Blood cancers

Longer term data builds on new agents for polycythaemia vera


Ruxolitinib is a safe and effective long-term treatment option for patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea, research shows. 

A five-year follow-up of the RESPONSE trial, which randomised 342 patients to either the JAK 1 and 2 inhibitor or best available therapy, confirmed the initial primary response to ruxolitinib was durable with long-term therapy.

More than half (55%) of patients who achieved complete haematological remission in the primary analysis were still in remission after five years and the probability of maintaining overall clinicohaematological response was 67%.

By study completion, the majority of patients (65%) initially in the best available therapy arm had crossed over to ruxolitinib.

Many of these crossover patients did not require phlebotomy after 32 weeks of crossover.

The study also found no indication of any difference in adverse events between patients on the basis of duration of exposure to ruxolitinib.

Mild to moderate anaemia remained the most common adverse event.  

Rates of non-haematological adverse events were generally lower in the ruxolitinib group than the best available therapy group but included pruritus, diarrhoea and weight gain.

However the rates of non-melanoma skin cancer were higher in the patients originally assigned to ruxolitinib. 

The researchers concluded the treatment offers the first widely approved therapeutic alternative for a “post-hydroxyurea patient population.”

However a Comment article published in The Lancet Haematology, said ruxolitinib, like hydroxyurea, was a supportive therapy and should be compared with phlebotomy alone in treatment-naive patients before it could be considered a first line therapy.

“Finally, since polycythaemia vera arises in a haemopoietic stem cell and all current first line therapies are supportive, failure of any of these is an indication for the use of pegylated interferon, which specifically targets the involved haemopoietic stem cells.”

Meanwhile another longer term study in early polycythaemia vera has found ropeginterferon alfa-2b was more effective in inducing durable haematological responses and molecular remission than hydroxyurea.

The authors of the PROUD-PV study and its extension study CONTINUATION-PV said the novel pegylated interferon should now be considered a first-line cytoreductive therapy ahead of hydroxyurea.

The extension study found the proportion of patients with a complete haematological response was significantly higher in the ropeginterferon alfa-2b group than in the hydroxyurea group at both 24 months (71% v 49%) and 36 months (71% v 51%).

Molecular response rates – 68% v 33% at 24 months and 66% v 27% at 36 months – similarly favoured treatment with ropeginterferon alfa-2b.

The study found treatment-related adverse events, including serious adverse events, were similar in both groups.

“Our findings corroborate the disease-modifying potential of IFNα-based therapy that has consistently been shown in myeloproliferative neoplasms in several independent phase 2 studies.”

“The mechanism of action in polycythaemia vera is probably multimodal: selective exhaustion of haematopoietic stem cells carrying the oncogenic JAK2 mutation is proposed to be driven by differentiation, and the resulting sustained decrease in mutant JAK2 allele burden decreases genetic instability and the propensity to acquire secondary mutations which ultimately contribute to disease progression.”

However a Comment article still suggested caution.

“We do not have prospective data providing evidence of the potential to alter the natural course of these myeloproliferative neoplasms and this missing information is a fact that clinicians must acknowledge when discussing treatment approaches and therapeutic goals that matter to their patients.”

“Additionally, the tendency to envisage the administration of this active agent earlier in the disease course (ie, individuals at low risk and younger patients) is based on a broader concept of induction of functional cure associated with reduction in risk of disease progression and early death is not yet supported by prospective clinical trial data.”

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