The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Ellen J Kim - One of the best experts on this subject based on the ideXlab platform.
-
concomitant use of steroids or phototherapy with Chlormethine gel among patients with mycosis fungoides type cutaneous t cell lymphoma mf ctcl a real world evidence study
European Journal of Cancer, 2021Co-Authors: Christiane Querfeld, Marco Turini, Deval Gor, James T Angello, Chris L Pashos, Ellen J KimAbstract:Background: Chlormethine gel (also known as mechlorethamine) is a skin-directed therapy approved for the treatment of early-stage mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). In previously published data, topical steroids and phototherapy were found to be commonly used by patients treated with Chlormethine gel. Post-hoc analyses on the PROVe study were carried out to describe the specific treatment sequence and timing of these concomitant therapies and Chlormethine gel in a real-world setting among MF-CTCL patients. Methods: Data analyzed derives from the observational PROVe study using US-based registry of MF-CTCL patients treated with Chlormethine gel and enrolled across 46 centers between March 2015 and October 2018. Patients were followed for up to 2 years after Chlormethine gel initiation. Due to the observational nature of the study, patients had visits at irregular intervals. Information on patient demographics, medical history, clinical characteristics, ongoing treatments for MF-CTCL and response were collected. Concomitant use of Chlormethine gel with topical steroids or phototherapy were assessed using treatment start and stop dates recorded in the registry, and descriptive statistics were calculated. Results: A total of 298 eligible patients were analyzed with a mean ± standard deviation (SD) age of 61±13 years. Approximately 60% were males, 69% had Stage IA/IB and their duration of MF-CTCL was 4.8±6.5 years at Chlormethine gel initiation. A total of 186 (85%) reported concomitant use of topical steroids with Chlormethine gel during the study period. Of these 186 patients, 138 (74%) patients were already using steroids prior to Chlormethine gel initiation, 14 (8%) started Chlormethine gel and steroids on same day and the remaining 34 (18%) added steroids later. A total of 81 (27%) reported concomitant use of phototherapy with Chlormethine gel during the study period. Of these 81 patients, 67 (83%) patients were already on phototherapy prior to Chlormethine gel initiation and the remaining 14 (17%) initiated phototherapy later. Conclusions: Among the patients with concomitant therapies, the majority had started steroids or phototherapy and then added Chlormethine gel. These observations suggest that in real life settings, combination treatments are standard practice as physicians expect improved outcomes with an acceptable tolerability profile.
-
maintenance therapy with Chlormethine gel among patients with mycosis fungoides type cutaneous t cell lymphoma mf ctcl a real world evidence study
European Journal of Cancer, 2021Co-Authors: Christiane Querfeld, Marco Turini, Deval Gor, James T Angello, Chris L Pashos, Ellen J KimAbstract:Background: Chlormethine gel is a skin-directed therapy approved in US for daily treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). Based on a previous study it has been observed that the alternative treatment schedules and the schedule changes may benefit patients by improving tolerability and response to treatment [ 1 ]. This study was carried out to better understand schedule changes before and after achieving partial response (PR) and effect of maintenance therapy i.e., continuing treatment with Chlormethine gel after achieving PR, in a real-world setting among MF-CTCL patients. Methods: Data is derived from the observational PROVe study using US-based registry of MF-CTCL patients treated with Chlormethine gel in combination with other treatments between March 2015 and October 2018. Patients were enrolled across 46 centers and were followed for up to 2 years. Information on patient demographics, clinical characteristics, treatments received for MF-CTCL (including Chlormethine gel, topical steroids, phototherapy, radiation therapy, chemotherapy, retinoids and other topical). Responses were collected at enrollment and ongoing visits with no specific visit schedules or clinical assessments due to expected variability in practice patterns. Episodes of treatments with Chlormethine gel with start date, stop date and schedule changes were recorded and analyzed. Partial response (PR) was defined as either ≥50% improvement in body surface area (BSA) at least once from gel initiation to the end of study participation or based on the clinical assessment of the physician. For those who achieved PR and following the date of PR, deepening response was defined as achieving either ≥10% additional improvement in BSA (i.e., 60% or more improvement in BSA after achieving 50% improvement at the time of PR) or achieving complete response based on the clinical assessment by physician. Descriptive statistics were reported for schedule changes and maintenance therapy with Chlormethine gel. Results: Of 298 eligible patients with mean age 61±13 years, 60% were males, and 69% had clinical stage IA/IB. A total of 222 (75%) patients achieved PR following Chlormethine gel initiation and during study period. Of these 222, 81% patients did not change their schedule prior to achieving PR and 61% were on a daily schedule immediately prior to PR. Of 203 patients receiving maintenance Chlormethine gel post PR, 153 (75%) maintained, 29 (14%) reduced and 24 (12%) increased their dosing schedule in the post-PR period as compared to their schedule prior to PR. Of these 203, 53 (26%) later achieved deepening response. Conclusions: 75% of the patients received maintenance therapy with Chlormethine gel in combination with other therapies and continued with the same schedule after PR. The study results suggest that continuing maintenance therapy and adjusting Chlormethine gel dosing schedule may contribute to deepen treatment responses.
