Treating eligible adult patients with relapsed/ refractory CTCL

with ADCETRIS^® (brentuximab vedotin)¹

Explore three interactive case studies based on and adapted from real‑life patients, alongside expert video commentary

Cutaneous T‑cell lymphoma (CTCL) is a rare and heterogeneous group of non‑Hodgkin lymphomas primarily manifesting in the skin, but which may also involve lymph nodes, blood and visceral organs. Classic subtypes of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS), each presenting with distinct clinical and histopathological features.^2,3 MF accounts for 60% of all CTCLs.²

ADCETRIS is indicated for the treatment of adult patients with CD30+ CTCL after at least one prior systemic therapy.¹

These case studies have been provided by:

Professor Julia Scarisbrick

Consultant Dermatologist at the Centre for Rare Diseases, University Hospital Birmingham and President of the International Society of Cutaneous Lymphomas

Dr Dima El-Sharkawi

Consultant Haematologist at The Royal Marsden

Dr Stella Williams

Consultant in Haemato-Oncology at The Clatterbridge Cancer Centre

These cases reflect the experiences of individual patients using ADCETRIS in their treatment journeys and may not represent all patient experiences; individual outcomes and responses to treatments can vary.

In the following case, Amira has been diagnosed with CD30-positive primary cutaneous anaplastic large‑cell lymphoma (pcALCL). EORTC and WHO categorise pcALCL as a subtype of CTCL.⁴ It is the most common subtype after MF, presenting as isolated or clustered cutaneous papules or nodules ‑ commonly ulcerated and with rapid growth ‑ without systemic involvement at the time of diagnosis and initial staging.⁵ ISCL and EORTC have defined a separate staging system for non‑MF/ non‑SS CTCL.⁴

Amira's file

This image is of a model and has been used for illustration only

Medical history

Name: Amira Jalal

Age: 18 years

Personal details: Student; non-smoker; nil alcohol

Medical history: ALK-negative (ALK-) pcALCL (first diagnosed in June 2020)

Co-morbidities: Hypothyroidism, xeroderma pigmentosum (XP)

Family history: No lymphomas, other cancers or autoimmune diseases

Previous treatments (prior to haematology referral): Antibiotics (topical and oral)

Current medication: Levothyroxine

This case study is based on and adapted from a real patient; her name has been altered.

Consultant Haematologist, Dr Dima El-Sharkawi, talks through Amira's case

Time to watch:

Stock image, for illustrative purposes only

May - June 2020

Initial clinical presentation

Amira presented to the dermatology department with multiple ulcers to her left shin
Lesions were treated in primary care with antibiotics (ineffective)
Biopsy of the lesions revealed diffuse dermal infiltrate of large anaplastic lymphoid cells; ALK-; >75% CD30 positivity
Diagnosis: ALK- pcALCL
XP precludes the use of radiotherapy
Referred to haematology

What do you think?

How could the presence of XP influence the management of pcALCL?

Find out

XP is a genetic disorder characterised by sensitivity to sun/UV exposure due to a defect in the nucleotide excision repair pathway. The result is an increased sensitivity to UV radiation and a predisposition towards developing skin cancers.⁶ Although XP has been linked to other malignancies, no connection has been established between XP and lymphoma.^6,7

In terms of management of pcALCL, radiation therapy should be avoided due to the presence of XP.⁷

August 2020-August 2021

First-line treatment

BAD and UKCLG recommend surgical excision and/or radiotherapy for localised disease.⁴ In Amira's case, due to the multiplicity of ulcers and concerns around using radiotherapy due to XP, chemotherapy with methotrexate was administered as first‑line treatment.

After achieving a partial response with methotrexate, new ulcers on Amira’s left shin in August 2021 marked disease progression.

September 2021-February 2022

Second-line treatment

After 6 months on weekly vinblastine chemotherapy, Amira achieved a partial response to the ulcers on her left shin but developed new lesions near her left eye.

Re-biopsy: Diagnosis of pcALCL reconfirmed with biopsy of new lesions.

March 2022-May 2023

Third-line treatment

NICE TA577⁸

Brentuximab vedotin is recommended as an option for treating CD30 positive cutaneous T cell lymphoma after at least 1 systemic therapy in adults, only if:

they have mycosis fungoides stage IIB or over, primary cutaneous anaplastic large cell lymphoma or Sézary syndrome and
the company provides brentuximab vedotin according to the commercial arrangement

Common adverse events associated with ADCETRIS as monotherapy:

The most frequent adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhoea, pyrexia, neutropenia, upper respiratory tract infection, arthralgia, rash, cough, vomiting, pruritus, peripheral motor neuropathy, infusion‑related reactions, constipation, dyspnoea, myalgia, weight decrease and abdominal pain.¹

Treatment break: Amira's sixth treatment cycle was delayed after she developed a chest infection. After her infection had resolved, Amira restarted ADCETRIS at the same dose and frequency and completed 16 cycles of treatment.

