TNMB classification of CTCL
Lilly's file
This image is of a model and has been used for illustration only
Medical history
Name: Lilly West
Age: 29 years
Personal details: Non-smoker; low alcohol consumption (<1 unit per week)
Medical history: 5-year history of highly itchy, scaly skin patches (treated as eczema in primary care) which were unresponsive to treatment
Co-morbidities: Allergic rhinitis
Family history: Nothing of relevance
Previous treatments (prior to dermatology referral): Mild and potent topical corticosteroids
Current medication: Seasonal antihistamines
This case study is based on and adapted from a real patient; her name has been altered.
Consultant Dermatologist, Professor Julia Scarisbrick, talks through Lilly's case
Time to watch:
What do you think?
Is skin biopsy essential in the diagnosis of CTCL?
Find outBiopsy is essential to diagnose the clinicopathological subtype of CTCL. Multiple biopsies may be required to establish the diagnosis - especially in MF - with T-cell receptor gene analysis being a fundamental diagnostic and staging tool providing critical prognostic information.4-6
Real patient image,
used with permission
1
June 2009
Initial clinical presentation
- Lilly presented to the dermatology department with widespread hypopigmented and hyperpigmented patches and plaques affecting 15% body surface area (BSA)
- Skin biopsy confirmed CD4+ MF
- Staging investigations indicated stage IB: T2a N0 M0 B0
-
Baseline
mSWAT 20
Modified Severity‑Weighted Assessment Tool (mSWAT)10
- The mSWAT is a tool used to monitor skin tumour burden in active CTCL
- mSWAT can be calculated by using:
mSWAT = (patch BSA x1) + (plaque BSA x2) + (tumour BSA x4)
What do you think?
According to the British Association of Dermatologists (BAD) and the UK Cutaneous Lymphoma Group (UKCLG) guidelines, which skin‑directed therapies (SDTs) are suitable first-line treatment options for stage IB MF?
Find outSDTs are the first‑line treatment options for early‑stage MF. These include topical therapies such as chlormethine gel and topical corticosteroids. Topical bexarotene gel, however, is not licensed in the UK. Other first‑line SDT options include phototherapy and localised radiotherapy.4
Real patient image, used with permission
2
December 2009-October 2011
Early management
Modified Severity‑Weighted Assessment Tool (mSWAT)10
- The mSWAT is a tool used to monitor skin tumour burden in active CTCL
- mSWAT can be calculated by using:
mSWAT = (patch BSA x1) + (plaque BSA x2) + (tumour BSA x4)
IFNα2: human interferon alpha-2; mSWAT: modified Severity-Weighted Assessment Tool; MU: million units; PUVA: psoralens ultraviolet A; s/c: subcutaneously; UVB: ultraviolet B
Rather than switch to an alternative treatment regimen when she developed side effects with interferon, Lilly chose to stop all treatments because she wanted to conceive a child.
3
October 2011-July 2013
'Watch and wait'
Expectant therapy
('watch and wait')
- Slow progression of patches/ plaques over the following year
mSWAT 30 (10% patch, 10% plaque)
Pregnancy in December 2012
- Further progression of plaques
mSWAT 40 (20% plaque)
Real patient image,
used with permission
Onset of small domed tumours
- 15 weeks pregnant: painful small tumour on back excised (limited treatment options available at this stage)
Real patient image,
used with permission
Continued development of small tumours into final trimester
- Histology showed tumour‑stage MF, CD30+ 10%, no large‑cell transformation
- Discussion with obstetrician for elective c-section at 34 weeks
- July 2013: birth of baby boy
Guidance in women of childbearing potential, pregnancy and lactation1
Women of childbearing potential: Women of childbearing potential should be using two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment.
Pregnancy: ADCETRIS should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the foetus. If a pregnant woman needs to be treated she should be clearly advised on the potential risk to the foetus. There are no data from the use of ADCETRIS in pregnant women. Studies in animals have shown reproductive toxicity.
Breast-feeding: A decision should be made whether to discontinue breast-feeding or to discontinue/ abstain from this therapy, taking into account a potential risk of breast-feeding for the child and the benefit of therapy for the woman. There are no data as to whether ADCETRIS or its metabolites are excreted in human milk. A risk to the newborn/ infant cannot be excluded.
Refer to the ADCETRIS Summary of Product Characteristics for further information.
