Cutaneous T Cell Lymphoma

Cutaneous T Cell Lymphoma

A disease in which certain cells of the lymph system (called T lymphocytes) become cancerous and affect the skin.

Zevalin® Effective for Treatment of Cutaneous B-Cell Lymphoma

Zevalin® (Yttrium-90 [(90)Y] ibritumomab tiuxetan) appears highly effective in the treatment of primary cutaneous B-cell lymphoma (PCBCL). The details of this study appeared in an early online publication in Leukemia-Lymphomaon July 25, 2008.

Non-Hodgkin’s lymphoma (NHL) is a form of cancer that begins in the cells of the lymph system. The lymph system includes the spleen, thymus, tonsils, bone marrow, lymph nodes, and circulating immune cells. The main cells in the lymph system are lymphocytes, of which there are two types: B and T-cells. Each of these cells has a specific function in helping the body to fight infection.

NHL is characterized by the excessive accumulation of atypical (cancerous) lymphocytes. These lymphocytes can crowd the lymph system and suppress the formation and function of other immune and blood cells. NHL is categorized by the type of lymphocyte it involves and by the rate at which the cancer grows. PCBCL is a type of NHL in which the immune cells of the skin are affected, creating “lesions,” or sores on the skin.

Standard therapies for PCBCL typically include chemotherapy and/or radiation therapy. However, researchers continue to evaluate novel therapeutic approaches that are both effective and reduce side effects.

Radioimmunotherapy is an approach that involves treatment with a radioactive substance linked to an antibody. The antibody attaches to cancer cells when injected into the body. By delivering the radiation directly to the cancer, a larger amount of normal tissue is spared from radiation and there are fewer side effects. Zevalin, a radioimmunotherapeutic agent, contains a monoclonal antibody portion that attaches to a protein (CD20) found only on the surface of B-lymphocytes, such as on cancerous B-cells found in many forms of NHL. The radioactivity that is spontaneously emitted targets the B-cell and destroys it.

Results from several clinical trials have demonstrated Zevalin’s effectiveness in the treatment of NHL. However, physicians must refer patients to radiologists or a nuclear medicine specialist for treatment with Zevalin. There is speculation that the referral process may contribute to low use of Zevalin among patients who might derive great benefit from its effects.

Researchers from Germany recently conducted a small clinical trial including 10 patients with PCBCL. All patients were treated with Zevalin.

  • 100% of patients achieved a complete disappearance of all detectable cancer (complete remission).
  • The median time to cancer progression was one year.
  • 40% of patients remain in complete remission at a median follow-up of 19 months.

The researchers concluded that these data provide further evidence that Zevalin appears extremely effective in several types of NHL, including PCBCL. Patients with PCBCL may wish to speak with their physician regarding their individual risks and benefits of treatment with Zevalin.

Vaccine Promising for Cutaneous T-Cell Lymphoma

According to a recent article published in the journal Blood, an immunotherapeutic vaccine may prove to be promising in the treatment of cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma is a type of Non-Hodgkin’s lymphoma (NHL). NHL is a form of cancer that begins in the cells of the lymph system. The lymph system includes the spleen, thymus, tonsils, bone marrow (spongy material inside large bones that produces blood cells), lymph nodes and circulating immune cells. The main cells in the lymph system are lymphocytes, of which there are two types: B and T-cells. Each of these cells has a very specific function in aiding the body to fight infection. NHL is characterized by the excessive accumulation of atypical (cancerous) lymphocytes. These lymphocytes can crowd the lymph system and suppress the formation and function of other immune and blood cells. Cutaneous T-cell lymphoma (CTCL) refers to the accumulation of cancerous T-cells in the skin. It is a rare type of cancer, with approximately 1,000 people in the United States diagnosed each year. CTCL is often a slowly progressive disease, initially causing dry patches of skin that may be itchy or painful. Eventually, CTCL can develop into solid masses in the skin that can spread to other organs.

Treatments for CTCL tend to be administered with intent to improve quality of life and duration of survival; rarely with intent to cure except for the possible exception of allogeneic stem cell transplantation. There are a variety of conventional chemotherapeutic agents which are modestly effective including the anthracyclines, alkylating agents, Pentostatin®, and Gemzar®. There are also a number of less common approaches that appear to have significant activity for the treatment of CTCL including extracorporeal photophoresis, denileukin diftitox, bexarotene, retinoids, and interleukin-12. However, these treatments usually result in incomplete anti-cancer responses lasting only three or more months. Researchers are continuing to evaluate different immunotherapeutic approaches, which stimulate the immune system to help fight the cancer, to improve survival for patients with CTCL.

