Post hoc Analysis of a Randomized, Controlled, Phase 2 Study to Assess Response Rates with Chlormethine/Mechlorethamine Gel in Patients with Stage ...
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Research Article
Dermatology Received: December 15, 2020
Accepted: March 24, 2021
DOI: 10.1159/000516138 Published online: June 4, 2021
Post hoc Analysis of a Randomized, Controlled,
Phase 2 Study to Assess Response Rates with
Chlormethine/Mechlorethamine Gel in Patients
with Stage IA–IIA Mycosis Fungoides
Christiane Querfeld a Julia J. Scarisbrick b Chalid Assaf c, d
Emmanuella Guenova e, f Martine Bagot g Pablo Luis Ortiz-Romero h
Pietro Quaglino i Erminio Bonizzoni j Emmilia Hodak k
aCity of Hope Cancer Center, Duarte, CA, USA; bUniversity of Birmingham, Birmingham, UK; cDepartment of
Dermatology and Venereology, Helios Klinikum Krefeld, Krefeld, Germany; dAcademic Teaching Hospital of the
University of Aachen, Aachen, Germany; eDepartment of Dermatology, University Hospital Lausanne, Lausanne,
Switzerland; fFaculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland; gDepartment of
Dermatology, AP-HP, Université de Paris, Hôpital Saint-Louis, Paris, France; hHospital 12 de Octubre, Institute I+12,
CIBERONC, Medical School, Universidad Complutense, Madrid, Spain; iDepartment of Medical Sciences, Section of
Dermatology, University of Turin, Turin, Italy; jDepartment of Clinical Sciences and Community, Section of Medical
Statistics, Biometry and Epidemiology, University of Milan, Milan, Italy; kDepartment of Dermatology, Rabin Medical
Center, Beilinson Hospital, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Keywords and total body surface area (BSA). In this post hoc analysis,
Chlormethine gel · Mechlorethamine gel · Mycosis additional subgroup response analyses were performed for
fungoides · Cutaneous T-cell lymphoma · Response rates stage IA/IB–IIA MF. Very good partial response (75 toshows that treatment with chlormethine gel may result in mulation that allows for convenient, simple at-home ad-
higher and faster response rates compared with chlorme- ministration, thereby encouraging patient compliance.
thine ointment, which confirms and expands results report- The pivotal 201 trial, one of the largest randomized,
ed in the original analysis. The incidence of contact dermati- controlled, phase 2/3 studies ever conducted in patients
tis may potentially be a prognostic indicator for clinical re- with MF (n = 260), compared chlormethine gel with
sponse; this needs to be confirmed in a larger population. equal-strength compounded ointment. The primary ef-
© 2021 The Author(s) ficacy endpoint was the Composite Assessment of Index
Published by S. Karger AG, Basel Lesion Severity (CAILS) score, and chlormethine gel met
all prespecified criteria for noninferiority to chlorme-
Introduction thine ointment [11]. CAILS response rates for chlorme-
thine gel were consistently higher than for ointment in
Mycosis fungoides (MF) is the most common form of both the intent-to-treat (ITT) and efficacy-evaluable (EE;
cutaneous T-cell lymphoma, which represents a hetero- patients who were treated for ≥6 months) populations
geneous group of lymphoproliferative diseases [1]. MF is [11].
