Cutaneous T-Cell Lymphoma - Market Insight, Epidemiology and Market Forecast - 2034

Key Highlights

• Lymphomas are cancers that originate in the lymphatic system, specifically from a type of white blood cell called a lymphocyte.Lymphocytes can be further sub-divided into B cells, T cells and NK cells.
• Lymphomas are broadly divided into two major categories: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). When NHL begins in the skin (not in another part of the lymphatic system such as the lymph nodes, organs, or lymph tissue) it is called a cutaneous (skin) lymphoma. B-cell lymphomas have a higher incidence than T-cell lymphomas except in the skin.
• Cutaneous T-cell lymphomas (CTCL) are rare cancers that primarily affect the skin, with some types growing slowly in the skin and others spreading to the blood or lymph nodes.
• The most common type of CTCL is mycosis fungoides and its leukemic variant, Sezary syndrome. The other more commonly seen forms of cutaneous lymphoma include the CD30 positive lymphoproliferative disorders (CD30+ LPDs).
• The signs and symptoms of CTCL vary depending on the type. Symptoms of CTCL encompass dry, red, scaly patches or bumps, rashes, lesions, and tumors on the skin, often accompanied by enlarged lymph nodes.
• Medical history, physical examination, biopsy of a skin tumor or lymph node is used to confirm the diagnosis. Additional imaging testing with PET and/or CT scanning may be required to evaluate internal involvement.
• In 2023, the United States accounted for the highest number of incident cases of CTCL in the 7MM.
• In the United States, males accounted for the higher number of incident population of CTCL in 2023. As per the report, these cases are projected to increase by 2034.
• Among the EU4 and the UK, out of all stage-specific cases of CTCL, 1,406 cases were of Stage IA, whereas, Stage IVB comprised of 41 cases in 2023.
• Treatments that work on the skin to treat CTCL include VALCHLOR (mechlorethamine), corticosteroids, light therapy, radiation therapy, and others. The treatment that works throughout the body is POTELIGEO (mogamulizumab), ADCETRIS (brentuximab vedotin), and others.
• In the 7MM, the United States accounted for the highest market size, with nearly 70% of the market share of the CTCL market as compared to EU4 and the UK and Japan in 2023.
• In 2023, among EU4 and the UK, Germany accounted for the largest market size, while Spain accounted for the smallest share.
• Emerging therapies in the pipeline, including SGX301 and I/ONTAK (E7777), are expected to bring a positive shift in the CTCL treatment landscape during the forecast period (2024-2034).
• With the upcoming therapies coming for CTCL, the market size is expected to increase, giving the patient population some drugs that can act as standard care for the patients. Major emerging key players include SGX301 (Soligenix), I/ONTAK (Citius Pharma), Lacutamab (Innate Pharma), KINSELBY (4SC AG) and others.
• Clinicians treating CTCL express a pressing need for more treatment options with reduced side effects indicating dissatisfaction with current therapies. Notably, there is currently no approved first-line therapy for early stage (I-IIA) CTCL, highlighting a significant unmet need in this patient population.

Report Summary

• The report offers extensive knowledge regarding the epidemiology segments (by region, total incident population of CTCL, type-specific cases, gender-specific cases, stage-specific cases, and line-specific cases) and predictions, presenting a deep understanding of the potential future growth in diagnosis rates, disease progression, and treatment guidelines. It provides comprehensive insights into these aspects, enabling a thorough assessment of the subject matter.
• Additionally, an all-inclusive account of the current management techniques and emerging therapies such as SGX301, I/ONTAK (E7777) and the elaborative profiles of late and mid-stage (Phase III and Phase II) and prominent therapies that would impact the current treatment landscape and result in an overall market shift has been provided in the report.
• The report also encompasses a comprehensive analysis of the CTCL market, providing an in-depth examination of its historical and projected market size (2020-2034). It also includes the market share of therapies, detailed assumptions, and the underlying rationale for our methodology. The report also includes drug outreach coverage in the 7MM region.
• The report includes qualitative insights that provide an edge while developing business strategies by understanding trends through SWOT analysis and expert insights/KOL views, including experts from various hospitals and prominent universities, patient journey, and treatment preferences that help shape and drive the 7MM CTCL market.