Recently, researchers from Switzerland conducted a clinical trial utilizing vaccines for the treatment of CTCL. The vaccines were comprised from components of the patient’s own cancer cells, which were mixed with immune cells. The dendritic cells in the vaccine “presented” a small antigenic portion of the cancer cells to the immune system, in order to stimulate the patient’s immune cells to recognize the cancer cells in the body as foreign and mount an attack against them. This small trial involved 10 patients who received these injections, referred to as autologous tumor lysate pulsed dendritic cell vaccines. Half of the patients achieved an anti-cancer response following the vaccine, with 4 being partial anti-cancer responses and 1 achieving a complete disappearance of detectable cancer (complete response). Two patients who achieved a partial response experienced a continued response, while the other 2 had disease progression after 10 months. The patient who achieved a complete response had no disease recurrence at the time of publication of this trial. Overall, this treatment was reported to be well tolerated.

The researchers concluded that autologous tumor lysate pulsed dendritic cell vaccines may provide an active therapeutic approach in the treatment of CTCL, as standard treatment options do not provide impressive long-term outcomes. Future clinical trials evaluating this approach are warranted. Patients diagnosed with CTCL may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating vaccines of other promising therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (cancer.gov) and www.cancerconsultants.com. Personalized clinical trial searches are performed on behalf of patients at cancerconsultants.com.

Zolinza™ Approved for Cutaneous T-cell Lymphoma

The United States Food and Drug Administration (FDA) has approved Zolinza™ (vorinostat) for the treatment of patients with cutaneous (skin) T-cell lymphoma that has stopped responding to at least two previous systemic (full body) therapies.

Lymphoma is a type of cancer that originates in the immune system. T-cell lymphoma refers to lymphoma that originates in immune cells called T-cells. Cutaneous T-cell lymphoma (CTCL) is a type of T-cell lymphoma that affects the skin.

Two clinical studies evaluating Zolinza prompted its FDA approval. Patients in these studies had CTCL that had progressed or recurred following at least two prior therapies. They were treated with Zolinza.

  • 30% of patients experienced at least a 50% decrease in skin symptoms of CTCL for at least four weeks.
  • At least half were still responding to treatment at the time of analysis.
  • The most common side effects were fatigue, diarrhea, and nausea.

Patients with CTCL whose cancer has progressed despite treatment with prior therapies may wish to speak with their physician regarding their individual risks and benefits of treatment with Zolinza.

FDA Grants Full Approval of Ontak®

The United States Food and Drug Administration (FDA) has granted Eisai Pharmaceuticals full approval for their agent Ontak (denileukin diftitox). Ontak is now approved for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma whose cancer cells express the CD25 component of the IL-2 receptor.

Ontak consists of the sequence of interleukin-2 (IL-2) fused with a genetically engineered protein from a portion of the diptheria toxin. Ontak binds to the IL-2 portion of the malignant cell and delivers the diptheria toxin, resulting in cellular death.

The approval was prompted by a phase III trial directly comparing Ontak to placebo in patients with cutaneous T-cell lymphoma whose cancer cells expressed the CD25 component of the IL-2 receptor and who were resistant to other therapies.

Istodax Active against Refractory Cutaneous T-cell Lymphoma.

Final results from a Phase II clinical trial provide additional evidence that Istodax® (romidepsin) is active against refractory cutaneous T-cell lymphoma. These results were published in the Journal of Clinical Oncology.

Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin’s lymphoma that begins in the skin. The most common type of CTCL is mycosis fungoides.

Istodax—a histone deacetylase (HDAC) inhibitor—works by slowing the growth of cancer cells. It was approved in 2009 for the treatment of CTCL in patients who had received at least one prior systemic therapy.

The current report provides final results from one of the studies that contributed to the approval of Istodax. The study enrolled 96 patients with Stage IB to IVA CTCL who had received at least one prior systemic therapy. All patients were treated with Istodax on days 1, 8, and 15 of each 28-day cycle.

