TNMB classification of CTCL
Elias's file
This image is of a model and has been used for illustration only
Medical history
Name: Elias Beck
Age: 70 years
Personal details: Non-smoker; nil alcohol
Medical history: CTCL (first diagnosed in 1992)
Co-morbidities: Vitamin D deficiency, chondrodermatitis
Family history: Nothing of relevance
Previous treatments (prior to haematology referral):
- Jan 2017: R buttock, R thigh, R shin, R foot
- Oct 2017: finger
- Dec 2017: face
- Jan 2018: sternum, hands, L forearm, forehead
1992: PUVA
2015: TSEBT (12 Gy in 8# over 2 weeks)
2016: TSEBT (30 Gy in 20# over 4 weeks)
2017-18: Radiotherapy (8 Gy in 2#) to patch disease:
2019: Oral bexarotene and subcutaneous interferon
Medication history: Potent topical steroids, antibiotic/ steroid combination topical preparation, emollient, oral bexarotene and subcutaneous interferon
This case study is based on and adapted from a real patient; his name has
been altered.
#: number of fractions; Gy: Gray (standard unit of ionising radiation);
L: left; PUVA: psoralen and ultraviolet A; R: right;
TSEBT: total skin electron beam therapy
Consultant Haemato-Oncologist, Dr Stella Williams, talks through Elias's case
Time to watch:
1
2020
Initial clinical presentation
-
Elias presented to the haematology department with stage CD30+ MF
- 10%‑15% CD30 positivity (from biopsy in 2019)
- Currently managed with bexarotene and interferon
- Skin generally responding to treatment
- Normal renal function
- Mild thrombocytopenia and neutropenia
- Tiny population of Sézary cells in peripheral blood
- Bexarotene and interferon treatment continued with G-CSF support
G-CSF: granulocyte colony-stimulating factor
What do you think?
When is G‑CSF recommended as an adjunct to chemotherapy?
Find outGuidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend prophylactic G-CSF use when using a chemotherapy regimen where the associated risk of febrile neutropenia (FN) is ≥20%. Risk is dependent on the chemotherapy as well as individual patient risk factors such as age, performance status and disease stage.8,9 The increased risk of FN for patients aged 65 and older should get special attention.8
In Elias's case, G‑CSF was started after the development of neutropenia. There is a risk of leukopenia with bexarotene and neutropenia/ thrombocytopenia with interferon.10,11
2
2020-2021
Initial treatment under haematology
Elias's treatment continued for another year with no additional radiotherapy needed during this time. Treatment‑related side effects were managed accordingly.
CTCL treatment
Side effect
Treatment/ modification
Bexarotene (po)
and interferon (s/c)
Good skin response
Hyperlipidaemia
Hypothyroidism
Neutropenia
Statin followed by fibrate therapy
Levothyroxine initiated
Intermittent G‑CSF
3
2021
Disease progression
March 2021: Elias's CTCL progressed
Biopsy showed diffuse CD30 positivity
- Dermal: 30% CD30+ cells (majority of large cells are CD30 positive)
- Epidermotropic: 70%-80% CD30+ cells
Elias's CTCL re‑staged to IIB MF
4
2021-2022
Treatment with ADCETRIS
ADCETRIS is indicated for the treatment of adult patients with CD30+ CTCL after at least one prior systemic therapy.1
With stage CD30+ MF, Elias is eligible for treatment with ADCETRIS, in line with NICE TA577, SMC2229 and BAD/ UKCLG treatment guidelines.4,12-15
Elias starts treatment with ADCETRIS in May 2021
- Dose: 1.8 mg/kg IV over 30 mins
- Frequency: every 3 weeks
- Treatment course: 16 cycles
PN: peripheral neuropathy
Elias's skin lesions showed a good response to treatment with ADCETRIS, with almost complete resolution of skin lesions by cycle 13 except one resistant plaque on the left thigh. He received radiotherapy to the resistant plaque (8 Gy in 2#) in November 2022 and booster radiotherapy in July 2023 (12 Gy in 3#).
Elias's treatment-related adverse events with ADCETRIS
He experienced grade 1 PN after the second cycle on ADCETRIS; however, he maintained treatment dose and frequency until PN advanced to grade 2 following cycle 7; cycle 8 was deferred until PN returned to ≤grade 1 and subsequent cycles were given at a reduced dose (1.2 mg/kg); PN worsened after cycle 10, so cycle 11 was deferred until PN returned to ≤grade 1. Remaining cycles were administered at the same dose and interval (1.2 mg/kg every 3 weeks). He completed 16 cycles in May 2022.
For further information on management of PN please refer to the ADCETRIS Summary of Product Characteristics.
What do you think?
Would you consider switching treatment after Elias began experiencing PN with ADCETRIS?
Find outPeripheral sensory neuropathy and peripheral motor neuropathy are very common (≥1/10) side effects in patients receiving ADCETRIS. If PN emerges or worsens during treatment with ADCETRIS monotherapy, effects can be managed via dosing and schedule modifications as follows:1
| PN severity* | Drug modification |
|---|---|
| Grade 1 | Continue with same dose and schedule |
| Grade 2 or 3 | Withhold dose until toxicity returns to ≤grade 1 or baseline, then restart treatment at a reduced dose: 1.2 mg/kg up to a maximum of 120 mg every 3 weeks |
| Grade 4 | Discontinue treatment |
For further information please refer to the ADCETRIS Summary of Product Characteristics.
*Grading used to define PN severity:16
PN grading severity is based on National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events v4.03.
| Grade 1 | Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated |
| Grade 2 | Moderate; minimal, local or non-invasive intervention indicated; limiting instrumental activities of daily living |
| Grade 3 | Severe or medically significant but not immediately life-threatening; hospitalisation or prolongation of hospitalisation indicated; disabling; limiting activities of daily living integral to self‑care |
| Grade 4 | Life-threatening consequences; urgent intervention indicated |
If neutropenia develops with ADCETRIS as monotherapy, treatment should be managed by dose delays as follows: 1
- Grade 1 or grade 2 continue with same dose/ schedule
- Grade 3 or grade 4 withold dose until toxicity returns to ≤grade 2 or baseline then resume treatment at the same dose and schedule*.
*Patients who develop grade 3 or grade 4 lymphopenia may continue treatment without interruption. Consider G‑CSF or GM‑CSF in subsequent cycles for patients who develop Grade 3 or Grade 4 neutropenia.
GM-CSF: Granulocyte-Macrophage Colony-Stimulating Factor
5
In conclusion
- At the time of case study development, Elias had been discharged to dermatology with an almost complete response to his skin lesions
- He was being actively monitored. Dermatology was considering administering chlormethine gel to the resistant plaque on his left thigh