Market

Various key players, such as Soligenix, 4SC AG, Innate Pharma and others, are involved in developing therapies for CTCL. The expected launch of emerging therapies and other treatments will lead to a significant increase in the market size during the forecast period [2024-2034].

• In 2023, the total market size of CTCL was around USD 520 million, which is expected to increase by 2034 during the study period (2020-2034) in the 7MM.
• Among the 7MM, the United States accounted for the highest market size in 2023, followed by Japan for CTCL.
• During the forecast period (2024-2034), pipeline candidates such as SGX301, I/ONTAK (E7777) and Lacutamab (IPH4102) are expected to drive the rise in CTCL market size.
• By 2034, Poteligeo (mogamulizumab) is expected to garner the largest market share in the 7MM.

CTCL Drug Chapters

The section dedicated to drugs in the CTCL report provides an in-depth evaluation of pipeline drugs (Phase III and Phase II) related to CTCL.

The drug chapters section provides valuable information on various aspects related to clinical trials of CTCL, such as the pharmacological mechanisms of the drugs involved, designations, approval status, patent information, and a comprehensive analysis of the pros and cons associated with each drug. Furthermore, it presents the most recent news updates and press releases on drugs targeting CTCL.

Marketed Therapies

ADCETRIS (brentuximab vedotin): Pfizer (Seagen)
ADCETRIS (brentuximab vedotin) is a CD30-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Brentuximab vedotin is an antibody-drug conjugate (ADC); the antibody is a chimeric IgG1 directed against CD30. The small molecule MMAE is a microtubule-disrupting agent; MMAE is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of ADCETRIS is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC-CD30 complex and the release of MMAE via proteolytic cleavage. The binding of MMAE to tubulin disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptotic death of the cells. Additionally, in vitro data provide evidence for antibody-dependent cellular phagocytosis (ADCP).

Seattle Genetics (Seagen) and Takeda jointly developed ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. In December 2023, Pfizer announced the successful completion of its acquisition of Seagen.

Emerging Therapies

HYBRYTE (SGX301): Soligenix

HyBryte (synthetic hypericin or SGX301) is a photodynamic therapy using synthetically manufactured hypericin in an ointment combined with visible fluorescent light. Hypericin is one of the most photoactive compounds known - it is easily activated with relatively low-energy light. This makes it ideal for photodynamic therapy because it can be activated with fluorescent light instead of UV A or UV B light, which are associated with increased cancer risks. The mechanism by which the activated hypericin kills the T cells does not involve mutation of the DNA of the cells. Therefore, mutagenic risk is minimized.

HyBryte has demonstrated positive and statistically significant results in Phase I, II, and III clinical studies. Soligenix is currently working with the US FDA and EMA to design a second confirmatory Phase III study to support potential marketing approval.

In September 2021, the US FDA also granted Soligenix ODD for the treatment of T-cell lymphoma. In May 2021, Soligenix announced that HyBryte was awarded an "Innovation Passport" for the treatment of early-stage CTCL in adults under the United Kingdom's (UK's) Innovative Licensing and Access Pathway (ILAP).

KINSELBY (resminostat): 4SC AG

KINSELBY (resminostat) is an orally administered histone deacetylase (HDAC) inhibitor that potentially represents a novel therapy for a broad spectrum of oncology indications, both in monotherapy and particularly in combination with other anticancer drugs.

In preclinical models, resminostat has shown selectivity for class I, IIB, and IV HDAC enzymes with a particular specificity toward inhibiting the protein HDAC6, which is active in metastasis. Resminostat has the potential to provide significant benefits to patients by inhibiting tumor progression and metastasis, inducing tumor regression, and enhancing the body’s immune response to cancer.