  • 34% of patients had a response to treatment (reduction or elimination of detectable lymphoma). Six patients had a complete response (no detectable lymphoma).
  • Among patients with advanced disease, 38% had a response to treatment. Five patients had a complete response.
  • The median time to response was two months, and the median duration of response was 15 months.
  • 43% of patients experienced an reduction in itching.
  • Side effects tended to be mild, and most commonly involved gastrointestinal disturbances and weakness or lack of energy.

These results provide additional evidence that Istodax is active against refractory CTCL, and generally well tolerated by patients.

Mogamulizumab Superior to Vorinostat in Cutaneous T Cell Lymphoma

Results were recently presented at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta from a international comparative clinical trail evaluating mogamulizumab in patients with previously treated cutaneous T-cell lymphoma (CTCL).

Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Because they are designed to specifically target cancer cells while leaving normal cells alone, targeted therapies usually have different, and sometimes milder, adverse side effects than standard chemotherapy drugs.

CTCL is a rare cancer of the white blood cells, specifically T lymphocytes, that primarily occurs in the skin. It is caused when T cells (cells in the immune system that help the body fight infection) begin to grow uncontrollably and build up in the skin. CTCL can also involve the blood, lymph nodes, and internal organs.

Mogamulizumab is a novel precision cancer medicine that is given intravenously and targets a protein (CCR4) that is frequently found on the surface of cancer cells in patients with CTCL. As a CCR4 antibody, the drug exploits the patient’s immune cells to attack the cancer.

In a head to head comparison the study found that the precision cancer medicine mogamulizumab improved progression-free survival, response rate, and quality of life compared to Zolinza™ (vorinostat), a U.S. Food and Drug Administration (FDA)-approved standard-of-care treatment for patients with CTCL. Mogamulizumab

Gemzar® Effective in Advanced Cutaneous T-Cell Lymphoma

According to a recent article published in the journal Cancer, treatment with the chemotherapy agent Gemzar® (gemcitabine) provides effective and well-tolerated therapy for patients with advanced cutaneous T-cell lymphoma.

Lymphoma refers to cancer that originates in the cells of the immune system. There are several different types of cells in the immune system from which lymphoma can arise; these various types of lymphomas are treated differently.

T-cell lymphoma refers to lymphoma that originates in immune cells called T-cells. Cutaneous T-cell lymphomas affect the skin; there are several subtypes of cutaneous T-cell lymphoma. Since options for treating advanced cutaneous T-cell lymphoma are limited, research continues into advancing therapeutic approaches for patients with this disease.

Researchers from Italy recently conducted a clinical trial to evaluate the effectiveness of Gemzar in the treatment of advanced cutaneous T-cell lymphoma. Gemzar has demonstrated anticancer activity in patients with cutaneous T-cell lymphoma that has stopped responding to previous therapies.

Researchers conducted this study with patients with advanced cutaneous T-cell lymphoma who had not undergone prior systemic (full body) therapy. This trial included 32 patients, the majority of whom had mycosis fungoides. Also included were patients with peripheral T-cell lymphoma with skin involvement and Sezary’s syndrome. Patients were treated with single-agent Gemzar.

  • An overall anticancer response was achieved in 75% of patients: Complete disappearance of detectable cancer was achieved in 22% of patients, and partial disappearance of cancer was achieved in 53% of patients.
  • Median progression-free survival was 10 months.
  • Median overall survival was 19 months.
  • Of the patients who had a complete disappearance of their cancer, nearly half of them had no disease progression at a median follow-up of 10 months.
  • Low levels of blood cells and conditions affecting the liver were the most common side effects; no patient died from treatment-related complications.

The researchers concluded that single agent Gemzar is well tolerated and appears active in the treatment of advanced cutaneous T-cell lymphoma as initial systemic therapy. A current study is underway evaluating Gemzar followed by Campath® (alemtuzumab) in this group of patients. Future clinical trials evaluating Gemzar in combination with other agents for the treatment of this disease are warranted.

Patients with advanced cutaneous T-cell lymphoma may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating novel therapeutic options. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.cancerconsultants.com .

Allogeneic Stem Cell Transplant Effective for Refractory Cutaneous Lymphoma

According to a recent article published in the Journal of Clinical Oncology, an allogeneic stem cell transplant appears effective in the treatment of cutaneous T-cell lymphomas that have stopped responding to standard therapies.

