FIRST 2 CAR-T CELL PRODUCTS APPROVED IN EU

The first two T-cell therapies that use chimeric antigen receptor (CAR) technology have been recommended for marketing authorization today by the pivotal panel at the European Medicines Agency (EMA).

The agency's Committee for Medicinal Products for Human Use (CHMP) also recommended authorization of another hematologic cancer treatment and of a breast cancer drug that the panel had previously rejected.

But the endorsements of tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Kite Pharma), the two cutting-edge therapies for blood cancers, was the highlight of the panel's most recent meeting.

Tisagenlecleucel is recommended for use in pediatric and young adult patients (up to 25 years) with relapsed or refractory acute lymphoblastic leukemia. It is also indicated for treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

Axicabtagene ciloleucel is indicated for the treatment of adult patients with relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy.

Both agents are personalized cancer immunotherapies that are based on collecting and genetically modifying patients' own immune cells. They belong to a "new generation of personalized cancer immunotherapies," said the EMA in a press statement.

The main safety concerns with CAR T-cell therapy (CAR-T) are cytokine release syndrome (CRS), which is a systemic response involving high fever and flu-like symptoms, and neurologic toxicities. Both can be life-threatening and fatal. Monitoring and mitigation strategies for these adverse events are detailed in the product information and risk management plan. CRS can be treated successfully with tocilizumab (RoActemra, Roche); CHMP recommended having tocilizumab's indication extended for this use.

Other Decisions, Including Breast Cancer Drug Reversal

In addition to CAR-T, an orphan medicine for cancer was recommended by CHMP:daunorubicin/cytarabine (Vyxeos, Jazz Pharmaceuticals Ireland) for the treatment of acute myeloid leukemia (AML). The new agent is a liposomal formulation of a fixed combination of daunorubicin and cytarabine.

Compared with a standard combination of cytarabine and daunorubicin, the new formulation increased survival in patients with high-risk AML. The most common side effects are hypersensitivity (including rash), febrile neutropenia, edema, diarrhea/colitis, mucositis, fatigue, musculoskeletal pain, abdominal pain, decreased appetite, cough, headache, chills, arrhythmia, pyrexia, sleep disorders, and hypotension.

The CHMP also recommended granting a marketing authorization for neratinib (Nerlynx, Puma Biotechnology), for the adjuvant treatment of early-stage, hormone-receptor- and human epidermal growth factor receptor 2–positive breast cancer in patients who completed prior trastuzumab therapy. The decision was a reversal of CHMP's negative opinion in February 2018. The drug reduces the risk for disease recurrence after 2 years compared with placebo.

The most common side effects are diarrhea, nausea, fatigue, vomiting, abdominal pain, rash, decreased appetite, upper abdominal pain, stomatitis, and muscle spasms.

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