Contributions
Type: Publication Only
Background
Targeted inhibitory therapy with first line BRAF-inhibitors has been used successfully in HCL patients refractory to or relapsing following previous lines of therapy, including cladribine and rituximab. Careful selection of eligible patients is mandatory since vemurafenib might cause secondary skin malignancies, photosensitivity, QTc-prolongation, liver enzyme elevations and arthralgia. Nevertheless, vemurafenib treatment has the advantage of perfect oral bioavailability, possibility of outpatient treatment, and the lack of hematological toxicity.
Aims
Treatment of relapsed/refractory hairy cell leukemia patients is a challenging task. We report on our experience gained with vemurafenib, a treatment option targeting the disease-defining genetic event, the BRAF V600E mutation.
Methods
Since 2012 January, six out of our 75 hairy cell leukemia patients were found to be refractory to at least two or three lines of therapy or relapsed repeatedly following previous treatments and thus were candidates for vemurafenib treatment. The National Institute for Quality and Organizational Development in Healthcare and Medicines permitted the off label use of vemurafenib in each case. All patients were male, median age was 67 yrs (40-83). One patient was refractory to four previous lines of therapy, the other patients relapsed, on average three times (2-6), and were ineligible for cladribine treatment (4/6 patients) or had cladribine-intolerance (1/6). Before starting vemurafenib, every patient underwent a dermato-oncological and ophtalmological screening. Treatment was planned for 56 days with 240 mg BID regime. Three-four months after treatment splenic ultrasound and bone marrow biopsy were performed to assess the response.
Results
Treatment lasted for 56 days, starting dosage was 240 mg BID. Three of six patients had no complaints during therapy. In two cases asymptomatic and reversible indirect hyperbilirubinaemy was detected without any other clinical signs of hemolysis of hepatic transaminase elevation. Dosage modification (240 mg once a day) was indicated in a patient with reversible grade 1 toxicoderma. In one case treatment was interrupted arbitrarily by the patient after 14 days because of grade 3 arthralgia. In another patient vemurafenib was withhold for 10 days because of community acquired pneumonia. Treatment responses were as follows: partial remission in 4/6, minor response 1/6, and still not evaluable in a recently treated patient A 83 year old patient received vemurafenib treatment for only 10 days when he had to be hospitalised due to progressive cardiac decompensation anaemia, renal insufficiency and hyperuricaemy . The patient died a few days later due to cardiac cause, an autopsy report was not available. Interestingly, in an 80-ys-old patient vemurafenib treatment resulted in gradual and stable normalisation of blood counts while the degree of bone marrow infiltration decreased from the initial 90% only to 70 % at three months after having finished therapy. With a median follow up time of 12 (1-22) months until now we observed no overt relapse in our HCL patients treated with vemurafenib.
Summary
Vemurafenib offers a feasible outpatient treatment option for relapsed/refractory patient without hematologic toxicity. Questions to be answered in prospective studies are the optimal dosage and duration of vemurafenib, retreatment and the possibility to combine treatment with a MEK inhibitor.
Keyword(s): Hairy cell leukemia, Refractory
Session topic: Publication Only
Type: Publication Only
Background
Targeted inhibitory therapy with first line BRAF-inhibitors has been used successfully in HCL patients refractory to or relapsing following previous lines of therapy, including cladribine and rituximab. Careful selection of eligible patients is mandatory since vemurafenib might cause secondary skin malignancies, photosensitivity, QTc-prolongation, liver enzyme elevations and arthralgia. Nevertheless, vemurafenib treatment has the advantage of perfect oral bioavailability, possibility of outpatient treatment, and the lack of hematological toxicity.
Aims
Treatment of relapsed/refractory hairy cell leukemia patients is a challenging task. We report on our experience gained with vemurafenib, a treatment option targeting the disease-defining genetic event, the BRAF V600E mutation.
Methods
Since 2012 January, six out of our 75 hairy cell leukemia patients were found to be refractory to at least two or three lines of therapy or relapsed repeatedly following previous treatments and thus were candidates for vemurafenib treatment. The National Institute for Quality and Organizational Development in Healthcare and Medicines permitted the off label use of vemurafenib in each case. All patients were male, median age was 67 yrs (40-83). One patient was refractory to four previous lines of therapy, the other patients relapsed, on average three times (2-6), and were ineligible for cladribine treatment (4/6 patients) or had cladribine-intolerance (1/6). Before starting vemurafenib, every patient underwent a dermato-oncological and ophtalmological screening. Treatment was planned for 56 days with 240 mg BID regime. Three-four months after treatment splenic ultrasound and bone marrow biopsy were performed to assess the response.
Results
Treatment lasted for 56 days, starting dosage was 240 mg BID. Three of six patients had no complaints during therapy. In two cases asymptomatic and reversible indirect hyperbilirubinaemy was detected without any other clinical signs of hemolysis of hepatic transaminase elevation. Dosage modification (240 mg once a day) was indicated in a patient with reversible grade 1 toxicoderma. In one case treatment was interrupted arbitrarily by the patient after 14 days because of grade 3 arthralgia. In another patient vemurafenib was withhold for 10 days because of community acquired pneumonia. Treatment responses were as follows: partial remission in 4/6, minor response 1/6, and still not evaluable in a recently treated patient A 83 year old patient received vemurafenib treatment for only 10 days when he had to be hospitalised due to progressive cardiac decompensation anaemia, renal insufficiency and hyperuricaemy . The patient died a few days later due to cardiac cause, an autopsy report was not available. Interestingly, in an 80-ys-old patient vemurafenib treatment resulted in gradual and stable normalisation of blood counts while the degree of bone marrow infiltration decreased from the initial 90% only to 70 % at three months after having finished therapy. With a median follow up time of 12 (1-22) months until now we observed no overt relapse in our HCL patients treated with vemurafenib.
Summary
Vemurafenib offers a feasible outpatient treatment option for relapsed/refractory patient without hematologic toxicity. Questions to be answered in prospective studies are the optimal dosage and duration of vemurafenib, retreatment and the possibility to combine treatment with a MEK inhibitor.
Keyword(s): Hairy cell leukemia, Refractory
Session topic: Publication Only