CAR-T Therapy Go-ahead for Young Leukaemia Patients

Peter Russell

November 16, 2018

A cutting-edge treatment for some young people with a certain type of leukaemia won approval this week from the National Institute for Health and Care Excellence (NICE).

There were also drug safety updates from the Medicines and Healthcare products Regulatory Agency (MHRA) on hydrochlorothiazide-containing products, fluoroquinolones, and sildenafil.

Tisagenlecleucel for Young People with Leukaemia

Final draft guidance recommended CART-cell therapy via England's Cancer Drugs Fund for people aged between 3 and 25 with leukaemia.

NICE said that young people with relapsed or refractory B-cell acute lymphoblastic leukaemia (ALL) would now have access to tisagenlecleucel (Kymriah, Novartis).

The treatment involves taking a patient's own T cells and genetically modifying them to produce a protein called chimeric antigen receptor (CAR) that can attach to and kill cancer cells.

Tisagenlecleucel will be offered to people under the age of 25 who have not responded to current treatment, or who have relapsed after stem cell transplant.

It is estimated that around 25 to 30 people will be eligible for tisagenlecleucel each year in England.

A specialised NHS service is being developed to manage access to the new therapy. Novartis said it had been working alongside specialist hospitals to ensure training was in place.

The therapy, given as a single intravenous infusion, has a list price of £282,000, but the manufacturer agreed a discount for supply earlier this year.

Meindert Boysen, director of the Centre for Health Technology Evaluation at NICE said: "NICE’s recommendation of tisagenlecleucel marks a new generation of personalised medicine that has the potential to transform the care of patients with cancer worldwide."

Dr Alasdair Rankin, director of research at the blood cancer charity Bloodwise, said: "CART-cell therapy can give children with leukaemia the real possibility of long-term survival if they do not respond to standard treatments."

An appeal period will close on November 30th 2018.

Gemtuzumab Ozogamicin for Leukaemia

NICE recommended gemtuzumab ozogamicin (Mylotarg, Pfizer), with daunorubicin and cytarabine, as an option for people with untreated de novo CD33-positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia, in people aged 15 years and older.

Evidence from a randomised clinical trial showed that, for people whose disease had favourable or intermediate cytogenetics, gemtuzumab ozogamicin with daunorubicin and cytarabine was more clinically effective than daunorubicin and cytarabine.

Also, patients were more likely to live longer without the disease relapsing or symptoms returning.

Final guidance said use of the targeted therapy drug was dependent on:

  • Patients starting induction therapy when either the cytogenetic test confirms that the disease has favourable, intermediate or unknown cytogenetics (that is, because the test was unsuccessful), or when their cytogenetic test results are not yet available, and

  • Patients beginning consolidation therapy when their cytogenetic test confirms that the disease has favourable, intermediate or unknown cytogenetics (because the test was unsuccessful)

Its recommendation was also dependent on the manufacturer supplying the drug at an agreed, confidential discount to the £6300 per 5mg vial list price.

Warning Over Hydrochlorothiazide-Containing Products

Patients taking hydrochlorothiazide-containing products should be advised about the cumulative, dose-dependent risk of non-melanoma skin cancer, particularly in long-term use.

The MHRA said that studies have shown a dose-dependent increased risk of non-melanoma skin cancer (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC], including SCC lip cancer) with exposure to increasing cumulative doses of hydrochlorothiazide.

Doctors should advise patients regularly to check for and report any suspicious skin lesions or moles; to limit exposure to sunlight, and UV rays, and to use adequate sun protection, it said.

Fluoroquinolones and Aortic Aneurysm Risk

Patients at risk of aortic aneurysm and dissection, should only be given fluoroquinolones after careful assessment of the benefits and risks, and after consideration of other therapeutic options, the MHRA said.

It cautioned that studies had suggested an increased risk of aortic aneurysm and dissection with fluoroquinolone usage, particularly in older people.

Sildenafil and Persistent Pulmonary Hypertension

The MHRA said that sildenafil (Revatio and Viagra, Pfizer) was not authorised for use in pregnancy for the treatment of intrauterine growth restriction.

The STRIDER clinical trial, which was studying the use of sildenafil in pregnancy for intrauterine growth restriction, was prematurely discontinued due to a higher incidence of persistent pulmonary hypertension of the newborn, and neonatal mortality, in the sildenafil arm of the study.

Revatio for the treatment of pulmonary arterial hypertension was not recommended in pregnancy unless strictly necessary, the MHRA said, while Viagra was not authorised for use in women.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: