Photopheresis Process Offers Relief From Lymphoma Lesions: An Interview With Dennis Parenti, MD

Dennis Parenti, MD, vice president of Clinical Affairs for Therakos

In addition to the danger they pose, the cancerous red patches, plaques, and tumors that arise from cutaneous T-cell lymphoma (CTCL) represent an enormous quality-of-life issue for patients.

When it comes to alleviating the lesions caused by this group of non-Hodgkin lymphomas—in which malignant CD4- positive lymphocytes proliferate and infiltrate the skin—doctors can prescribe a number of therapies. The lesions can be treated topically, with retinoids and phototherapy, or with systemic therapies.

There’s also another option: Therakos photopheresis is indicated for the palliative treatment of skin manifestations of CTCL that are unresponsive to other therapies. The technique is intended to reduce redness, itching, and the size of the lesions; in some cases, it entirely clears the skin.

Headquartered in Raritan, New Jersey, Therakos is a division of Ortho Clinical Diagnostics, part of the Johnson & Johnson family of companies. Its first photopheresis machine became available in 1988, and since then the company’s technique for extracorporeal photopheresis (ECP) has been used in more than 700,000 treatments.

Therakos photopheresis has demonstrated efficacy and safety in CTCL patients, and has not been associated with secondary malignancies or opportunistic infections, according to a 1987 study and the company’s own data.¹

To learn more about how photopheresis can help patients fight the symptoms of CTCL, OncologyLive spoke with Dennis Parenti, MD, vice president of Clinical Affairs for Therakos.

OncologyLive: What is extracorporeal photopheresis?

Parenti: ECP is an immune modulation therapy that was approved by the FDA for the palliative treatment of the skin manifestations of CTCL. ECP is also known as photoimmune therapy or immune cell therapy, and works by using either the integrated Therakos Uvar XTS or Cellex photopheresis systems to collect a small amount of whole blood from a patient connected to the system.

The system then separates the white blood cells; treats them with an exvivo methoxsalen (8-MOP) sterile solution, a photoactivable substance; activates the methoxsalen by UVA light; and reinfuses the white cells back into the patient. The treated white cells will start to undergo normal programmed cell death (apoptosis), which triggers a cascade of immunologic events. Less than 10% of all white cells are treated, yet some patients achieve a complete improvement in symptoms.

Please explain more extensively the impact that ECP has on the immune system.

Although the exact mechanism of action is not known, photopheresis may activate the immune-mediated response to modulate malignant T lymphocytes. ECP helps to restore the body’s natural ability to maintain a balanced immune system by controlling the activity of overactive immune cells. Healthy immune systems maintain a balance between the effector cells that fight infection and the regulatory cells that prevent immune-mediated diseases like CTCL. Other therapies for restoring a balanced immune system have traditionally targeted the effector cells by suppressing their function, thus suppressing the immune system. However, ECP is believed to boost the number of the regulatory cells (T-regs) of the immune system, providing a novel approach that may have significant activity in the treatment of disease, including skin manifestations, without inducing generalized immunosuppression.

Therakos Cellex

Photopheresis System

Why do patients need multiple treatments? What parameters do you use to determine when patients can stop treatment?

Patients receiving Therakos photopheresis may not see results right away. Patients are typically treated on two consecutive days each month for several months. If that doesn’t result in an improvement in skin findings, treatment can be accelerated to two consecutive days every two weeks for three months. If a response is maintained, the frequency of treatments can be gradually diminished or stopped. If the program of therapy has not stimulated an improvement after 20 treatments, healthcare practitioners should use their judgment in determining whether to continue.²

How are some of the adverse events with this technology managed?

Risks associated with ECP therapy include hypotension, fever, or worsening erythema, which usually resolves itself in one day. Physicians should advise ECP recipients to take precautions to avoid certain side effects of methoxsalen treatment. For instance, for 24 hours after treatment, a patient’s skin is extremely photosensitive. During this time, patients should be advised to avoid going outdoors and to cover up as much of their bodies as possible if they have to go out, including wearing sunglasses and hats for extra protection.

Please discuss the studies and results that Therakos presented to the FDA in seeking approval for its photopheresis systems.

The safety and efficacy of ECP using Therakos systems is well documented. The FDA approval of Therakos technology to treat the skin manifestations of CTCL that are not responsive to other therapies was obtained in 1987 based on a study done by Richard Edelson, MD, and others,³ which was conducted using oral methoxsalen followed by the extracorporeal exposure of a leukocyte-rich blood fraction to ultraviolet A; the blood was then returned to the patients. In that study, published in The New England Journal of Medicine, 54% of patients had a response within six months of the initiation of treatment. The study that served as the basis of approval for the Cellex instrument⁴ was published by Emil Bisaccia, MD, and his colleagues in the British Journal of Dermatology in 2009.