In September 2023, the US FDA granted 4SC’s application for ODD for resminostat for CTCL.In October 2023, 4SC received ODD for resminostat in CTCL in the European Union. In March 2024, 4SC filed a Marketing Authorization Application (MAA) with EMA for resminostat.

CTCL Market Outlook

The overall management of CTCL across stages is complex; no unified standard of care or a universal algorithm exists. Consequently, different stages require different types of care, and following multidisciplinary management is essential. For example, all patients with advanced-stage disease also have skin lesions remaining from the early stage, and dermatologists should be involved in treating these lesions while administering other therapeutic agents simultaneously.

The treatment of CTCL (Mycosis fungoides and Sezary Syndrome) depends on the disease stage. Early-stage topical therapies include corticosteroids, retinoids, imiquimod, ultraviolet-An irradiation (PUVA), and total skin electron beam therapy. Systemic therapies are introduced in the advanced stages where the disease is widespread and/or resistant to topical treatment. Therapies include interferon-alpha injections, stem cell transplants, alemtuzumab (MabCampath), and other chemotherapy regimens.

The US FDA-approved drugs that are currently available include VALCHLOR (mechlorethamine), TARGRETIN (bexarotene), ADCETRIS (brentuximab vedotin), POTELIGEO (mogamulizumab) and others.

VALCHLOR (mechlorethamine) is the first and only FDA-approved formulation of mechlorethamine available for patients with stage IA and IB mycosis fungoides-type CTCL who have received prior skin-directed therapy.

The effective therapies that are used during the advanced stage (Stage IIB-IV) of CTCL are HDAC inhibitors, i.e., ISTODAX (romidepsin) and ZOLINZA (vorinostat). In 2006, vorinostat became the first drug approved for clinical use by the US Food and Drug Administration (FDA) for the treatment of progressive, persistent, or recurrent CTCL.

The CTCL pipeline possesses multiple potential drugs in late- and mid-stage developments to be launched shortly. Key players involved in robust research and development include SGX301 (Soligenix), I/ONTAK (E7777) (Citius Pharma), and Remetinostat (Medivir AB); these are some of the major players that are going to alter the market dynamics in the coming years.

CTCL Disease Understanding and Treatment

CTCL Overview

Lymphomas are cancers that originate in the lymphatic system, specifically from a type of white blood cell called a lymphocyte. The lymphatic system is an important part of the immune system and consists of the bone marrow, lymph nodes, thymus, liver, skin, and spleen. Lymphocytes are present in almost every organ. Therefore, lymphomas can begin to grow in any organ system, including the skin (which is considered the largest lymphoid organ in the human body). There are three different types of lymphocytes, each with a distinct function: B lymphocytes (B cells) that make antibodies to fight infections, T lymphocytes (T cells) that respond to specific threats posed by viruses and possibly cancers, and natural killer (NK) cells that are part of the innate immune response. It is important to determine the cell of origin, the B cell, T cell, or NK cell because that information determines the particular type of lymphoma and how to classify it.

Classification of lymphomas is forever evolving; however, they are broadly divided into two major categories: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Depending on the cell of origin, NHL can be subdivided into over 80 subtypes with differing growth patterns and biology. Treatment approaches for these subtypes vary, so it is important to know the patient’s NHL subtype. When NHL begins in the skin (not in another part of the lymphatic system such as the lymph nodes, organs, or lymph tissue) it is called a cutaneous (skin) lymphoma. A lymphoma that begins in the lymph nodes or another part of the body and then spreads to the skin is not considered a cutaneous lymphoma because it did not start in the skin. B-cell lymphomas have a higher incidence than T-cell lymphomas except in the skin
The most common type of CTCL is mycosis fungoides, Sezary syndrome and CD30 positive lymphoproliferative disorders (CD30+ LPDs).