4
August 2013-September 2014
Postpartum clinical course
- Staging investigations revealed stage IIB: T3 N0 M0 B0
- Radiotherapy to tumours (8 Gy in two fractions)
- mSWAT score 50 (5.75% patch, 22.3% plaque)
- Lilly is not pregnant, is not breast-feeding, has CD30+ MF, and has previously received one prior line of systemic therapy
- She was enrolled onto the ALCANZA clinical trial 8 weeks after giving birth - receiving 1.8 mg/kg ADCETRIS once every 3 weeks for 16 cycles
ADCETRIS is indicated for the treatment of adult patients with CD30+ cutaneous T-cell lymphoma (CTCL) after at least 1 prior systemic therapy.1
Guidance in women of childbearing potential, pregnancy
and lactation1
BAD/ UKCLG MF treatment guidelines for stage IIB
The ALCANZA clinical trial11
Phase III, randomised, open‑label trial
Adults with CD30+ MF or primary cutaneous anaplastic large cell lymphoma that had received at least one previous systemic therapy
ADCETRIS 1.8 mg/kg in 3-weekly cycles for up to 16 cycles vs physician's choice,* for up to 48 weeks
Primary endpoint: objective global response lasting ≥4 months (ORR4) by independent review facility
Key secondary endpoints: CR, PFS, symptom burden (as measured by symptom domain of Skindex‑29 questionnaire)
ALCANZA clinical trial results11
Median follow-up time: 22.9 months
ADCETRIS
ORR4
56.3%
(n=36/64)
VS
Physician's choice*
ORR4
12.5%
(n=8/64)
Between group difference of 43.8%
(95% CI: 29.1-58.4); p<0.0001
Median PFS was longer in patients receiving ADCETRIS versus physician's choice of treatment (key secondary endpoint):
ADCETRIS
mPFS
16.7
months
VS
Physician's choice*
mPFS
3.5
months
HR: 0.27 (95% CI: 0.17-0.43);
p<0.0001
*Physician's choice: bexarotene 300 mg/m² once per day or methotrexate 5‑50
mg once per week.
CR: complete response; FDA: US Food and Drug Administration;
PFS: progression‑free survival
Lilly's response in the ALCANZA trial
Baseline
(August 2013)
Close‑up of a selected plaque and tumour on Lilly’s skin
Plaque
Tumour
Real patient images, used with permission
Cycle 9
(March 2014)
End of treatment
(September 2014)
Close‑up of a selected plaque and tumour on Lilly’s skin
Plaque
Tumour
Real patient images, used with permission
mSWAT
HRQoL
(Skindex-29 score; 0-100 scale)
Objective global response
Baseline
Cycle 6
Cycle 12
End of treatment (Cycle 16)
N/A
PR
PR
PR
50
15
3
3
50
100
100
80
- No significant adverse events
- No recurrence of tumours
- Good partial response in skin
ALCANZA tolerability data11
In the ALCANZA study, serious adverse events (AEs) occurred in 29% (n=19/66) of patients receiving ADCETRIS and 29% (n=18/62) of patients receiving physician's choice. 16 patients receiving ADCETRIS discontinued the study, versus five patients receiving physician's choice.
The most common, any-grade AEs reported by patients receiving ADCETRIS or physician's choice (methotrexate/bexarotene) included peripheral sensory neuropathy (45% vs 4%/0%), nausea (36% vs 16%/11%), diarrhoea (29% vs 4%/8%), fatigue (29% vs 20%/32%), vomiting (17% vs 8%/3%), alopecia (15% vs 4%/3%), pruritus (17% vs 8%/16%) and pyrexia (17% vs 28%/11%).
Note, when considering treatment with ADCETRIS, extra precautions should be taken with respect to women of childbearing potential, pregnancy, breastfeeding and fertility.1
Guidance in women of childbearing potential, pregnancy and lactation1
Women of childbearing potential: Women of childbearing potential should be using two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment.
Pregnancy: ADCETRIS should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the foetus. If a pregnant woman needs to be treated she should be clearly advised on the potential risk to the foetus. There are no data from the use of ADCETRIS in pregnant women. Studies in animals have shown reproductive toxicity.
Breast-feeding: A decision should be made whether to discontinue breast-feeding or to discontinue/ abstain from this therapy, taking into account a potential risk of breast-feeding for the child and the benefit of therapy for the woman. There are no data as to whether ADCETRIS or its metabolites are excreted in human milk. A risk to the newborn/ infant cannot be excluded.
Refer to the ADCETRIS Summary of Product Characteristics for further information.
5
September 2014-September 2016
Subsequent clinical course
Donor leukocyte infusions are a form of immunotherapy that can enhance the graft‑versus‑tumour effect in situations of mixed chimerism, molecular disease relapse or as prophylaxis in high-risk haematologic malignancies, following HLA-matched allogeneic haematopoietic cell transplantation.12
ATG: antithymocyte globulin; CR: complete response; HLA: human leukocyte antigen; TLI: total lymphoid irradiation; TSEBT: total skin electron beam therapy
Real patient image, used with permission
6
In conclusion
- Lilly returned to work at the end of 2016
- She has post-inflammatory hyperpigmentation (shown in image)
- At the time of case study development, Lilly remained in CR with no graft‑versus‑host disease
Case 2: a young woman with pcALCL.
Follow the case Case 3: an elderly gentlemen with a three‑decade history of CTCL. Follow the case
pcALCL: primary cutaneous anaplastic large cell lymphoma