characterized by malignant T-cell proliferation in the There is still an unmet need to understand the efficacy
skin; these are generally CD4+ memory T cells that ex- and response patterns of chlormethine gel in more detail
press skin-homing receptors [2, 3]. Early stage (IA–IIA) and to evaluate how to best manage patients with MF re-
MF can be difficult to diagnose, and diagnosis is delayed ceiving chlormethine gel. The original study 201 analysis
in the majority of patients (86%) for a median of 36 did not directly compare response rates for gel and oint-
months [4]. ment since it was designed to determine noninferiority of
Treatment for MF is generally focused on control of the gel compared to the ointment only. To provide fur-
cutaneous lesions, preventing disease progression, and ther insight into the potential of chlormethine gel treat-
improving quality of life [5–7]. For patients with early- ment, a set of post hoc analyses was designed. In the orig-
stage disease, international guidelines recommend using inal 201 study analysis, response rates were defined per
skin-directed therapies (SDTs), while for more advanced standard oncology criteria; complete response (CR) was
stages a combination of SDT and systemic therapy is ad- defined as 100% skin clearance, with a CAILS or Modified
vised [5–7], although there is substantial treatment het- Severity-Weighted Assessment Tool (mSWAT) score of
erogeneity in advanced MF [8]. 0, and partial response (PR) as 50 toTable 1. Main outcome measures for the original and post hoc analyses
Original study 201 analysis main outcome measures
Response rates – CAILS and mSWAT scores were calculated at baseline and tumor response was assessed at each visit according to standard oncology
criteria
– Confirmed responses were those observed for at least 2 consecutive visits and at least 4 weeks
– Overall CAILS response rates were compared for patients with stage IA and IB–IIA disease
– Noninferiority of gel to ointment was established
Time to response – The time to first confirmed response was evaluated by Kaplan-Meier analysis for all patients treated with chlormethine gel or
ointment
– Treatment arms were compared using a log-rank statistic
Post hoc analysis main outcome measures
Response rates – CAILS, mSWAT, and BSA* response rates were determined for patients with stage IA and IB–IIA disease
– Each visit was considered as a single time point, excluding the requirement for 2 consecutive visits with response
– Subgroup analyses were performed using GLIMs
Time to response – Patients were recategorized according to CR, VGPR, and PR
– The time to first confirmed response was evaluated by Kaplan-Meier analysis for all patients treated with chlormethine gel or
ointment
– Treatment arms were compared using a log-rank statistic
Response trends – Patients were recategorized according to CR, VGPR, and PR
over time – Longitudinal data analysis was performed using GEE models
Multivariate time- – Associations between frequency of treatment application and occurrence of skin-related AEs (dermatitis) or response, and between
to-event analyses the occurrence of dermatitis and clinical response were assessed
* BSA results were collected in the case report forms in the original 201 study report. AE, adverse event; BSA, body surface area; CAILS, Composite
Assessment of Index Lesion Severity; CR, complete response; GEE, generalized estimating equation; GLIMs, generalized linear models; mSWAT, Modified
Severity-Weighted Assessment Tool; PR, partial response; VGPR, very good partial response.
quency of gel application and adverse events (AEs) or Materials and Methods
CAILS responses, analyses were performed with the aim
Patients and Study Design
of providing useful insights for physicians involved in
The randomized, controlled, observer-blinded, multicenter
treatment management. 201 trial compared daily treatment with 0.02% chlormethine gel to
Consequently, we performed a post hoc analysis of the equal-strength chlormethine ointment in 260 patients with MF.
201 study focused on analyzing the efficacy data in more Study design details have been previously published [11]. The pri-
detail. Different statistical approaches were applied to the mary endpoint of study 201 was response as defined by ≥50% im-
provement in baseline CAILS for 2 or more consecutive visits. Sec-
data, reporting each visit outcome as a separate time
ondary endpoints included ≥50% improvement in mSWAT scores
point. Furthermore, the post hoc analysis compared and the time to CAILS response.
CAILS, mSWAT, and total body surface area (BSA) in- Chlormethine gel or ointment was applied once daily for up to
volvement for patients with stage IA or IB–IIA MF treat- 12 months. In case of skin-related AEs, treatment frequency was
ed with chlormethine gel or ointment. Patients were re- reduced temporarily as per protocol. When patients experienced
grade 3 AEs, treatment frequency could be temporarily reduced or
categorized as having CR, VGPR, or PR and time-trend
suspended. If the AE improved to grade 2 or lower, treatment fre-
analyses were performed to highlight the responses with quency could be increased again as tolerated. When patients expe-
chlormethine gel and ointment. In addition, this post hoc rienced grade 4 AEs, treatment was discontinued until the AE im-
analysis investigated whether associations were observed proved to grade 2 or lower, after which treatment could be restart-
between chlormethine gel treatment frequency and clini- ed at a decreased frequency and increased as tolerated.
Tumor response and AEs were assessed every month between
cal response or the occurrence of any skin-related AEs, or
months 1–6 and every 2 months between months 7–12. Response
between the occurrence of contact dermatitis and re- was assessed using CAILS, mSWAT, and BSA involvement. CAILS
sponse. is a method of index lesion scoring for patch/plaque disease con-
sidering erythema, scaling, plaque elevation, hypo- or hyperpig-
Post hoc Analysis of Response Rates with Dermatology 3
Chlormethine Gel in MF DOI: 10.1159/000516138mentation, and lesion size [16]. For all patients, up to 5 index le- gel and ointment; response was defined as CR only, at least VGPR,
sions were identified at baseline and assessed throughout the or at least PR.
