Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician’s choice in cutaneous T-cell lymphoma: final data

Horwitz, Steven M.; Scarisbrick, Julia; Dummer, Reinhard; Whittaker, Sean; Duvic, Madeleine; Kim, Youn H; Quaglino, Pietro; Zinzani, Pier Luigi; Bechter, Oliver; Eradat, Herbert; Pinter‐Brown, Lauren; Akilov, Oleg E.; Geskin, Larisa J.; Sanches, José Antônio; Ortiz‐Romero, Pablo L.; Weichenthal, Michael; Fisher, David C.; Walewski, Jan; Trotman, Judith; Taylor, Kerry; Dalle, Stéphane; Stadler, Rudolf; Lisano, Julie; Bunn, Veronica; Little, Meredith; Prince, H. Miles

doi:10.1182/bloodadvances.2021004710

Cited by 51 publications

(44 citation statements)

References 22 publications

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“…Peripheral neuropathy of any grade was observed in 67% of patients (44/66) and grade 3 peripheral neuropathy was observed in 9% (6/66) in the BV group. None had grade 4 peripheral neuropathy; 86% (38/44) of patients with peripheral neuropathy had complete resolution (26/44) or improvement to grade 1–2 (12/44) 39 . In Japan, BV is approved for CD30‐positive PTCL at the dose of 1.8 mg/kg combined with CHP for 21‐day cycles in the first‐line setting or as monotherapy at 1.8 mg/kg for 21‐day cycles in the relapsed or refractory setting.…”

Section: Current and Emerging Therapies For Cutaneous Lymphomamentioning

confidence: 99%

“…None had grade 4 peripheral neuropathy; 86% (38/44) of patients with peripheral neuropathy had complete resolution (26/44) or improvement to grade 1-2 (12/44). 39 In Japan, BV is approved for CD30-positive PTCL at the dose of 1.8 mg/kg combined with CHP for 21-day cycles in the first-line setting or as monotherapy at 1.8 mg/kg for 21-day cycles in the relapsed or refractory setting. BV has not been approved for CTCL in Japan.…”

Section: Brentuximab Vedotinmentioning

confidence: 99%

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Current treatment strategies and emerging therapies for cutaneous lymphoma

Yonekura

2021

The Journal of Dermatology

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Primary cutaneous lymphomas are defined as non-Hodgkin lymphomas presenting in the skin with no evidence of extracutaneous disease at the time of diagnosis. Primary cutaneous lymphoma includes a heterogeneous group of cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL). 1 In Japan, 74.9% of primary cutaneous lymphomas are CTCL, which is much higher than the proportion of CBCL (21.1%). Among CTCL, mycosis fungoides (MF) accounts for the majority at 48.0%, followed by primary cutaneous CD30-positive lymphoproliferative disorders (9.4%), adult T-cell leukemia/lymphoma (ATL, 8.5%) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS, 6.5%). 2 In recent years, many new therapeutic agents have been developed to treat cutaneous lymphomas, especially CTCL. Some of these agents were developed in Japan or approved in Japan prior to approval in Europe or the USA. Therefore, many therapeutic agents are currently available in Japan.This review summarizes the current treatment strategies for cutaneous lymphomas, especially CTCL, and emerging therapies for MF, Sézary syndrome (SS), primary cutaneous anaplastic large cell lymphoma (pcALCL), ATL, and CBCL. | CURRENT THER APEUTI C S TR ATEG IE S FOR CUTANEOUS LYMPHOMAPreviously, for early stage MF or SS, topical corticosteroids, ultraviolet (UV) irradiation, oral etretinate, or a combination thereof, was initially used. In resistant cases, interferon (IFN) was administered. Single-agent or combination chemotherapy was selected for advanced disease. Local radiotherapy (RT) was performed for local tumors. Over the last decade, several new agents have been introduced, which has expanded treatment options.Recently, topical therapy or UV irradiation, which are skindirected therapies (SDT), has been selected as initial treatment for early stage MF or SS. RT is a type of SDT that is used to treat treatment-resistant plaques and tumors. SDT is used in early stages and also in advanced stages in combination with systemic therapies.

