Vemurafenib ‘Effective’ For Refractory, Relapsed Hairy-Cell Leukaemia

Vemurafenib may offer novel treatment option for hairy-cell leukaemia patients

medwireNews: The oral BRAF inhibitor vemurafenib shows promise for the treatment of patients with hairy-cell leukaemia that has relapsed or is refractory to purine analogue therapy, suggest results from two phase II clinical trials.

Vemurafenib 960 mg twice daily was administered for a median of 16 weeks to 26 patients in an Italian study, which had a median follow-up of 2 years, and for a median of 18 weeks to the first 24 patients enrolled in an ongoing US study.

Responses were recorded for 96% of the Italian participants, with 35% achieving a complete response and 62% a partial response after a median of 8 weeks, report Brunangelo Falini, from the University of Perugia in Italy, and co-investigators.

Patient platelet and neutrophil counts recovered in Italian patients after a median of 2 and 4 weeks, respectively, and haemoglobin level after a median of 8 weeks. Symptomatic splenomegaly reversion and clearance of leukaemia cells from circulation occurred within 2 weeks. And measurement of bone marrow infiltration after 4 weeks of treatment showed a “substantial decrease”.

Similarly, 42% of US patients had a complete response and 58% a partial response after 12 weeks of vemurafenib treatment, with most participants achieving neutrophil, platelet and haemoglobin recovery by 28 days.

Analysis of response duration in the Italian trial gave a median relapse-free survival of 9 months but this was significantly longer in patients with a complete than partial response, at 19 versus 6 months, respectively. Median treatment-free survival was 21.5 months in the 26 evaluated patients.

Five patients remained relapse-free at the last assessment, 23 to 25 months after completing treatment, the authors report in The New England Journal of Medicine.

At time of data cutoff in the US trial, median follow-up was 11.7 months and the 1-year rates for progression-free and overall survival were 73% and 91%, respectively.

Vemurafenib-related adverse events were “manageable” and comparable to those seen in patients treated with the drug for melanoma – described as reversible, mainly grade 1 or 2, and most commonly rash, photosensitivity, arthralgia or arthritis, pyrexia and elevated bilirubin.

Two Italian patients and three US patients developed cutaneous basal cell carcinoma, while one patient in each population developed cutaneous superficial melanoma; the majority of these patients had a history of skin cancer.

The researchers observe that they limited vemurafenib treatment duration because of concerns over secondary tumours. “Although such tumors affect primarily the skin and are of low malignant potential, their development may be less acceptable in patients with an indolent leukemia (however refractory or multiply relapsed) than in those with metastatic melanoma”, they note.

Nevertheless, the researchers write: “The absence of clinically significant myelotoxic effects makes vemurafenib an ideal salvage treatment for patients with multiply relapsed hairy-cell leukemia who have pancytopenia and scarce bone marrow reserve owing to previous chemotherapies.”

Finally, the team reports that treatment response in the patients was associated with undetectable levels of ERK expression in residual hairy cells in bone marrow biopsy, while persistent expression was associated with residual disease and shorter progression-free survival, indicating that “reactivation of MEK and ERK is a resistance mechanism to vemurafenib”.

This “establishes a rationale for combined BRAF and MEK blockade, which has been used successfully in patients with metastatic melanoma”, they conclude.


Tiacci E, Park JH, De Carolis L, et al. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med 2015; Advance online publication 9 September. DOI:  10.1056/NEJMoa1506583

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