Lymphomas are a group of cancers that affect cells of the immune system, referred to as B-cells or T-cells. B-cell lymphomas are the most common and also receive more research attention. T-cell lymphomas tend to be more aggressive; when patients with T-cell lymphomas stop responding to standard therapies (refractory lymphoma), effective treatment options are limited.

An allogeneic stem cell transplant involves the use of high doses of chemotherapy, with or without radiation therapy, followed by an infusion of a donor’s stem cells. While the higher doses of therapy are used to kill more cancer cells than conventional doses, they also damage healthy cells and tissues. To replenish cells damaged during therapy, donor stem cells (immature blood cells) are collected prior to therapy and infused following therapy.

Even though an allogeneic stem cell transplant is associated with high rates of severe side effects, as well as mortality, it is often the only curative option in certain types of cancers. Researchers are now evaluating the use of more conventional doses of therapy prior to stem cell infusion, referred to as a non-myeloablative stem cell transplant. Anti-cancer effects are augmented with infusion of a donor’s stem cells: These cells often recognize the patient’s cancer cells as “foreign” and mount an attack against them. Unfortunately, they may also recognize a patient’s healthy tissues as foreign, resulting in a condition referred to as “graft-versus-host-disease”, or GVHD. Allogeneic stem cell transplant requires that a balance is maintained between producing a cure and keeping side effects acceptable.

Researchers from the City of Hope National Medical Center recently analyzed data from eight patients with cutaneous T-cell lymphomas, Sezary syndrome, and mycoses fungoides. These types of lymphomas affect the skin of patients. The data included patients who had stopped responding to several prior therapies. Four patients underwent an allogeneic stem cell transplant including high doses of therapy, and four underwent non-myeloablative allogeneic stem cell transplants.

All patients achieved a complete disappearance of detectable cancer. Two patients ultimately died from complications associated with treatment. At a follow-up of 56 months, the remaining six patients are alive and cancer-free. Patients treated with the non-myeloablative transplants suffered from fewer side effects.

The researchers concluded that allogeneic stem cell transplants result in long-term overall and cancer-free survivals in patients with refractory, cutaneous T-cell lymphomas. Patients with refractory, cutaneous T-cell lymphomas may wish to speak with their physician regarding their individual risks and benefits of undergoing an allogeneic stem cell transplant or the participation in a clinical trial further evaluating stem cell transplants or other promising therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.cancerconsultants.com .

FDA Approves New Treatment for Cutaneous T-Cell Lymphoma

The Food and Drug Administration (FDA) has recently approved a new drug called denileukin diftitox for the treatment of cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma is a type of Non-Hodgkin’s lymphoma (NHL). NHL is a form of cancer that begins in the cells of the lymph system. The lymph system includes the spleen, thymus, tonsils, bone marrow (spongy material inside large bones that produces blood cells), lymph nodes and circulating immune cells. The main cells in the lymph system are lymphocytes, of which there are two types: B and T-cells. Each of these cells has a very specific function in aiding the body to fight infection. NHL is characterized by the excessive accumulation of atypical (cancerous) lymphocytes. These lymphocytes can crowd the lymph system and suppress the formation and function of other immune and blood cells. Cutaneous T-cell lymphoma (CTCL) refers to the accumulation of cancerous T-cells in the skin. It is a rare type of cancer, with approximately 1,000 people in the United States diagnosed each year. CTCL is often a slowly progressive disease, initially causing dry patches of skin that may be itchy or painful. Eventually, CTCL can develop into solid masses in the skin that can spread to other organs.

Denileukin diftitox is a novel type of agent that is comprised of two separate proteins which have been fused together through laboratory processes. One of the proteins that make up denileukin diftitox is a poison (toxin) produced by the bacteria

Corynebacterium diphtheriae, commonly known as diphtheria. The other protein segment of denileukin diftitox is called interleukin-2 (IL-2), which is a naturally occurring immune protein responsible for stimulating T-cells. Denileukin diftitox produces anti-cancer responses by binding to cancerous T-cells. The IL-2 segment of denileukin diftitox binds to IL-2 receptors on cancerous T-cells, and then delivers the diphtheria toxin into the cancerous cell. Once inside, the toxin destroys the cell.