-
Chlormethine Gel for the Treatment of Skin Lesions in All Stages of Mycosis Fungoides Cutaneous T-Cell Lymphoma: A Narrative Review and International Experience
Dermatology and Therapy, 2021Co-Authors: Larisa J Geskin, Martine Bagot, Emmilia Hodak, Ellen J KimAbstract:Mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma, is a disease typically with an indolent course that is initially characterized by localized patches and plaques. In the early stages of the disease, treatment involves skin-directed therapies (SDTs) such as topical corticosteroids and retinoids. Chlormethine gel (also known as mechlorethamine) was the first SDT purposely developed to treat MF and is currently endorsed by international guidelines for the treatment of adult patients with MF as a first-line therapy. While Chlormethine is an efficacious therapy, its usage may be complicated by the development of cutaneous reactions at the sites of application. Herein, we discuss the supportive guidelines for MF and the suitability of Chlormethine as a therapeutic option in patients with MF. In addition, we present real-world experience on the use of Chlormethine gel from clinics in the USA, Israel, and France with the aim of demonstrating the efficacy of Chlormethine gel in routine clinical practice and outlining strategies that are being used to manage emergent cutaneous reactions.
-
the prove study us real world experience with Chlormethine mechlorethamine gel in combination with other therapies for patients with mycosis fungoides cutaneous t cell lymphoma
American Journal of Clinical Dermatology, 2021Co-Authors: Ellen J Kim, Christiane Querfeld, James T Angello, Joan Guitart, Michael Girardi, Amy Musiek, Oleg E Akilov, William L Bailey, Larisa J GeskinAbstract:Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on Chlormethine gel are lacking. Our objective was to analyze the effect of Chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. This prospective, observational study enrolled adult patients actively using Chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA–IB disease receiving Chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (Chlormethine + topical corticosteroids + other) and 45.1% (patients receiving Chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (Chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. This real-world study confirmed that Chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.
-
evaluating the treatment patterns of Chlormethine mechlorethamine gel in patients with stage i iia mycosis fungoides by time reanalysis of a randomized controlled phase 2 study
Clinical Lymphoma Myeloma & Leukemia, 2021Co-Authors: Larisa J Geskin, James T Angello, Ellen J Kim, Youn H KimAbstract:Abstract Background The pivotal 201 Study investigated Chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was not inferior to Chlormethine ointment. However, overall response rates do not provide information about response patterns. The study objective was to assess the value of by-time analysis of clinical response data in visualizing response over time. Methods This post hoc analysis re-evaluated Chlormethine efficacy using a by-time approach that investigated the trend to treatment response and permitted assessment of response, both monthly between 1 and 6 months, and once every 2 months between 7 and 12 months, over the course of 1 year. In addition, very good partial response was redefined as a ≥ 75% response. Results By-time analyses of Composite Assessment of Index Lesion Severity (CAILS) and modified severity-weighted assessment tool (mSWAT) showed response rates at 1 month (respectively, 8.5% and 5.9%) that increased over time to peak at 10 months (78.9% and 54.4%). Early, intermittent, and late response patterns were observed. In total, 32.5% of patients experienced very good partial response over 2 consecutive visits, indicating that ∼ 33% of patients could expect to have very good to complete response within 1 year. Conclusion By-time analysis for clinical response provides complementary information to traditional overall response rate data regarding response peak time and changes over time.
Larisa J Geskin - One of the best experts on this subject based on the ideXlab platform.