study. The mSWAT is calculated by multiplying the BSA of each
lesion type in 12 different areas of the body with a weighting factor Multivariate Time-to-Event Analysis
(patch = 1, plaque = 2, and tumor = 4) [16]. Total BSA involvement Multivariate time-to-event analyses were employed to test the
can also be determined without weighting factors. association between potential predictors (covariates) and events of
interest that may occur multiple times in the same patient (e.g.,
Statistical Methods occurrence of AEs or response) and were performed using the safe-
The main outcome measures for the original study 201 analysis ty population of the chlormethine gel arm (n = 128). Multivariate
and the post hoc analysis are listed in Table 1. Details of the applied time-to-event data were analyzed using the semiparametric pro-
statistical methods are presented in online supplementary Table S1 portional means model [22] implemented in the PHREG proce-
(see www.karger.com/doi/10.1159/000516138 for all online suppl. dure of SAS software. This statistical model is also able to accom-
material). modate so-called time-dependent covariates (e.g., treatment fre-
quency or occurrence of dermatitis), that is, dynamic covariates
Subgroup Analyses that can change value or status over time within the same patient.
Subgroup analyses for CAILS, mSWAT, and BSA response data Results are reported as hazard ratios with associated 95% confi-
were done for patients with stage IA and stage IB–IIA MF in both dence intervals.
the ITT and EE populations. The response variable used in this
analysis was the proportion of response, defined as PR or better, at
the final study visit. CR was defined as 100% improvement (with a
score of 0), PR as a 50 toTable 2. Clinical response (≥50% improvement in skin score) by MF stage in the original and post hoc analyses of the 201 study data
ITT population EE population
CL gel CL ointment p value CL gel CL ointment p value
CAILS, %
Original analysis*
Stage IA 59.2 40.0 N/A 79.6 56.1 N/A
Stage IB–IIA 57.4 55.4 N/A 73.2 61.1 N/A
Post hoc analysis
Stage IA 79.8 49.2 0.0014 82.3 51.4 0.0036
Stage IB–IIA 77.0 59.6 0.0785 79.5 61.5 0.0697
mSWAT, %
Original analysis*
Stage IA 40.8 36.9 N/A 57.1 48.8 N/A
Stage IB–IIA 55.6 55.4 N/A 70.7 61. 1 N/A
Post hoc analysis
Stage IA 48.9 36.9 0.2422 54.3 38.2 0.1384
Stage IB–IIA 55.2 55.8 0.9554 58.9 57.3 0.8766
BSA, %
Post hoc analysis
Stage IA 49.5 33.2 0.0934 56.4 35.2 0.0488
Stage IB–IIA 47.2 50.3 0.7648 49.4 51.6 0.8368
* The original study 201 analysis was based on noninferiority. BSA, body surface area; CAILS, Composite Assessment of Index Lesion
Severity; CL, chlormethine; EE, efficacy-evaluable; ITT, intent-to-treat; MF, mycosis fungoides; mSWAT, Modified Severity-Weighted
Assessment Tool; N/A, not available.
The post hoc analysis mSWAT response rates were 0.0107; Fig. 1b), in favor of patients treated with chlorme-
higher for stage IA patients treated with chlormethine gel thine gel. The difference in time to response was also sig-
compared with ointment for both the ITT and EE popu- nificant when response was defined as at least PR (p =
lations, although these differences were not significant 0.0419; Fig. 1c).
(Table 2). mSWAT results for patients with stage IB–IIA
were comparable between gel and ointment. Trend Analyses
The post hoc analysis showed that BSA response rates Trend analyses were performed in order to better un-
were higher with chlormethine gel compared with oint- derstand the strength of response to chlormethine gel
ment in patients with stage IA in both the ITT and EE versus ointment. These comparisons take into account
populations. The difference was significant for the EE responses evaluated on all visits rather than requiring re-
population (p = 0.0488; Table 2). sponse to be defined as improvement over 2 consecutive
visits. In the ITT population, responses with chlorme-
Time to Response thine gel were higher than those with chlormethine oint-
When comparing the time to CAILS response between ment (Fig. 2a) and this difference was statistically signifi-
chlormethine gel and ointment in the ITT population, a cant when response was defined as at least VGPR (p =
difference was evident in the time-to-response curves 0.0420) or as at least PR (p = 0.0013). Similar results were
when response was defined as CR only; the time to re- observed in the EE population (Fig. 2b), where the differ-
sponse appeared to be shorter for chlormethine gel-treat- ence between patients treated with gel and ointment was
ed patients, but this difference was not statistically sig- close to significant when response was defined as at least
nificant (p = 0.2678; Fig. 1a). When response was defined VGPR (p = 0.0605), and significant when response was
as at least VGPR, the difference between chlormethine defined as at least PR (p = 0.0030).