The pivotal clinical trial which prompted FDA approval for denileukin diftitox involved 71 patients with CTCL who were no longer responding to standard therapies. In this study, 30% of patients achieved a partial or complete disappearance of their cancer, for an average duration of 4 months following treatment with denileukin diftitox. The 10% of patients who achieved a complete disappearance of their cancer remained disease-free for an average of 9 months 1.

The approval of denileukin diftitox offers hope to patients with CTCL. Patients having CTCL that has stopped responding to standard treatments may wish to speak with their doctor about the risks and benefits of treatment with denileukin diftitox or the participation in a clinical trial evaluating other novel treatment strategies. Future clinical trials will be conducted to evaluate the implications of treatment with denileukin diftitox earlier in the disease course of CTCL. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov) and eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients.

Ontak Delays Progression of Patients with Cutaneous T-cell Lymphoma.

Among patients with cutaneous T-cell lymphoma, treatment with the drug Ontak® (denileukin diftitox) slows disease progression. These results were reported in the Journal of Clinical Oncology.

T-cell lymphoma, a type of non-Hodgkin’s lymphoma, originates in immune cells called T-cells. Cutaneous T-cell lymphoma (CTCL) is a type of T-cell lymphoma that affects the skin.

Ontak is a biologic agent that is approved for the treatment of cutaneous T-cell lymphoma. Ontak is comprised of two separate proteins: a toxin and interleukin-2 (IL-2), a protein produced by the immune system. The IL-2 segment of Ontak binds preferentially to CTCL cells and delivers the toxin into the cell. Once inside, the toxin destroys the cell.

This recent Phase III trial involved 144 patients with CTCL who had received up to three prior treatments. Participants were divided into three groups: those receiving 9 micrograms (lower dose) of Ontak; those receiving 18 micrograms (higher dose); and those receiving placebo. Ontak was delivered for five days at a rate of one infusion per day for up to eight courses every three weeks. Treatment was stopped if disease progressed or side effects were unacceptable.

  • Overall response rates were higher for the two groups receiving Ontak compared with the placebo group, with the highest response among patients receiving the higher dose: 49% for the higher-dose group, 38% for the lower-dose group, and 16% for the placebo group.
  • Risk of disease progression was reduced by 73% among patients in the higher-dose group compared with the placebo group, making progression-free survival longer among patients receiving Ontak.
  • Ontak was associated with more side effects than placebo, but, overall, severe side effects were relatively low.

The researchers concluded that Ontak extends progression-free survival and is relatively safe for patients with CTCL.

Reference: Mazza S, Gellrich S, Assaf C, et al. Yttrium-90 ibritumomab tiuxetan radioimmunotherapy in primary cutaneous B-cell lymphomas: first results of a prospective, monocentre study. Leukemia-Lymphoma[early online publication]. July 25, 2008.

Maier T, Tun-Kyi A, Tassis A, et al. Vaccination of Patients with Cutaneous T-Cell Lymphoma Using Intranodal Injection of Autologous Tumor-Lysate-Pulsed Dendritic Cells.

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Merck. FDA Approves Zolinza(TM), the First HDAC Inhibitor Approved for the Treatment of Cutaneous Manifestations in Patients with Cutaneous T-cell Lymphoma Who Have Tried and Failed Other Therapies. Available at: http://www.zolinza.com/zolinza/consumer/documents/zolinza_release.pdf. Accessed October 2006.

Whittaker SJ, Demierre M-F, Kim EJ et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. Journal of Clinical Oncology. Early online publication August 9, 2010.

Anti-CCR4 Monoclonal Antibody, Mogamulizumab, Demonstrates Significant Improvement in PFS Compared to Vorinostat in Patients with Previously Treated Cutaneous T-Cell Lymphoma (CTCL): Results from the Phase III MAVORIC Study [817]

Marchi E, Alinari L, Tani M, et al. Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients. Cancer. 2005;104:2437-2441.

Molina A, Zain J, Arber DA, et al. Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and Mycoses Fungoides. Journal of Clinical Oncology. 2005;23:6163-6171.

Journal of Clinical Oncology, Vol 19, No 2, pp 376-388, 2001

Prince HM, Duvic M, et al. Phase III Placebo-Controlled Trial of Denileukin Diftitox for Patients With Cutaneous T-Cell Lymphoma. Journal of Clinical Oncology [early online publication]. March 8, 2010.

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