-
management of mycosis fungoides with topical Chlormethine mechlorethamine gel a columbia university cutaneous lymphoma center experience
Acta Dermato-venereologica, 2021Co-Authors: Tiffany J Garciasaleem, Connor Stonesifer, Alexandra E Khaleel, Larisa J GeskinAbstract:Mycosis fungoides is a type of cutaneous T-cell lymphoma, which accounts for the majority of cases of cutaneous T-cell lymphoma. Mycosis fungoides can be classified as early-stage (IA-IIA) or late-stage (IIB or greater) disease. In early-stage mycosis fungoides, skin-directed therapies are commonly used to manage the disease. Chlormethine, or mechlorethamine, is a topical chemotherapeutic, which has been in use for over 60 years. In 2013, the US Food and Drug Administration approved Chlormethine/mechlorethamine gel (Valchlor®) for treatment of stage IA and IB mycosis fungoides. Chlormethine/mechlorethamine gel is an effective therapy; however, its use may be limited by the development of adverse cutaneous reactions. Off-label dosing modifications, as well as co-administration of topical steroids and an aggressive moisturization regimen, can be used to reduce these side-effects. We report here 4 cases of mycosis fungoides treated with Chlormethine/mechlorethamine gel at the Comprehensive Skin Cancer Center at Columbia University Irving Medical Center, which provide insights into the use of this therapy in clinical practice.
-
Chlormethine Gel for the Treatment of Skin Lesions in All Stages of Mycosis Fungoides Cutaneous T-Cell Lymphoma: A Narrative Review and International Experience
Dermatology and Therapy, 2021Co-Authors: Larisa J Geskin, Martine Bagot, Emmilia Hodak, Ellen J KimAbstract:Mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma, is a disease typically with an indolent course that is initially characterized by localized patches and plaques. In the early stages of the disease, treatment involves skin-directed therapies (SDTs) such as topical corticosteroids and retinoids. Chlormethine gel (also known as mechlorethamine) was the first SDT purposely developed to treat MF and is currently endorsed by international guidelines for the treatment of adult patients with MF as a first-line therapy. While Chlormethine is an efficacious therapy, its usage may be complicated by the development of cutaneous reactions at the sites of application. Herein, we discuss the supportive guidelines for MF and the suitability of Chlormethine as a therapeutic option in patients with MF. In addition, we present real-world experience on the use of Chlormethine gel from clinics in the USA, Israel, and France with the aim of demonstrating the efficacy of Chlormethine gel in routine clinical practice and outlining strategies that are being used to manage emergent cutaneous reactions.
-
the prove study us real world experience with Chlormethine mechlorethamine gel in combination with other therapies for patients with mycosis fungoides cutaneous t cell lymphoma
American Journal of Clinical Dermatology, 2021Co-Authors: Ellen J Kim, Christiane Querfeld, James T Angello, Joan Guitart, Michael Girardi, Amy Musiek, Oleg E Akilov, William L Bailey, Larisa J GeskinAbstract:Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on Chlormethine gel are lacking. Our objective was to analyze the effect of Chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. This prospective, observational study enrolled adult patients actively using Chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA–IB disease receiving Chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (Chlormethine + topical corticosteroids + other) and 45.1% (patients receiving Chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (Chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. This real-world study confirmed that Chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.
-
evaluating the treatment patterns of Chlormethine mechlorethamine gel in patients with stage i iia mycosis fungoides by time reanalysis of a randomized controlled phase 2 study
Clinical Lymphoma Myeloma & Leukemia, 2021Co-Authors: Larisa J Geskin, James T Angello, Ellen J Kim, Youn H KimAbstract:Abstract Background The pivotal 201 Study investigated Chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was not inferior to Chlormethine ointment. However, overall response rates do not provide information about response patterns. The study objective was to assess the value of by-time analysis of clinical response data in visualizing response over time. Methods This post hoc analysis re-evaluated Chlormethine efficacy using a by-time approach that investigated the trend to treatment response and permitted assessment of response, both monthly between 1 and 6 months, and once every 2 months between 7 and 12 months, over the course of 1 year. In addition, very good partial response was redefined as a ≥ 75% response. Results By-time analyses of Composite Assessment of Index Lesion Severity (CAILS) and modified severity-weighted assessment tool (mSWAT) showed response rates at 1 month (respectively, 8.5% and 5.9%) that increased over time to peak at 10 months (78.9% and 54.4%). Early, intermittent, and late response patterns were observed. In total, 32.5% of patients experienced very good partial response over 2 consecutive visits, indicating that ∼ 33% of patients could expect to have very good to complete response within 1 year. Conclusion By-time analysis for clinical response provides complementary information to traditional overall response rate data regarding response peak time and changes over time.
