The clinical and humanistic burden of cutaneous T-cell lymphomas and response to conventional and novel therapies: results of a systematic review

Figures & data

Figure 1. Systematic review study flows. Left, clinical burden review. Right, clinical efficacy review.

Table 1. Studies assessing the impact of cutaneous T-cell lymphomas on HRQoL in patients with relapsed and/or refractory disease.

Author, study design, population	QoL domains assessed	HRQoL instrument	Findings
Benyon et al., 2015 [17] Qualitative study CTCL patients (n = 19) UK	Symptoms, physical, functional, mental, emotional, and social impact	Qualitative in-depth semi-structured interviews with CTCL patients	Themes identified as being of concern to patients with CTCL Physical well-being: CTCL had a negative impact on patients’ physical well-being with skin problems, painful hands and feet, temperature regulation problems, pruritus, and sleep problems reported Practical concerns: CTCL negatively affected the everyday activities of patients including travel, leisure, and attending clinical appointments Psychological and social well-being: CTCL patients reported that the disease negatively affected their self-image and relationships. Uncertainty of response to treatments and symptom development was an additional difficulty reported to make long-term planning difficult for patients
Bouwhuis et al., 2003 [18] Physical and mental health survey Patients with Sezary syndrome (n = 20) USA	Symptoms, physical, functional, mental, emotional, and social impact	SF-36	SF-36 scale score^a, mean (SD) Bodily pain, 44.0 (12.3) General health, 37.8 (10.4) Physical function, 40.7 (13.0) Role – physical function, 41.4 (12.0) Vitality, 42.1 (12.7) Mental health, 45.2 (10.9) Role – emotional functioning, 48.4 (13.3) Social functioning, 40.0 (10.5) Mental component, 46.2 (12.1)
Demierre et al., 2005 [41] Monocenter, cross-sectional study CTCL patients (n = 22) USA	Symptoms, physical, functional, mental, emotional, and social impact	FACT-G	Domain, mean (SD) Physical All patients, 22.7 (5.7) Early-stage disease, 25.4 (2.5) Late-stage disease, 20.5 (6.7) Functional All patients, 19.0 (6.6) Early-stage disease, 22.9 (4.2) Late-stage disease, 15.8 (6.6) Emotions All patients, 17.9 (5.9) Early-stage disease, 21.6 (3.3) Late-stage disease, 14.9 (6.0) Social/Family (SD) All patients, 22.3 (4.9) Early-stage disease, 24.1 (3.8) Late-stage disease, 20.7 (5.3)
		Skindex 29	Domain, mean (SD) Physical All patients, 19.1 (7.2) Early-stage disease, 15.2 (6.6) Late-stage disease, 22.4 (6.2) Functional All patients, 24.2 (10.4) Early-stage disease, 18.1 (7.5) Late-stage disease, 29.3 (10.0) Emotions All patients, 23.9 (8.9) Early-stage disease, 18.1 (7.2) Late-stage disease, 28.7 (7.3)
Demierre et al., 2006 [19] 2005 National Cutaneous Lymphoma Foundation Survey The United States membership of the Mycosis Fungoides Foundation (n = 630) USA	Symptoms, physical, functional, mental, emotional, and social impact	Self-administered questionnaire	Proportion (%) of patients for whom daily activities were negatively affected by CTCL Interferes with job, 45.2 Limits family activities, 42.3 Interferes with keeping a job, 26.3 Missed work or school, 54.9 Limits daily activities, 50.2 Forced to stay in bed, 25.4 Makes you tired, 65.7 Tend to stay at home, 38.2 Affects your social life, 47.8 Affects your desire to be with people, 40.8 Affects how well you sleep, 59.9 Feel financially burdened, 60.5 Content with your current QoL, 83.3 Proportion (%) of patients for whom psychosocial activities were negatively affected by CTCL Worried about dying, 80.2 Worried disease may be serious, 93.8 Makes you feel depressed. 72.7 Feel frustrated about disease, 86.6 Feel ashamed about disease, 39.0 Feel angry about disease, 63.5 Satisfied with coping, 71.5 Interferes with sex, 47.3 Feel unattractive, 63
Demierre et al., 2007 [43] Prospective pilot study CTCL patients (n = 11) USA	Symptoms, physical, functional, mental, emotional, and social impact	FACT-G	FACT-G score at baseline, mean (SD): Physical, 23.9 (2.7) Functional, 18.6 (5.6) Emotional, 18.3 (5.1) Social, 20.3 (4.9) Total, 81.1 (18.3) FACT-G score at follow-up, mean (SD) Physical, 23.9 (3.3) Functional, 19.9 (7.3) Emotional, 19.4 (3.5) Social, 20.2 (5.8) Total, 83.4 (19.9)
