Summary Safety Review - Cellex Photopheresis System and Venous Thromboembolism & Pulmonary Embolism

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2019-05-03

Product

Cellex Photopheresis System

Potential Safety Issue

Blood clots formed in a vein (Venous Thromboembolism, VTE) or in the lungs (Pulmonary Embolism, PE)

Key Messages

  • Cellex Photopheresis System (CPS) is a medical device used to treat the effects on skin of a type of cancer of the immune system (cutaneous T-cell lymphoma) which is not responding to other treatment. It is also used to treat systemic sclerosis.
  • Health Canada's review of the potential risk of blood clotting (thromboembolism) with the use of CPS followed a report by the United States Food and Drug Administration (US FDA) of 7 cases of thromboembolic events (2 of which involved death) in patients using CPS.
  • Health Canada's review concluded that the majority of the thromboembolic events reported worldwide happened after use of CPS to treat graft-versus-host-disease (GvHD), a condition which is not intended for treatment by CPS. GvHD is a disease where transplanted bone marrow or blood stem cells attack the body of the patient.
  • Health Canada has notified the manufacturer of CPS to update the device safety information (Instructions for Use) to add a warning that treatment of patients with GvHD is not an authorized intended use in Canada.

Overview

Cellex Photophoresis System (CPS) is a medical device licensed in Canada used to treat the effects on skin of a type of cancer of the immune system (cutaneous T-cell lymphoma) which is not responding to other treatment. It is also used to treat systemic sclerosis, a rare disease involving an abnormal response from the body's immune system that causes changes in the texture and appearance of the skin, and frequently involves the internal organs.

It is used in a process where the patient's blood is withdrawn and the white blood cells are separated out. The rest of the blood (red blood cells and plasma) is immediately returned to the patient's circulation. The white blood cells are exposed to ultraviolet-A (UVA) radiation in the presence of a light-activated drug (photoactive drug). The UVA radiation and photoactive drug activates the immune cells to enhance the patient's immune response. After irradiation, the white blood cells are also returned to the patient's circulation.

In early 2018, the US FDA announced they would assess the risk of venous thromboembolism (VTE) with the use of CPS. Venous thromboembolism (VTE) is a condition in which a blood clot forms in a vein. When VTE occurs in a deep vein (e.g., in a leg), it is called deep vein thrombosis (DVT). This type of blood clot can break away from the original site and travel to other parts of the body, blocking a blood vessel in other organs, such as the lungs, causing pulmonary embolism (PE). A thromboembolic event can include either a VTE or a PE.

The US FDA received 7 reports of VTE, including pulmonary embolism (PE), in patients using CPS, 2 of which involved death. In Canada, there were 29 incidents of side effects related to the use of CPS, and 1 of these cases reported a blood clotting incident.

Use in Canada

  • Cellex Photophoresis System (CPS) is a medical device licensed in Canada to treat the skin manifestation of a type of cancer of the immune system (cutaneous T-cell lymphoma) that is not responding to other treatment.
  • It is also used to treat systemic sclerosis.
  • CPS has been sold in Canada by the manufacturer Therakos since 2009.

Safety Review Findings

  • At the time of the review, Health Canada had received one report of an incident of blood clotting after using CPSa. Not enough information was provided in the report to clarify whether the use of CPS contributed to the cause of the blood clot.
  • Information given by the manufacturer of CPS, at Health Canada's request, identified 18 blood clotting (thromboembolic) events worldwide. In 8 of the 18 reports, the thromboembolic events happened within hours to 20 days after CPS treatment. Of the 18 events, 16 were thromboembolic incidents in patients being treated for graft-versus-host-disease (GvHD), which itself is a factor that increases risk for thromboembolic events. Treatment of GvHD is not an intended use of CPS. Additionally, 11 of the 18 reports had other risk factors for pulmonary embolism (PE) or deep vein thrombosis (DVT).
  • A search of the scientific literature did not find any articles related to the thromboembolic issue with CPS use or similar medical devices. There were some articles that focused on the role or effectiveness of treating blood cells with UVA light-activated drugs (photopheresis) in the treatment of GvHD.
  • A literature review by the manufacturer on the root cause of thromboembolic events after photophoresis treatment has identified several risk factors, including cancer-linked factors, cancer treatment (anti-neoplastic therapy) - linked factors, increased risk with using catheters in veins for a long period of time (dwelling venous catheters), GvHD, and previous thromboembolic events.

Conclusions and actions

  • Health Canada's review of the available information concluded that the majority of the thromboembolic events occurred after the use of CPS for the treatment of graft versus host disease (GvHD). Treatment of GvHD is not an intended use of CPS.
  • Considering the seriousness of the reported side effect with the off-label use of CPS, Health Canada has notified the manufacturer of CPS to update the device's Instructions for Use to include a warning that treatment of patients with GvHD is not an authorized use in Canada.
  • The manufacturer of CPS has notified customers of CPS of the risk of thromboembolic events when treating patients with GvHD.
  • If the manufacturer or industry associations require more information, they are encouraged to contact the Therapeutic Products Directorate.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this medical device both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

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