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Section: Current and Emerging Therapies For Cutaneous Lymphomamentioning

confidence: 99%

Section: Brentuximab Vedotinmentioning

confidence: 99%

Current treatment strategies and emerging therapies for cutaneous lymphoma

Yonekura

2021

The Journal of Dermatology

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“…Given the impaired patient immunity, increasing the anti-tumor response by immunotherapy is a fundamental and logical approach to combating this cancer and has revolutionized the treatment landscape for many CTCL patients. Monoclonal antibody (mAb) treatment has been the most promising therapy, as indicated by its approval from the Food and Drug Administration for the treatment of advancedstage CTCL (4)(5)(6)(7). However, toxicities associated with mAb/drug conjugation, limited tumor penetration, and high relapse rates occur in most treated patients (8), raising major hurdles to mAb targeted drug therapy.…”

Section: Introductionmentioning

confidence: 99%

CAR-T cell development for Cutaneous T cell Lymphoma: current limitations and potential treatment strategies

Evtimov²,

Jenkin

et al. 2022

Front. Immunol.

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Chimeric antigen receptor (CAR)-T therapy has demonstrated remarkable outcomes for B cell malignancies, however, its application for T cell lymphoma, particularly cutaneous T cell lymphoma (CTCL), has been limited. Barriers to effective CAR-T cell therapy in treating CTCL include T cell aplasia in autologous transplants, CAR-T product contamination with leukemic T cells, CAR-T fratricide (when the target antigen is present on normal T cells), and tumor heterogeneity. To address these critical challenges, innovative CAR engineering by targeting multiple antigens to strike a balance between efficacy and safety of the therapy is necessary. In this review, we discuss the current obstacles to CAR-T cell therapy and highlight potential targets in treating CTCL. Looking forward, we propose strategies to develop more powerful dual CARs that are advancing towards the clinic in CTCL therapy.

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“…Additional data from clinical trials, as well as real-world evidence of HDACi efficacy remain conflicting with overall response rates (ORR) 6-40% and time to next treatment (TTNT) of 3-4 months ( 18 , 19 ). On the other hand, BV, an anti-CD30 Ab-drug conjugate, showed convincingly superior results with ORR of 55% in R/R CTCL and MF patients when compared to bexarotene or LD-MTX in the phase III ALCANZA trial and was approved by both, FDA and EMA ( 20 – 22 ). Similarly, MOGA, a monoclonal antibody targeting C-C chemokine receptor type 4 (CCR4), showed significantly better responses when compared to vorinostat and was approved by FDA and EMA ( 23 – 26 ).…”

Section: Introductionmentioning

confidence: 99%

Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience

et al. 2022

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Cutaneous T-cell lymphomas (CTCL) represent rare non-Hodgkin lymphomas (NHL) with an incidence less than 1 per 100,000 inhabitants. The most common type of CTCL is mycosis fungoides (MF), which represents approximately 60% of all CTCL, followed by Sézary syndrome (SS), approximately 5%. We retrospectively analyzed the outcome of 118 patients with MF (n=96) and SS (n=22) treated between the years 1998 and 2021 at the Charles University General Hospital in Prague, Czech Republic. The ratio between men and women was 1.2:1 (62 men, and 56 women). The median age at diagnosis was 62 years (23 to 92 years). From the MF cohort 48 patients (50% out of MF cohort) presented with advanced stage disease. Ninety patients (77%) received a systemic treatment at any time from the diagnosis; the median number of therapy lines was two. At the time of database lock, the overall survival (OS) of 96 patients with MF reached 17.7 years with the median follow-up 4.0 years. With the median follow-up 2.6 years, the median OS of 22 patients with SS was 3.5 years. The most common type of systemic therapy for MF included low-dose methotrexate (61%), interferon-alpha (58%), bexarotene (28%), and chlorambucil (25%). The most common type of therapy for SS included bexarotene (64%), extracorporeal photopheresis (50%), and interferon-alpha (45%). Only the minority of patients received innovative targeted agents including brentuximab vedotin, mogamulizumab, or pembrolizumab. Besides the retrospective analysis of the CTCL cohort, current standards and future perspectives of selected innovative agents are summarized and discussed. The analyzed cohort represents the largest cohort of CTCL patients in the Czech Republic. Overall, the survival parameters of our CTCL cohort are comparable to those previously published by other groups. In conclusion, our analysis of 118 real world cohort of consecutive CTCL patients treated at the single center confirmed the efficacy of immune response modifiers and underlines the urgent need for ample implementation of innovative agents and their combinations into earlier lines of therapy.

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Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician’s choice in cutaneous T-cell lymphoma: final data

Cited by 51 publications

References 22 publications

Current treatment strategies and emerging therapies for cutaneous lymphoma

Current treatment strategies and emerging therapies for cutaneous lymphoma

CAR-T cell development for Cutaneous T cell Lymphoma: current limitations and potential treatment strategies

Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience

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