In conclusion

At the time of case study development, Amira remains in remission, with no active ulcers
She was under routine follow-up with the haematology department

Non-MF/ non-SS PC lymphomas

BAD/ UKCLG
guidelines

Reimbursement

Patient notes

References

ADCETRIS summary of product characteristics. Available at: https://www.medicines.org.uk/emc/product/2859/smpc.
Willemze R, Cerroni L et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood 2019;133:1703-1714
Willemze R, Hodak E et al. Primary cutaneous lymphomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29:iv30-iv40
Gilson D, Whittaker S J et al. British association of dermatologists and UK Cutaneous Lymphoma Group guidelines for the management of primary cutaneous lymphomas 2018. Br J Dermatol 2019;180:496-526
Ortiz-Hidalgo C, Pina-Oviedo S. Primary cutaneous anaplastic large cell lymphoma-a review of clinical, morphological, immunohistochemical, and molecular features. Cancers (Basel) 2023;15:4098
DiGiovanna J J, Kraemer K H. Shining a light on xeroderma pigmentosum. J Invest Dermatol 2012;132:785-796
Lucero R, Horowitz D. Xeroderma pigmentosum. Statpearls. Treasure Island (FL) ineligible companies. Disclosure: David Horowitz declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC., 2024
National Institute for Health and Care Excellence (NICE). Technology appraisal 577. Brentuximab vedotin for treating CD30-positive cutaneous T-cell lymphoma, 24 April 2019. Available at: https://www.nice.org.uk/guidance/ta577/resources/brentuximab-vedotin-for-treating-cd30positive-cutaneous-tcell-lymphoma-pdf-82607147844037.
All Wales Therapeutics and Toxicology Centre (AWTTC). Medicine recommendation: brentuximab vedotin (ADCETRIS^®). January 2018. Available at: https://awttc.nhs.wales/accessing-medicines/medicine-recommendations/brentuximab-vedotin-adcetris2/.
Scottish Medicines Consortium. SMC2229, 6 December 2019. Available at: https://scottishmedicines.org.uk/medicines-advice/brentuximab-adcetris-full-smc2229/.
Department of Health, Northern Ireland. NICE-endorsed technology appraisals 2019-2020. Available at: https://www.health-ni.gov.uk/articles/nice-endorsed-technology-appraisals-20192020.

NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/ publication.

Stage	First-line options		Second-line options		Third-line options
IA-IIA	SDT		Bexarotene* Interferon TSEBT	PD^†	Clinical trials Stage IIB options
IIB	SDT TSEBT Bexarotene* Interferon		Brentuximab vedotin Clinical trials	PD^†	Chemotherapy RIC-allo-SCT Clinical trials

Adapted from Gilson D et al, 2019⁴
*Bexarotene gel is not licensed in the UK.⁴
†PD and patches, plaques and tumours.⁴

BAD: British Association of Dermatologists; MF: mycosis fungoides; PD: progressive disease; RIC̽allo̽SCT: reduced‑intensity allogeneic stem cell transplantation; SDT: skin‑directed therapy; TSEB: total skin electron beam therapy; UKCLG: UK Cutaneous Lymphoma Group

Reference: 4. Gilson D, Whittaker S J et al. Br J Dermatol 2019;180:496-526

Stage	First-line options		Second-line options		Third-line options
IIB	SDT TSEBT Bexarotene* Interferon		Brentuximab vedotin Clinical trials	PD^†	Chemotherapy RIC-allo-SCT Clinical trials

Adapted from Gilson D et al, 2019⁴
*Bexarotene gel is not licensed in the UK.⁴
†PD and patches, plaques and tumours.⁴

BAD: British Association of Dermatologists; MF: mycosis fungoides; PD: progressive disease; RIC‑allo‑SCT: reduced‑intensity allogeneic stem cell transplantation; SDT: skin‑directed therapy; TSEB: total skin electron beam therapy; UKCLG: UK Cutaneous Lymphoma Group

Reference: 4. Gilson D, Whittaker S J et al. Br J Dermatol 2019;180:496-526

Localised disease	Extensive cutaneous disease or systemic progression
Radiotherapy	Chemotherapy
Radiotherapy	ADCETRIS^® (brentuximab vedotin)

Adapted from Gilson et al, 2019⁴

ADCETRIS is indicated for the treatment of adult patients with CD30+ cutaneous T‑cell lymphoma after at least one prior systemic therapy.¹

BAD: British Association of Dermatologists; pcALCL: CD30-positive primary cutaneous anaplastic large-cell lymphoma; UKCLG: UK Cutaneous Lymphoma Group

References: 1. ADCETRIS SPC. 4. Gilson D et al. Br J Dermatol 2019;180:496-526

T1	Solitary skin involvement: T1a: <5 cm diameter T1b: >5 cm diameter
T2	Regional skin involvement with multiple lesions limited to one body region or two contiguous body regions; all disease encompassing a circular area with: T2a <15 cm diameter T2b >15 cm to <30 cm diameter T2c >30 cm diameter
T3	Generalised skin involvement with multiple lesions involving: T3a - two non-contiguous body regions T3b - at least three body regions

N0	No clinical or pathological lymph node involvement
N1	Involvement of one peripheral lymph node region that drains an area of current or prior skin involvement
N2	Involvement of two or more peripheral lymph node regions or involvement of any lymph node region that does not drain an area of current or prior skin involvement
N3	Involvement of central lymph nodes

M0	No evidence of extracutaneous non-lymph node disease
M1	Extracutaneous non-lymph node disease present

Amira's file

Medical history

Consultant Haematologist, Dr Dima El-Sharkawi, talks through Amira's case

May - June 2020

Initial clinical presentation

What do you think?

August 2020-August 2021

First-line treatment

September 2021-February 2022

Second-line treatment

March 2022-May 2023

Third-line treatment

NICE TA5778

In conclusion

References

NICE TA577⁸