Christiane Querfeld - One of the best experts on this subject based on the ideXlab platform.
-
concomitant use of steroids or phototherapy with Chlormethine gel among patients with mycosis fungoides type cutaneous t cell lymphoma mf ctcl a real world evidence study
European Journal of Cancer, 2021Co-Authors: Christiane Querfeld, Marco Turini, Deval Gor, James T Angello, Chris L Pashos, Ellen J KimAbstract:Background: Chlormethine gel (also known as mechlorethamine) is a skin-directed therapy approved for the treatment of early-stage mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). In previously published data, topical steroids and phototherapy were found to be commonly used by patients treated with Chlormethine gel. Post-hoc analyses on the PROVe study were carried out to describe the specific treatment sequence and timing of these concomitant therapies and Chlormethine gel in a real-world setting among MF-CTCL patients. Methods: Data analyzed derives from the observational PROVe study using US-based registry of MF-CTCL patients treated with Chlormethine gel and enrolled across 46 centers between March 2015 and October 2018. Patients were followed for up to 2 years after Chlormethine gel initiation. Due to the observational nature of the study, patients had visits at irregular intervals. Information on patient demographics, medical history, clinical characteristics, ongoing treatments for MF-CTCL and response were collected. Concomitant use of Chlormethine gel with topical steroids or phototherapy were assessed using treatment start and stop dates recorded in the registry, and descriptive statistics were calculated. Results: A total of 298 eligible patients were analyzed with a mean ± standard deviation (SD) age of 61±13 years. Approximately 60% were males, 69% had Stage IA/IB and their duration of MF-CTCL was 4.8±6.5 years at Chlormethine gel initiation. A total of 186 (85%) reported concomitant use of topical steroids with Chlormethine gel during the study period. Of these 186 patients, 138 (74%) patients were already using steroids prior to Chlormethine gel initiation, 14 (8%) started Chlormethine gel and steroids on same day and the remaining 34 (18%) added steroids later. A total of 81 (27%) reported concomitant use of phototherapy with Chlormethine gel during the study period. Of these 81 patients, 67 (83%) patients were already on phototherapy prior to Chlormethine gel initiation and the remaining 14 (17%) initiated phototherapy later. Conclusions: Among the patients with concomitant therapies, the majority had started steroids or phototherapy and then added Chlormethine gel. These observations suggest that in real life settings, combination treatments are standard practice as physicians expect improved outcomes with an acceptable tolerability profile.
-
maintenance therapy with Chlormethine gel among patients with mycosis fungoides type cutaneous t cell lymphoma mf ctcl a real world evidence study
European Journal of Cancer, 2021Co-Authors: Christiane Querfeld, Marco Turini, Deval Gor, James T Angello, Chris L Pashos, Ellen J KimAbstract:Background: Chlormethine gel is a skin-directed therapy approved in US for daily treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). Based on a previous study it has been observed that the alternative treatment schedules and the schedule changes may benefit patients by improving tolerability and response to treatment [ 1 ]. This study was carried out to better understand schedule changes before and after achieving partial response (PR) and effect of maintenance therapy i.e., continuing treatment with Chlormethine gel after achieving PR, in a real-world setting among MF-CTCL patients. Methods: Data is derived from the observational PROVe study using US-based registry of MF-CTCL patients treated with Chlormethine gel in combination with other treatments between March 2015 and October 2018. Patients were enrolled across 46 centers and were followed for up to 2 years. Information on patient demographics, clinical characteristics, treatments received for MF-CTCL (including Chlormethine gel, topical steroids, phototherapy, radiation therapy, chemotherapy, retinoids and other topical). Responses were collected at enrollment and ongoing visits with no specific visit schedules or clinical assessments due to expected variability in practice patterns. Episodes of treatments with Chlormethine gel with start date, stop date and schedule changes were recorded and analyzed. Partial response (PR) was defined as either ≥50% improvement in body surface area (BSA) at least once from gel initiation to the end of study participation or based on the clinical assessment of the physician. For those who achieved PR and following the date of PR, deepening response was defined as achieving either ≥10% additional improvement in BSA (i.e., 60% or more improvement in BSA after achieving 50% improvement at the time of PR) or achieving complete response based on the clinical assessment by physician. Descriptive statistics were reported for schedule changes and maintenance therapy with Chlormethine gel. Results: Of 298 eligible patients with mean age 61±13 years, 60% were males, and 69% had clinical stage IA/IB. A total of 222 (75%) patients achieved PR following Chlormethine gel initiation and during study period. Of these 222, 81% patients did not change their schedule prior to achieving PR and 61% were on a daily schedule immediately prior to PR. Of 203 patients receiving maintenance Chlormethine gel post PR, 153 (75%) maintained, 29 (14%) reduced and 24 (12%) increased their dosing schedule in the post-PR period as compared to their schedule prior to PR. Of these 203, 53 (26%) later achieved deepening response. Conclusions: 75% of the patients received maintenance therapy with Chlormethine gel in combination with other therapies and continued with the same schedule after PR. The study results suggest that continuing maintenance therapy and adjusting Chlormethine gel dosing schedule may contribute to deepen treatment responses.
