy
	62%	19%
	p<0.0001
Total number of venesections (up to Week 80)³	JAKAVI^®	Best available therapy
Total number of venesections (up to Week 80)³	36	106

*Control was defined as no venesection eligibility (defined as HCT of >45% and ≥3% percentage points above baseline or HCT >48%).^2,3

HCT: haematocrit

References: 2. Vannucchi A M et al. N Engl J Med 2015;372:426-435; 3. Griesshammer M et al. Ann Hematol 2018;97:1591-1600; 4. Passamonti F et al. Lancet Oncol 2017;18:88-99

Prescribing information and adverse event reporting (hosted externally) ›

The treatment landscape for polycythaemia vera

Second- or later‑line treatment options for polycythaemia vera

JAKAVI® (ruxolitinib)

Anagrelide

Busulphan

Anagrelide and busulphan are not indicated for the treatment of PV.7,12

Example patient profiles

Ravi, 52 years

Ropeginterferon alfa‑2b

Mary, 68 years

JAKAVI® (ruxolitinib)

References

The treatment landscape
for polycythaemia vera

JAKAVI^® (ruxolitinib)

Anagrelide and busulphan are not indicated for the treatment of PV.^7,12

JAKAVI^® (ruxolitinib)