gel- and ointment-treated patients was significant (p =
Post hoc Analysis of Response Rates with Dermatology 5
Chlormethine Gel in MF DOI: 10.1159/0005161381.0 CR only
Censored
log-rank p = 0.2678
0.9
Survival
0.8 Treatment arm
Chlormethine ointment
Chlormethine gel
0 2 4 6 8 10
Month
Chlormethine ointment 123 123 116 111 100 90 88 83 83 75 75
a Chlormethine gel 118 118 109 98 93 86 78 74 74 70 70
1.0 At least VGPR
Censored
log-rank p = 0.0107
0.8
Survival
0.6
0.4
0.2
0 2 4 6 8 10
Month
Chlormethine ointment 123 123 112 104 89 79 73 64 64 57 57
b Chlormethine gel 118 118 108 91 81 70 60 50 50 44 44
1.0 At least PR
Censored
log-rank p = 0.0419
0.8
0.6
Survival
0.4
0.2
Fig. 1. Time to first occurrence of Compos-
ite Assessment of Index Lesion Severity 0
(CAILS) response in patients in the intent- 0 2 4 6 8 10
to-treat (ITT) population treated with Month
chlormethine gel or ointment for patients
with complete response (CR) (a), at least Chlormethine ointment 123 123 102 82 64 53 45 37 37 29 29
very good partial response (VGPR) (b), c Chlormethine gel 118 118 99 74 55 45 34 24 24 16 16
and at least partial response (PR) (c).
6 Dermatology Querfeld et al.
DOI: 10.1159/0005161380.25 CR only 0.25 CR only
Treatment
Chlormethine ointment
0.20 Chlormethine gel 0.20
Proportion ± SE
Proportion ± SE
0.15 0.15
0.10 0.10
0.05 0.05
p = 1.00 p = 0.9714
0 0
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10
Month Month
0.55 At least VGPR 0.6 At least VGPR
0.5
0.41
0.4
Proportion ± SE
Proportion ± SE
0.28 0.3
0.2
0.14
0.1
p = 0.042 p = 0.0605
0 0
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10
Month Month
1.0 At least PR 1.0 At least PR
0.8 0.8
Proportion ± SE
Proportion ± SE
0.6 0.6
0.4 0.4
0.2 0.2
p = 0.0013 p = 0.003
0 0
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10
a Month b Month
Fig. 2. Composite Assessment of Index Lesion Severity (CAILS) response trends for patients treated with chlor-
methine gel (dashed line) or ointment (solid line) in the intent-to-treat (a) or efficacy-evaluable populations (b).
CR, complete response; VGPR, very good partial response; PR, partial response; SE, standard error.
Multivariate Time-to-Event Analysis relevant for this post hoc analysis included contact der-
The effect of treatment frequency on the occurrence of matitis, erythema, folliculitis, pruritus, skin hyperpig-
skin-related AEs at each following visit was determined mentation, and skin irritation. The total number of skin-
by comparing patients using chlormethine gel on a daily related AEs that occurred in the analyzed population was
basis with those using it less frequently. Skin-related AEs 64; these occurred in 45 patients in total: 30 (67%) had 1
Post hoc Analysis of Response Rates with Dermatology 7
Chlormethine Gel in MF DOI: 10.1159/0005161381.0
Probability of freedom from adverse events
p = 0.8514
HR: 0.951; 95% CI (0.561, 1.610)
0.8
0.6
0.4
0.2 Treatment application
Every day
Not every day
0
0 2 4 6 8 10
a Month
1.0
p = 0.8850
HR: 0.983; 95% CI (0.776, 1.245)
0.8
Nonresponse probability
0.6
0.4
0.2 Treatment application
Every day
Not every day
0
0 2 4 6 8 10
b Month
1.0
p = 0.0001
HR: 2.281; 95% CI (1.493, 3.484)
0.8
Nonresponse probability
0.6
0.4
Fig. 3. Associations between chlormethine
0.2 Contact dermatitis
gel application frequency and the occur-
Yes
rence of adverse events (a), chlormethine No
gel application frequency and Composite 0
Assessment of Index Lesion Severity 0 2 4 6 8 10
(CAILS) response (b), and the occurrence c Month
of dermatitis and CAILS response (c). HR,
hazard ratio; CI, confidence interval.