-
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
Dermatology, 2021Co-Authors: Christiane Querfeld, Julia Scarisbrick, Chalid Assaf, Emmanuella Guenova, M Bagot, Pablo L Ortizromero, Pietro Quaglino, Erminio Bonizzoni, Emmilia HodakAbstract:BACKGROUND Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Patients can be treated using Chlormethine gel, a skin-directed therapy developed and approved for MF. In the randomized, controlled 201 trial, Chlormethine gel was found to be noninferior to equal-strength Chlormethine ointment. However, there remains a need to gain more insight into outcome measures after treatment. OBJECTIVE The aim of this study was to further investigate the potential of Chlormethine gel treatment through a novel post hoc analysis of the 201 trial data (NCT00168064). METHODS Patients were randomized to Chlormethine gel or ointment; response assessments included Composite Assessment of Index Lesion Severity (CAILS) and total body surface area (BSA). In this post hoc analysis, additional subgroup response analyses were performed for stage IA/IB-IIA MF. Very good partial response (75 to <100% improvement) was included as an additional response category. Time to response and overall response trends were determined. Finally, multivariate time-to-event analyses were performed to determine whether associations were observed between treatment frequency, response, and adverse events. RESULTS Response rates were significantly higher for patients with stage IA MF for CAILS (intent-to-treat [p = 0.0014] and efficacy-evaluable [EE; p = 0.0036] populations) and BSA (EE population [p = 0.0488]) treated with gel versus ointment. Time to first CAILS response and response trends were better for all-stage gel-treated patients overall. No association was seen between treatment frequency and response or occurrence of adverse events at the following visit. An association was observed between the occurrence of contact dermatitis and improved clinical response at the next visit (p = 0.0001). CONCLUSION This post hoc analysis shows that treatment with Chlormethine gel may result in higher and faster response rates compared with Chlormethine ointment, which confirms and expands results reported in the original analysis. The incidence of contact dermatitis may potentially be a prognostic indicator for clinical response; this needs to be confirmed in a larger population.
-
the prove study us real world experience with Chlormethine mechlorethamine gel in combination with other therapies for patients with mycosis fungoides cutaneous t cell lymphoma
American Journal of Clinical Dermatology, 2021Co-Authors: Ellen J Kim, Christiane Querfeld, James T Angello, Joan Guitart, Michael Girardi, Amy Musiek, Oleg E Akilov, William L Bailey, Larisa J GeskinAbstract:Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on Chlormethine gel are lacking. Our objective was to analyze the effect of Chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. This prospective, observational study enrolled adult patients actively using Chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA–IB disease receiving Chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (Chlormethine + topical corticosteroids + other) and 45.1% (patients receiving Chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (Chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. This real-world study confirmed that Chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.