Is Therakos pursuing applications for ECP in conditions besides CTCL?

On December 6, 2011, Therakos announced that the first patient had been enrolled in its phase IIB clinical study⁵ evaluating the use of the company’s photopheresis technology in the treatment of patients with moderate to severe chronic graft-versus-host disease (GVHD). An estimated 15,000 new patients worldwide are diagnosed every year with chronic GVHD, which can be a life-threatening complication of allogeneic bone marrow transplantation.

The Therakos study will assess the safety and efficacy of ECP as an add-on to the standard of care for patients suffering from moderate to severe GVHD. Patients will be enrolled over an 18-month period. Randomization will occur in a 1:1 ratio, with half the patients receiving the current standard of care (systemic corticosteroids and cyclosporine) and the other half receiving standard of care coupled with ECP.

1. Blood is drawn and separated via centrifugation; leukocyte (white blood cell) enriched Buffy Coat isolated and collected
2. Plasma and red blood cells immediately returned to patient
3. Methoxsalen (20 micrograms / mL) added to Buffy Coat
4. Buffy Coat exposed to UVA light
5. Photoactivated Buffy Coat returned to patient

Therakos’ photopheresis procedure is a five-step process.

Illustration courtesy of Therakos, Inc

Please tell us more about Therakos photopheresis systems.

The Therakos Uvar XTS and Therakos Cellex photopheresis systems are the only integrated, regulatory-approved ECP devices. The Therakos Uvar was the first-generation system, and was later replaced by the Therakos Uvar XTS photopheresis system.

The Uvar XTS utilizes a modular design that minimizes setup time, reduces waste, and is patient-focused—all without altering the science of the therapy or its effect on the patient. It requires approximately three hours of treatment time to complete patient therapy. The extracorporeal volume (ECV) will vary depending on the size of the bowl that is required.

In 2009, the next-generation Therakos Cellex photopheresis system was launched. It incorporates innovative and advanced technologies, providing a new level of patient-focused care, and was designed in response to physician feedback. It is a single, integrated, closed system with the same reduced risk of infection, cross-contamination, and reinfusion errors as the Therakos Uvar XTS system, but allows for single-operator management. It has shorter treatment times (halved from 3 hours to 1.5 hours), reduced extracorporeal blood volume versus the previous model, and new separation technology. In the study done by Dr. Bisaccia, the mean time for a single-needle procedure was 103 minutes, and for a double-needle procedure was 74 minutes. The ECV will vary depending on whether a single- or double-needle procedure is used.

What skills and training are needed to operate the systems? How difficult are they to operate? How many patients can one system handle?

The therapy should only be prescribed by healthcare practitioners familiar with this treatment and trained to properly administer it. Therakos provides that training, determining how much instruction is required at a site based upon the operator’s previous experience. For example, someone who has worked in a blood bank on apheresis instrumentation or in dialysis will require a few days of pretraining background reading and several days of hands-on basic training. A technician with other healthcare experience can be trained in nearly the same amount of time. Therakos also provides more advanced levels of training on an as-needed basis. It is offered in centers that treat patients who are facing challenging medical conditions such as low body weight or elevated bilirubin.

Can this system be used by community-based oncologists, or is it primarily used in large cancer centers?

The procedure may be performed in hospitals, blood banks, or large community cancer centers.

References

1. THERAKOS™ photopheresis: more than 500,000 treatments given. Therakos website. http://www.therakos.com/healthcare-professionals/photopheresis. Accessed April 23, 2012.
2. Photopheresis treatment/non-Hodgkin’s lymphoma. Therakos website. http://www.therakos.com/healthcare-professionals/photopheresis/about-photopheresis. Accessed April 23, 2012.
3. Edelson R, Berger C, Gasparro F, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. N Engl J of Med. 1987; 316(6): 297-303.
4. Bisaccia E, Vonderheid EC, Geskin L. Safety of a new, single, integrated, closed photopheresis system in patients with cutaneous T-cell lymphoma [published online ahead of print March 9, 2009]. Br J Dermatol. 2009;161(1):167-169. doi: 10.1111/j.1365-2133.2009.09081.x.
5. US National Institutes of Health. A safety and efficacy study of Uvadex and extracorporeal photopheresis (ECP) in chronic graft versus host disease. ClinicalTrials.gov website. http://www.clinicaltrials.gov/ct2/show/NCT01380535?term=therakos&rank=6. Published June 22, 2011. Updated March 14, 2012. Accessed April 23, 2012.