8 Dermatology Querfeld et al.
DOI: 10.1159/000516138AE, 11 (24%) had 2 AEs, and 4 (9%) had 3 AEs. Eight could be particularly interesting from a clinical point of
cases of contact dermatitis occurred. The analysis did not view to further define the level of response in MF.
demonstrate an association between the frequency of The efficacy results seen in the current post hoc analy-
chlormethine gel application and the occurrence of skin- sis indicate that there may be a benefit to using chlorme-
related AEs (p = 0.8514; Fig. 3a). The potential effect of thine gel over chlormethine ointment for patients with
application frequency of chlormethine gel on CAILS re- MF. Chlormethine gel may also be easier to apply for pa-
sponse at the following visit was also assessed. The analy- tients. Nonadherence to treatment has been observed
sis did not demonstrate an association between the fre- with chlormethine ointment due to greasiness of oint-
quency of chlormethine gel application and occurrence of ment-based preparations [25, 26]. In contrast, chlorme-
a CAILS response (p = 0.8850; Fig. 3b). Finally, the asso- thine gel is nongreasy and quick to absorb.
ciation between the occurrence of contact dermatitis and The multivariate time-to-event analyses showed that
CAILS response at the following visit was investigated. there was no clear association between treatment fre-
This analysis showed an association between the occur- quency and the development of skin-related AEs or clin-
rence of contact dermatitis and an improved clinical re- ical response at the next visit. This indicates that reducing
sponse at the next visit (p = 0.0001; Fig. 3c). the frequency of chlormethine gel application might not
affect the possibility of developing skin-related AEs. In
addition, it might be possible to be more flexible with
Discussion chlormethine gel treatment schedules, reducing the ap-
plication frequency from once daily on the basis of indi-
The presented post hoc analysis shows that treat- vidual patient characteristics and needs, without impact-
ment with chlormethine gel may result in higher re- ing the efficacy of the treatment. This should be investi-
sponse rates than treatment with chlormethine oint- gated further to determine the effect of reduced treatment
ment in patients with stage IA MF. According to stage frequency on the overall response. The presence of stimu-
stratification, CAILS (ITT and EE populations) and lated T cells in the environment and background inflam-
BSA response rates (EE population) were significantly mation could be partially responsible for no clear asso-
higher for chlormethine gel compared with ointment. ciation existing between lower treatment frequency and
BSA results were collected in the case report forms in occurrence of AEs. This observation also fits with real-
the original 201 study report [11], but had not previ- world evidence from the recent PROVe study, where pa-
ously been reported. We chose to report the BSA re- tients had a greater variation in treatment schedules with
sponse analyses here, as it is an important clinical indi- chlormethine gel than study 201. Even with this dose flex-
cator regularly recorded in clinical practice. A prospec- ibility, patients still had good responses during the PROVe
tive observational study examining real-world study, and the peak of response (67%) was seen after 18
experience with chlormethine gel (PROVe) [23] used months of treatment [27]. In addition, differently from
the percentage change in BSA as a clinical outcome study 201, lower rates of AEs were seen in the PROVe
measure [24]. Overall, the stage stratification data rein- study, although this could partly be due to the different
force the concept that chlormethine gel is a valid first- dose regimen used, and to the concomitant use of corti-
line treatment option, especially for early-stage MF. costeroids in clinical practice, a method employed by cli-
The time to first CAILS response in the ITT popula- nicians to help manage skin reactions [23]. These results
tion was shorter in patients treated with chlormethine gel could suggest that, independently of treatment frequen-
compared with ointment; this difference was significant cy, continued use of chlormethine gel over time may still
when CAILS response was defined as at least VGPR or at be beneficial in many cases [28]. An association was ob-
least PR. The time-trend analyses confirmed that higher served between the occurrence of contact dermatitis at
CAILS response rates were seen over time with chlorme- the previous visit and response at the following visit,
thine gel. which may imply that development of contact dermatitis
PR as defined in the original 201 analysis included a after chlormethine gel treatment may be a predictor of
broad range of responses between 50 andfurther investigation. It will be explored in the REACH Statement of Ethics
study (NCT04218825), which will compare response
Institutional review board approval of the 201 study was ob-
rates in patients with and without skin-related reactions tained at all study sites, and the study complied with Good Clinical
after chlormethine gel application. Future research on the Practice guidelines and the Declaration of Helsinki. All patients
link between contact dermatitis and response should also provided written informed consent prior to enrollment.
analyze the etiology of the dermatitis in more detail.