		Skindex-29	Skindex-29 score at baseline, mean (SD) Functional, 26.2 (8.6) Symptoms, 21.4 (4.3) Emotional, 27.2 (9.7) Total, 74.9 (22.7) Skindex-29 score at follow-up, mean (SD) Functional, 22.0 (8.8) Symptoms, 15.6 (7.0) Emotional, 22.2 (6.5) Total, 59.8 (22.2)
Porkert et al., 2016 [22] Cross-sectional study CTCL or CBCL patients (n = 92) Austria	Mental, emotional, and social impact	Skindex-29, IPQ-R, Scale for assessment of illness behavior tool, VASitch	Advanced-stage MF/SS (n = 19) was associated with higher HRQoL impairment than early-stage disease (n = 36). Patients with advanced-stage disease had a high emotional burden with poor belief in treatment or personal control. Patients with non-MF/SS or CBCL were relatively unaffected by disease with no reduction in HRQoL, and high perception of treatment and personal control.
Prince et al., 2017 [40,53]	Symptoms, emotional and functional impact	Skindex-29, FACT-G, and EQ-5D	Skindex-29, mean maximum reduction (SD) Symptoms domain● Brentuximab vedotin, –27.96 (26.877), p < 0.0001● PC, –8.62 (17.013)● Brentuximab vedotin-treated patients with: ● Peripheral neuropathy, –35.54● No neuropathy, –11.11 Symptoms burden● Brentuximab vedotin-treated patients with: ● Peripheral neuropathy, –36.72● No neuropathy, –33.33 Median time to improvement (MID = 12.3)^b● Brentuximab vedotin, 2.1 months● PC, 5.0 months Median time to improvement (MID = 9.0)^c: ● Brentuximab vedotin, 2.1 months● PC, 3.9 months Median duration of improvement (MID = 12.3)^b● Brentuximab vedotin, 10.6 months● PC, 3.5 months Median duration of improvement (MID = 9.0)^c● Brentuximab vedotin, not estimable● PC, 4.2 months FACT-G Mean change from baseline● Brentuximab vedotin, 0.15● PC, −2.29 EQ-5D Mean change from baseline US time trade-off● Brentuximab vedotin, 0.02● PC, –0.02 UK time trade-off● Brentuximab vedotin, 0.03● PC, –0.04 Visual analogue scores● Brentuximab vedotin, 0.80 PC, –2.00
Sampogna et al., 2009 [42] Physical and mental health survey CTCL or CBCL patients (n = 95) Italy	Symptoms, physical, functional, mental, emotional, and social impact	Skindex-29	Domain score, mean (SD) Functional, 17.4 (22.5) Emotions, 27.3 (23.7) Symptoms, 21.3 (24.2)
		EORTC QLQ-C30	EORTC QLQ-C30 score, mean (SD) Global health status, 73.6 (23.7) Physical function, 90.4 (15.8) Role function, 92.0 (16.6) Emotional function, 71.0 (28.0) Cognitive function, 84.1 (18.4) Social function, 86.2 (23.9) Fatigue, 21.3 (26.1) Nausea, 4.3 (20.9) Pain, 5.8 (12.9) Dyspnea, 10.1 (23.4) Insomnia, 23.2 (30.9) Financial problems, 7.2 (22.4)
Talpur et al., 2015, 2016 [21,39] Phase II study Patients with MF or LyP treated with brentuximab vedotin (n = 62, 23 LyP, 39 MF) USA	Symptoms, physical, functional, mental, emotional, and social impact	Skindex-29	Change in Skindex-29 score from baseline to end of study, median (min, max) MF Emotion, –10 (–65, 35) Symptoms, –7.14 (–46.43, 42.86) Function, – 2.08 (–50.38, 27.08) LyP Emotion, –22.50 (–61.94, 12.50) Symptoms, –10.71 (–53.57, 28.57) Function, –16.29 (–44.70, 14.58)
		MDASI score	Baseline MDASI-AUC, mean (min, max) MF Pain, 0.349 (0.196, 1.322) Fatigue, 0.596 (0.461, 2.305) Sleep, 0.551 (0.436, 2.237) Distress, 0.473 (0.269, 1.711) Enjoyment of life, 0.468 (0.250, 1.974) LyP Pain, 0.216 (0.000, 0.720) Fatigue, 0.437 (0.375, 1.140) Sleep, 0.221 (0.126, 0.780) Distress, 0.253 (0.269, 0.625) Enjoyment of life, 0.170 (0.222, 0.375) Change in MDASI scales from baseline to end of study, mean (SD, range) MF Severity, 0.18 (1.96, –5.85–3.15) Interference, 0.06 (3.07, –9.17–5.17) LyP Severity, 0.46 (1.61, –1.69–5.0) Interference, 0.11 (1.59, –3.0–4.67)
		VASitch	VASitch score, mean (median) MF At baseline, 5.54 (6.00) At end of study, 5.26 (5.00) LyP At baseline, 2.95 (0.00) At end of study, 2.76 (3.00)
Vij et al., 2012 [37] Retrospective analysis CTCL patients (n = 486) USA	Symptoms, physical and functional impact	VASitch	Mean pruritus value (SEM) All patients, 4.2 (0.18) Early-stage disease, 3.4 (0.19) Late-stage disease, 6.6 (0.36) Mycosis fungoides, 3.6 (0.18) Sezary syndrome, 7.7 (0.37)
Wright et al., 2013 [38] Cross-sectional observational study CTCL patients, all disease stages (n = 100) UK	Symptoms, physical and functional impact	VASitch	VASitch score, mean (SD, range) 3.35 (3.1, 0–10)
		Skindex-29	Skindex-29 score, mean (SD, range) Total Skindex-29, 43.3 (27.7, 0–100) Emotional subscale, 15.8 (10.3, 0–40) Symptom subscale, 11.3 (6.5, 0–23) Function subscale, 16.1 (13.4, 0–41)