-
a little experience goes a long way Chlormethine mechlorethamine treatment duration as a function of clinician level patient volume for mycosis fungoides cutaneous t cell lymphoma mf ctcl a retrospective cohort study
Frontiers of Medicine in China, 2021Co-Authors: Christiane Querfeld, James T Angello, Theresa R Pacheco, Bradley M Haverkos, Gary Binder, Brian PoligoneAbstract:Topical Chlormethine yields high response rates in mycosis fungoides cutaneous T-cell lymphoma with early discontinuation often attributed to skin reactions. We evaluated over 4,000 patients and found an association of clinician case volume with treatment duration and early discontinuation of Chlormethine gel. The minority of clinicians with high patient volume markedly outperformed clinicians with only few patients on both outcome parameters, yet case volume as low as five patients seemed to mark a threshold for avoiding early discontinuation of treatment regimen.
James T Angello - One of the best experts on this subject based on the ideXlab platform.
-
concomitant use of steroids or phototherapy with Chlormethine gel among patients with mycosis fungoides type cutaneous t cell lymphoma mf ctcl a real world evidence study
European Journal of Cancer, 2021Co-Authors: Christiane Querfeld, Marco Turini, Deval Gor, James T Angello, Chris L Pashos, Ellen J KimAbstract:Background: Chlormethine gel (also known as mechlorethamine) is a skin-directed therapy approved for the treatment of early-stage mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). In previously published data, topical steroids and phototherapy were found to be commonly used by patients treated with Chlormethine gel. Post-hoc analyses on the PROVe study were carried out to describe the specific treatment sequence and timing of these concomitant therapies and Chlormethine gel in a real-world setting among MF-CTCL patients. Methods: Data analyzed derives from the observational PROVe study using US-based registry of MF-CTCL patients treated with Chlormethine gel and enrolled across 46 centers between March 2015 and October 2018. Patients were followed for up to 2 years after Chlormethine gel initiation. Due to the observational nature of the study, patients had visits at irregular intervals. Information on patient demographics, medical history, clinical characteristics, ongoing treatments for MF-CTCL and response were collected. Concomitant use of Chlormethine gel with topical steroids or phototherapy were assessed using treatment start and stop dates recorded in the registry, and descriptive statistics were calculated. Results: A total of 298 eligible patients were analyzed with a mean ± standard deviation (SD) age of 61±13 years. Approximately 60% were males, 69% had Stage IA/IB and their duration of MF-CTCL was 4.8±6.5 years at Chlormethine gel initiation. A total of 186 (85%) reported concomitant use of topical steroids with Chlormethine gel during the study period. Of these 186 patients, 138 (74%) patients were already using steroids prior to Chlormethine gel initiation, 14 (8%) started Chlormethine gel and steroids on same day and the remaining 34 (18%) added steroids later. A total of 81 (27%) reported concomitant use of phototherapy with Chlormethine gel during the study period. Of these 81 patients, 67 (83%) patients were already on phototherapy prior to Chlormethine gel initiation and the remaining 14 (17%) initiated phototherapy later. Conclusions: Among the patients with concomitant therapies, the majority had started steroids or phototherapy and then added Chlormethine gel. These observations suggest that in real life settings, combination treatments are standard practice as physicians expect improved outcomes with an acceptable tolerability profile.
-
maintenance therapy with Chlormethine gel among patients with mycosis fungoides type cutaneous t cell lymphoma mf ctcl a real world evidence study
European Journal of Cancer, 2021Co-Authors: Christiane Querfeld, Marco Turini, Deval Gor, James T Angello, Chris L Pashos, Ellen J KimAbstract:Background: Chlormethine gel is a skin-directed therapy approved in US for daily treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). Based on a previous study it has been observed that the alternative treatment schedules and the schedule changes may benefit patients by improving tolerability and response to treatment [ 1 ]. This study was carried out to better understand schedule changes before and after achieving partial response (PR) and effect of maintenance therapy i.e., continuing treatment with Chlormethine gel after achieving PR, in a real-world setting among MF-CTCL patients. Methods: Data is derived from the observational PROVe study using US-based registry of MF-CTCL patients treated with Chlormethine gel in combination with other treatments between March 2015 and October 2018. Patients were enrolled across 46 centers and were followed for up to 2 years. Information on patient demographics, clinical characteristics, treatments received for MF-CTCL (including Chlormethine gel, topical steroids, phototherapy, radiation therapy, chemotherapy, retinoids and other topical). Responses were collected at enrollment and ongoing visits with no specific visit schedules or clinical assessments due to expected variability in practice patterns. Episodes of treatments with Chlormethine gel with start