The current results were analyzed post hoc as well as
found within the context of a controlled clinical trial. Conflict of Interest Statement
Therefore, the data presented here have the limitation of
only referring to the specific criteria of the 201 study, such C. Querfeld: research grant: Celgene; clinical investigator: Cel-
gene, Trillium, miRagen, Bioniz, Kyowa Kirin; advisory board:
as patients not being allowed concomitant treatment, in- Helsinn, miRagen, Bioniz, Trillium, Kyowa Kirin.
cluding corticosteroids; a controlled treatment applica- J.J. Scarisbrick: consultancy: Takeda, Helsinn, Recordati, 4SC,
tion schedule; and limited duration of patient monitoring Kyowa, Mallinckrodt, miRagen; research grant: Kyowa.
(12 months). A real-world study of chlormethine gel us- C. Assaf: advisory board: 4SC, Takeda, Helsinn, Innate Phar-
age has shown that it is often used together with other ma, Recordati Rare Diseases, Kyowa.
E. Guenova: research grants: Helsinn Healthcare SA, Takeda
treatment options and can be used less frequently than Pharmaceutical Co., Ltd.; consultancy: Scailyte AG, Mallinckrodt
once daily [23, 27]. Pharmaceuticals, Kyowa Hakko Kirin Co., Ltd., Novartis, Sanofi.
In conclusion, results from the post hoc analysis of the M. Bagot: scientific advisory board: Helsinn-Recordati, Take-
201 study data described herein suggest that treatment da, Innate Pharma, Kyowa Kirin, Galderma.
with chlormethine gel may result in higher and faster re- P.L. Ortiz-Romero: advisory board: 4SC, Takeda, Actelion, In-
nate Pharma, Recordati Rare Diseases, Kyowa, Helsinn, miRagen;
sponse rates than treatment with chlormethine ointment. patent: PLCG1; research support: Meda (company owned by Via-
These data confirm and expand on the noninferiority re- tris).
sults reported in the original 201 study analysis [11]. P. Quaglino: advisory board: 4SC, Takeda, Actelion, Innate
Moreover, our data suggest that contact dermatitis might Pharma, Recordati Rare Diseases, Kyowa, Therakos.
be a prognostic factor for clinical response to chlorme- E. Bonizzoni: consultancy: Helsinn, Roche, Zambon, Adienne.
E. Hodak: scientific advisory board: Actelion, Helsinn, Recor-
thine gel. Finally, preliminary results indicate that within dati Rare Diseases, Takeda; speakers’ bureau: Helsinn, Rafa, Take-
the present set of analyses, the frequency of gel applica- da.
tion was not directly associated with the incidence of
skin-related AEs (including contact dermatitis) or clini-
cal response; this is an intriguing sign that warrants fur- Funding Sources
ther exploration. While these last results were found
within the limits of a controlled clinical trial, they are an Supported by Helsinn Healthcare SA, who were involved in:
interesting observation that could help improve treat- analysis plan and conduct of the study; collection, management,
data analysis, and interpretation of the data; preparation, review,
ment efficacy for patients with MF. and approval of the manuscript as well as the decision to submit
the manuscript for publication. Writing and editorial assistance
was funded by Helsinn Healthcare SA.
Key Message
Chlormethine gel treatment for mycosis fungoides may result Author Contributions
in higher/faster response rates compared with chlormethine oint-
ment. Concept and design: C. Querfeld, J.J. Scarisbrick, C. Assaf, E.
Guenova, M. Bagot, P.L. Ortiz-Romero, P. Quaglino, E. Bonizzoni,
E. Hodak. Analysis and interpretation of the data: E. Bonizzoni.
Acknowledgements Drafting of the article or critical revision of the article for impor-
tant intellectual content: C. Querfeld, J.J. Scarisbrick, C. Assaf, E.
The authors would like to acknowledge and thank the volun- Guenova, M. Bagot, P.L. Ortiz-Romero, P. Quaglino, E. Bonizzoni,
teers, investigators, and study teams at the centers participating in E. Hodak.
these studies. Editorial and medical writing assistance was pro-
vided by Judith Land, PhD, from Aptitude Health, The Hague, The
Netherlands, funded by Helsinn Healthcare SA. The authors are
fully responsible for all content and editorial decisions for this ar-
ticle.
10 Dermatology Querfeld et al.
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