Studies show that more than half the people who have CTCL develop itchy skin. Itchy skin tends to be more common if one have a more advanced stage of CTCL, or Sezary syndrome. The itch can be intense. As the cancer worsens, the itch can make it hard to sleep.Other symptoms of CTCL include fever, chills, weight loss, and feeling tired. Not everyone develops these symptoms.

CTCL Diagnosis

The diagnosis of CTCL is based upon a thorough clinical evaluation, detection of certain symptoms and physical findings, a detailed patient history, and various specialized tests. Such testing is necessary to confirm the specific type (and subtype) of CTCL, assess the nature and extent of the disease, and determine the most appropriate treatments.

As suggested by thorough patient history and clinical examination, various diagnostic tests may be recommended for those with suspected lymphoma. These may include biopsies, blood tests, specialized imaging tests, and/or additional tests.

Biopsies: Biopsies typically involve surgical removal and microscopic examination (i.e., histologic) of small samples of tissue cells gathered from CTCL skin lesions. A biopsy may confirm a diagnosis of CTCL. However, the skin lesions associated with the early stages of CTCL are challenging to distinguish from other skin conditions, such as psoriasis. Consequently, several biopsies performed over an extended period may be necessary to detect characteristic microscopic changes associated with CTCL. A separate test that is often used to help diagnose early-stage CTCL is T-cell receptor gene rearrangement analysis (TCRGR). This test can help identify specific re-arrangements of particular T-cell gene segments characteristic of most individuals with CTCL. The presence of identical twin T-cells may support the diagnosis of CTCL.

Blood tests: Blood tests may include studies to evaluate the number and appearance of white blood cells, red blood cells, and platelets; liver enzyme studies; tests to measure levels of the enzyme lactate dehydrogenase (LDH); and/or other studies. (High elevations of LDH may suggest that the lymphoma may have rapid progression, potentially requiring more intensive therapies). Blood tests may also be performed to detect the presence of characteristic cells (Sezary cells) in individuals with suspected Sezary syndrome.

CTCL Treatment

Several factors determine a patient’s treatment plan, including the person’s general health, age, and stage of the disease. Typically, treatment goals are to relieve symptoms, induce remission, and postpone disease progression. While patients with early-stage MF or SS may respond well to skin-directed therapies alone, patients with more advanced disease may require a combination of skin-directed (topical) and systemic (affecting the entire body) therapies to succeed.

Skin-Directed Therapies

Topical corticosteroids: Corticosteroids are part of the treatment regimen for some lymphomas and can temporarily reduce the associated symptoms of lymphoma, such as itching. These drugs are also good at reducing the swelling and inflammation associated with rapidly growing tumors. Topical corticosteroids may be prescribed in a cream, lotion, foam, gel, or ointment formulation.

Topical chemotherapy: Some chemotherapy drugs can be applied directly to skin lesions. Nitrogen mustard (mechlorethamine HCl, VALCHLOR gel) is approved by the US FDA for the topical treatment of Stage IA and IB MF-type CTCL in patients who have received previous skin treatment. Mechlorethamine HCL gel is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells. The most common side effects include redness, swelling, itching, skin ulcers or blisters, skin infection, and darkening of areas of the skin.

Topical retinoids: Retinoids are drugs related to vitamin A that can slow the growth of certain types of cancer cells. Bexarotene gel (TARGRETIN) and tazarotene (AVAGE, TAZORAC) are topical retinoids that can be applied directly to skin lesions. Bexarotene is the only topical retinoid approved by the FDA for the treatment of cutaneous lesions in patients with CTCL (Stages IA and IB) and who have refractory or persistent disease after other therapies or in patients who have not been able to tolerate other therapies.

Phototherapy (light therapy): Phototherapy, also known as “light therapy,” is a treatment that uses ultraviolet (UV) light, which is also found in sunlight. Ultraviolet light consists of ultraviolet A (UVA) rays and ultraviolet B (UVB) rays. Ultraviolet A and UVB radiation therapy is given using a special lamp or laser that directs the radiation beam to the target area on the skin. Phototherapy can be given to a specific area of the body or the entire body and can be used with other topical therapies.