date, stop date and schedule changes were recorded and analyzed. Partial response (PR) was defined as either ≥50% improvement in body surface area (BSA) at least once from gel initiation to the end of study participation or based on the clinical assessment of the physician. For those who achieved PR and following the date of PR, deepening response was defined as achieving either ≥10% additional improvement in BSA (i.e., 60% or more improvement in BSA after achieving 50% improvement at the time of PR) or achieving complete response based on the clinical assessment by physician. Descriptive statistics were reported for schedule changes and maintenance therapy with Chlormethine gel. Results: Of 298 eligible patients with mean age 61±13 years, 60% were males, and 69% had clinical stage IA/IB. A total of 222 (75%) patients achieved PR following Chlormethine gel initiation and during study period. Of these 222, 81% patients did not change their schedule prior to achieving PR and 61% were on a daily schedule immediately prior to PR. Of 203 patients receiving maintenance Chlormethine gel post PR, 153 (75%) maintained, 29 (14%) reduced and 24 (12%) increased their dosing schedule in the post-PR period as compared to their schedule prior to PR. Of these 203, 53 (26%) later achieved deepening response. Conclusions: 75% of the patients received maintenance therapy with Chlormethine gel in combination with other therapies and continued with the same schedule after PR. The study results suggest that continuing maintenance therapy and adjusting Chlormethine gel dosing schedule may contribute to deepen treatment responses.
-
the prove study us real world experience with Chlormethine mechlorethamine gel in combination with other therapies for patients with mycosis fungoides cutaneous t cell lymphoma
American Journal of Clinical Dermatology, 2021Co-Authors: Ellen J Kim, Christiane Querfeld, James T Angello, Joan Guitart, Michael Girardi, Amy Musiek, Oleg E Akilov, William L Bailey, Larisa J GeskinAbstract:Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on Chlormethine gel are lacking. Our objective was to analyze the effect of Chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. This prospective, observational study enrolled adult patients actively using Chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA–IB disease receiving Chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (Chlormethine + topical corticosteroids + other) and 45.1% (patients receiving Chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (Chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. This real-world study confirmed that Chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.
-
evaluating the treatment patterns of Chlormethine mechlorethamine gel in patients with stage i iia mycosis fungoides by time reanalysis of a randomized controlled phase 2 study
Clinical Lymphoma Myeloma & Leukemia, 2021Co-Authors: Larisa J Geskin, James T Angello, Ellen J Kim, Youn H KimAbstract:Abstract Background The pivotal 201 Study investigated Chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was not inferior to Chlormethine ointment. However, overall response rates do not provide information about response patterns. The study objective was to assess the value of by-time analysis of clinical response data in visualizing response over time. Methods This post hoc analysis re-evaluated Chlormethine efficacy using a by-time approach that investigated the trend to treatment response and permitted assessment of response, both monthly between 1 and 6 months, and once every 2 months between 7 and 12 months, over the course of 1 year. In addition, very good partial response was redefined as a ≥ 75% response. Results By-time analyses of Composite Assessment of Index Lesion Severity (CAILS) and modified severity-weighted assessment tool (mSWAT) showed response rates at 1 month (respectively, 8.5% and 5.9%) that increased over time to peak at 10 months (78.9% and 54.4%). Early, intermittent, and late response patterns were observed. In total, 32.5% of patients experienced very good partial response over 2 consecutive visits, indicating that ∼ 33% of patients could expect to have very good to complete response within 1 year. Conclusion By-time analysis for clinical response provides complementary information to traditional overall response rate data regarding response peak time and changes over time.
-
a little experience goes a long way Chlormethine mechlorethamine treatment duration as a function of clinician level patient volume for mycosis fungoides cutaneous t cell lymphoma mf ctcl a retrospective cohort study
Frontiers of Medicine in China, 2021Co-Authors: Christiane Querfeld, James T Angello, Theresa R Pacheco, Bradley M Haverkos, Gary Binder, Brian PoligoneAbstract:Topical Chlormethine yields high response rates in mycosis fungoides cutaneous T-cell lymphoma with early discontinuation often attributed to skin reactions. We evaluated over 4,000 patients and found an association of clinician case volume with treatment duration and early discontinuation of Chlormethine gel. The minority of clinicians with high patient volume markedly outperformed clinicians with only few patients on both outcome parameters, yet case volume as low as five patients seemed to mark a threshold for avoiding early discontinuation of treatment regimen.