CBCL, cutaneous B-cell lymphoma; CTCL, cutaneous T-cell lymphoma; EORTC QLQ, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; FACT-G, Functional Assessment of Cancer – General; LyP, lymphomatoid papulosis; MDASI, MD Anderson Symptom Inventory; MF, mycosis fungoides; MID, minimal important difference; PC, physician’s choice; QoL, quality of life; SD, standard deviation; SEM, standard error of the mean; SF-36, SR, systematic review; VAS, visual analogue scale.

^aEach scale is normalized to a mean of 50 so that a score of 50 is considered normal.

^bAssuming a MID of 12.3, which was reached by 40/64 patients receiving brentuximab vedotin and 25/64 receiving physician’s choice.

^cAssuming a MID of 9.0, which was reached by 40/64 patients receiving brentuximab vedotin and 25/64 receiving physician’s choice.

Figure 2. Overall response rates reported in patients treated for refractory cutaneous T-cell lymphomas.

Figure 3. Complete response rates reported in patients treated for refractory cutaneous T-cell lymphomas.

Figure 4. PFS reported in patients treated for refractory cutaneous T-cell lymphomas.

Figure 5. DOR reported in patients treated for refractory cutaneous T-cell lymphomas.

Beynon T, Selman L, Radcliffe E, et al. We had to change to single beds because I itch in the night’: a qualitative study of the experiences, attitudes and approaches to coping of patients with cutaneous T-cell lymphoma. Br J Dermatol. 2015 Jul;173(1):83–92.

 PubMed Web of Science ®Google Scholar

Bouwhuis SA, Gonzalez-Arriaza HL, McEvoy MT, et al. Physical and mental health survey of 20 patients with Sezary syndrome using the medical outcomes study 36-item short-form health survey. J Eur Acad Dermatol Venereol. 2003 Nov;17(6):724–725.

 PubMed Web of Science ®Google Scholar

Demierre MF, Tien A, Miller D. Health-related quality-of-life assessment in patients with cutaneous T-cell lymphoma. Arch Dermatol. 2005 Mar;141(3):325–330.

 PubMed Web of Science ®Google Scholar

Demierre MF, Gan S, Jones J, et al. Significant impact of cutaneous T-cell lymphoma on patients’ quality of life: results of a 2005 national cutaneous lymphoma foundation survey. Cancer. 2006 Nov 15;107(10):2504–2511.

 PubMed Web of Science ®Google Scholar

Demierre MF, Ferzli P, Miller D. Measuring HRQOL in patients with cutaneous T-cell lymphoma undergoing therapy with oral bexarotene and extracorporeal photopheresis. Arch Dermatol. 2007 May;143(5):659–661.

 PubMedGoogle Scholar

Porkert S, Lehner-Baumgartner E, Knobler R, et al. J-04. Assessment of QoL, illness perception, and illness behavior in 92 patients with primary cutaneous lymphoma. Presented at the 3rd World Congress of Cutaneous Lymphomas, New York, NY; 2016 Oct 26–28.

 Google Scholar

Prince HM, Dummer R, Whittaker S, et al. Patient-reported outcomes and quality of life in patients with cutaneous T cell lymphoma: results from the phase 3 ALCANZA study [conference abstract]. Hematol Oncol. 2017 June;35(Supplement 2):247–248.

 Google Scholar

Prince HM, Kim YH, Horwitz SM, et al. Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017 Jun 06;390(10094):555–566.

 PubMed Web of Science ®Google Scholar

Sampogna F, Frontani M, Baliva G, et al. Quality of life and psychological distress in patients with cutaneous lymphoma. Br J Dermatol. 2009 Apr;160(4):815–822.

 PubMed Web of Science ®Google Scholar

Talpur R, Wieser I, Wang C, et al. Evaluation of health related questionnaire among mycosis fungoides and lymphomatoid papulosis. Blood. 2015;126(23):5603.

 Web of Science ®Google Scholar

Talpur R, Wieser I, Wang C, et al. Evaluation of health related questionnaire among mycosis fungoides and lymphomatoid papulosis. J Am Acad Dermatol. 2016;74(5):AB117.

 Web of Science ®Google Scholar

Vij A, Duvic M. Prevalence and severity of pruritus in cutaneous T cell lymphoma. Int J Dermatol. 2012 Aug;51(8):930–934.

 PubMed Web of Science ®Google Scholar

Wright A, Wijeratne A, Hung T, et al. Prevalence and severity of pruritus and quality of life in patients with cutaneous T-cell lymphoma. J Pain Symptom Manage. 2013 Jan;45(1):114–119.

 PubMed Web of Science ®Google Scholar