Systemic Therapies

Oral retinoids: While some retinoids are applied directly to the skin, others are formulated as pills. Doctors use oral retinoids bexarotene (TARGRETIN), acitretin (SORIATANE), isotretinoin (ACCUTANE), and tretinoin (VESANOID) to treat MF and SS, but the FDA approves only bexarotene for treating MF. Common side effects include high numbers of fat particles in the bloodstream (hyperlipidemia) and low levels of thyroid hormones (hypothyroidism).

CTCL Epidemiology

The CTCL epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total incident population of CTCL, type-specific cases, gender-specific cases, stage-specific cases, and line-specific cases in the United States, EU4 countries (Germany, France, Italy, Spain) and the United Kingdom, and Japan from 2020 to 2034.

• In 7MM, the United States accounted for the highest number of incident cases of CTCL, which is 46.0% of the total incident population of CTCL in 7MM in 2023.
• In the US, out of all stage-specific cases of CTCL, Stage-IA accounted for highest number of cases, followed by Stage-IB and Stage-IIB cases in 2023.
• Among the EU4 and the UK, Germany accounted for the highest number of incident CTCL cases, followed by France, whereas Spain accounted for the lowest number of incident CTCL cases.
• In 2023, as far as gender-specific cases are concerned, males accounted for the higher number of CTCL cases in Japan. These cases are anticipated to increase by 2034.

KOL Views

To stay abreast of the latest trends in the market, we conduct primary research by seeking the opinions of Key Opinion Leaders (KOLs) and Subject Matter Experts (SMEs) who work in the relevant field. This helps us fill any gaps in data and validate our secondary research.

We have reached out to industry experts to gather insights on various aspects of CTCL, including the evolving treatment landscape, patients’ reliance on conventional therapies, their acceptance of therapy switching, drug uptake, and challenges related to accessibility. The experts we contacted included medical/scientific writers, professors, and researchers from prestigious universities in the US, Europe, the UK, and Japan.

Our team of analysts connected with more than 10 KOLs across the 7MM. By obtaining the opinions of these experts, we gained a better understanding of the current and emerging treatment patterns in the CTCL market, which will assist our clients in analyzing the overall epidemiology and market scenario.

Qualitative Analysis

We perform Qualitative and Market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst’s discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Conjoint analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, designation, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy. In efficacy, the trial’s primary and secondary outcome measures are evaluated. Based on these, the overall efficacy is evaluated.

Further, the therapies’ safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement

Because newly authorized drugs are often expensive, some patients escape receiving proper treatment or use off-label, less expensive prescriptions. Reimbursement plays a critical role in how innovative treatments can enter the market. The cost of the medicine, compared to the benefit it provides to patients who are being treated, sometimes determines whether or not it will be reimbursed. Regulatory status, target population size, the setting of treatment, unmet needs, the number of incremental benefit claims, and prices can all affect market access and reimbursement possibilities.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

CTCL Report Insights

• Patient Population
• Therapeutic Approaches
• CTCL Market Size and Trends
• Existing Market Opportunity

CTCL Report Key Strengths

• Eleven-year Forecast
• The 7MM Coverage
• CTCL Epidemiology Segmentation
• Key Cross Competition

CTCL Report Assessment

• Current Treatment Practices
• Reimbursements
• Market Attractiveness
• Qualitative Analysis (SWOT, Conjoint Analysis, Unmet needs)

Key Questions

• Would there be any changes observed in the current treatment approach?
• Will there be any improvements in CTCL management recommendations?
• Would research and development advances pave the way for future tests and therapies for CTCL?
• Would the diagnostic testing space experience a significant impact and lead to a positive shift in the treatment landscape of CTCL?
• What kind of uptake will the new therapies witness in the coming years in CTCL patients?