Emmanuella Guenova - One of the best experts on this subject based on the ideXlab platform.
-
increased Chlormethine induced dna double stranded breaks in malignant t cells from mycosis fungoides skin lesions
European Journal of Cancer, 2021Co-Authors: Emmanuella Guenova, Yuntsan Chang, Desislava Ignatova, Wolfram Hoetzenecker, Steve Pascolo, Christina FassnachtAbstract:Background: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of extranodal non-Hodgkin’s lymphoma. Mycosis fungoides (MF) is the most common types of CTCL and considered as a malignancy of skin-resident T cells. Chlormethine (CL), also known as mechlorethamine or nitrogen mustard, is a synthetic agent with well-known alkylating capacity. Its topical application has a long tradition in dermatology, as CL-containing products have been used for the treatment of MF since 1940. Recently, a novel CL gel formulation has been approved for the treatment of skin lesions in MF adult patients. Objective: Here we aim to study the impact of CL on malignant skin T cells regarding their susceptibility to treatment, proliferation, DNA double strand breaks and the expression of alkylated-nucleotides-excision genes. Methods: Tumour blood or skin T cells were isolated by magnetic-activated cell (MACS) sorting. Susceptibility to CL exposure was evaluated by MTT assay. Proliferation and DNA double strand breaks upon CL exposure were detected by BrdU proliferation assay and flowcytometry for γH2AX Ser139. Expression of alkylated-nucleotides-excision genes was measured by reverse transcription quantitative PCR (RT-qPCR). Results: While CL exposure in vitro decreased time- and dose-dependently total blood T-cell viability, it did not statistically significantly influence neither blood nor skin T-cell proliferation. Of interest, when acting on skin T cells, CL induce DNA double stranded breaks predominately in the subpopulation of MF clonal malignant skin T cells but not the non-tumoral healthy T cells. Quantitative real-time PCR uncovered that several important genes involved in rescue of alkylated nucleotides were generally decreased in tumor T cells and CL exposure in vitro further significantly decreased the expression of FEN1 and BRCA2, two major alkylated-nucleotides-excision-repair genes. Conclusion: This study sheds light on how CL affects malignant skin T cells from patients with MF and provides additional rationale for considering it as an early and valuable skin-directed treatment option for skin lymphoma.
-
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
Dermatology, 2021Co-Authors: Christiane Querfeld, Julia Scarisbrick, Chalid Assaf, Emmanuella Guenova, M Bagot, Pablo L Ortizromero, Pietro Quaglino, Erminio Bonizzoni, Emmilia HodakAbstract:BACKGROUND Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Patients can be treated using Chlormethine gel, a skin-directed therapy developed and approved for MF. In the randomized, controlled 201 trial, Chlormethine gel was found to be noninferior to equal-strength Chlormethine ointment. However, there remains a need to gain more insight into outcome measures after treatment. OBJECTIVE The aim of this study was to further investigate the potential of Chlormethine gel treatment through a novel post hoc analysis of the 201 trial data (NCT00168064). METHODS Patients were randomized to Chlormethine gel or ointment; response assessments included Composite Assessment of Index Lesion Severity (CAILS) and total body surface area (BSA). In this post hoc analysis, additional subgroup response analyses were performed for stage IA/IB-IIA MF. Very good partial response (75 to <100% improvement) was included as an additional response category. Time to response and overall response trends were determined. Finally, multivariate time-to-event analyses were performed to determine whether associations were observed between treatment frequency, response, and adverse events. RESULTS Response rates were significantly higher for patients with stage IA MF for CAILS (intent-to-treat [p = 0.0014] and efficacy-evaluable [EE; p = 0.0036] populations) and BSA (EE population [p = 0.0488]) treated with gel versus ointment. Time to first CAILS response and response trends were better for all-stage gel-treated patients overall. No association was seen between treatment frequency and response or occurrence of adverse events at the following visit. An association was observed between the occurrence of contact dermatitis and improved clinical response at the next visit (p = 0.0001). CONCLUSION This post hoc analysis shows that treatment with Chlormethine gel may result in higher and faster response rates compared with Chlormethine ointment, which confirms and expands results reported in the original analysis. The incidence of contact dermatitis may potentially be a prognostic indicator for clinical response; this needs to be confirmed in a larger population.