Treatment Of Cutaneous B-cell Lymphoma Research Articles

Diagnosis and Treatment of Primary Cutaneous B-Cell Lymphomas: State of the Art and Perspectives.

Primary cutaneous B-cell lymphomas are rare entities that develop primarily in the skin. They constitute a heterogeneous group that represents around a quarter of primary cutaneous lymphomas. The 2018 update of the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification differentiates primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma with an indolent course from primary cutaneous diffuse large B-cell lymphoma, leg type with an aggressive behavior. The broad spectrum of clinical presentations and the disease course marked by frequent relapses are diagnostic and therapeutic challenges. The classification of these diseases has been refined in recent years, which allows to better define their immunopathogenesis and specific management. In the present article, we review the main clinico-biological characteristics and the current therapeutic options of these three main subsets. Based on the recent therapeutic advances in nodal B-cell lymphomas, we focus on the development of novel treatment options applicable to primary cutaneous B-cell lymphomas, including targeted therapies, combination treatments and immunotherapeutic approaches, and cover basic, translational and clinical aspects aiming to improve the treatment of cutaneous B-cell lymphomas.

Recent advances in primary cutaneous B-cell lymphomas

In the last decade, there has been considerable debate regarding the classification and terminology of the group of primary cutaneous B-cell lymphomas (CBCLs). With the introduction of the WHO-EORTC classification for cutaneous lymphomas, three main types of CBCLs are recognized: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCLBCL, LT). Epidemiological studies performed on different patient cohorts showed that the CBCL entities described in the WHO-EORTC classification and the 4th WHO classification of tumours of haematopoietic and lymphoid tissues are reproducible worldwide and are clinically relevant, thereby illustrating the clinical usefulness of the WHO-EORTC classification. Furthermore, collaborative studies between the ISCL and EORTC lymphoma group resulted in recommended staging procedures and consensus treatment recommendations for different CBCL subtypes. The advances in the classification, staging procedures and treatment of CBCLs have led to a major improvement in clinical care. The progress in CBCL classification enables molecular studies on well defined groups of patients and facilitates comparison of treatment results between different centres. Recent studies found that intralesional/intravenous rituximab has a therapeutic value in PCFCL and PCMZL with widespread cutaneous lesions and suggest that therapies targeting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway could be helpful in DLBCL, LT.

Prise en charge des lymphomes B cutanés : recommandations du Groupe français d’étude des lymphomes cutanés

To provide recommendations for the treatment of cutaneous B-cell lymphomas (CBCL). Literature review and expert opinions from the French Cutaneous Lymphoma Study Group. Diagnosis of marginal zone BCL (MZ BCL), centrofollicular BCL (CF BCL) or cutaneous large B-cell lymphoma, leg type (CLBCL, LT) is based on combination of clinical signs and histopathological features, together with B-cell clonality analyses whenever possible. Staging relies on straightforward laboratory examinations and imaging, completed in selected cases with bone marrow biopsy. Treatment may be topical, including excision, curative radiotherapy (30Gray) or adjunctive/low dose (4Gray) radiotherapy, topical corticosteroids, interferon or intralesional rituximab; or systemic, using chemotherapy and/or intravenous rituximab. For indolent forms of the disease (MZ CBCL and CF CBCL), curative (30Gray) may be given as first-line treatment in patients with localized lesions or few scattered skin lesions. For more numerous slow-growing lesions with a low tumour burden, simple monitoring with adjunctive ad hoc local treatment of individual lesions is acceptable. For multiple growing lesions, systemic rituximab or chlorambucil may be proposed. Polychemotherapy should only be used for progressive forms unresponsive to previous therapies. CLBCL LT forms are more aggressive and occur in older subjects. These lymphomas are best treated with age-adapted combinations of polychemotherapies and rituximab. Appropriate clinical trials are still needed to strengthen the levels of evidence of current recommendations.

Treatment of Cutaneous B-Cell Lymphoma, Leg Type, With Age-Adapted Combinations of Chemotherapies and Rituximab

Treatment of Cutaneous B-Cell Lymphoma, Leg Type, With Age-Adapted Combinations of Chemotherapies and Rituximab

Indolent primary cutaneous B-cell lymphoma: Experience using systemic rituximab

Optimal treatment of indolent primary cutaneous B-cell lymphoma (CBCL), marginal zone lymphoma, and follicle center lymphoma, presenting as multiple lesions, has yet to be established. Rituximab is a chimeric monoclonal IgG1 antibody directed against the CD20 antigen of B cells. Clinical efficacy of systemic rituximab in CBCL has yet to be established. We sought to assess the efficacy of systemic rituximab in the treatment of CBCL. This was a retrospective study of 15 patients with indolent CBCL treated with intravenous rituximab (375 mg/m(2)) as a single agent. Variable maintenance regimen was used in a subset of patients. Responses were categorized as complete response, partial response, stable disease, or progressive disease. The efficacy end points included were objective response rate, time to response, time to progression, and duration of response. Ten patients with follicle center lymphoma and 5 with marginal zone lymphoma were included. The objective response rate was 87% (60% complete response, 27% partial response). All patients with follicle center lymphoma had a response with 80% achieving complete response. Of the patients with marginal zone lymphoma, 3 had a response, one stable disease, and one progressive disease. Median follow-up was 36 months. Median time to response, duration of response, and time to progression was 30 days, 24 months, and 24 months, respectively. The study was limited by the small sample size and retrospective design. This study, although small, suggests that rituximab is a reasonable first-line treatment option for indolent CBCL with multiple lesions where local treatment is not effective or desirable.

Dilemmas associated with the surgical treatment of cutaneous B cell lymphomas

Cutaneous lymphomas belong to the group of non-Hodgkin lymphomas. However, in case of an in-time diagnose and adequate treatment the prognosis of the disease is fairly good. Nevertheless, a thorny path leads to the correct diagnosis as several dermatological diseases cause problems in differential diagnostics. The authors describe the case history of a 53-year-old woman patient, who had a dermatological check-up due to a dermatitis in the shoulder region. A conservative treatment was started because of a suspected mycosis. Following its inefficiency an operative excision was carried out. The postoperative biopsy verified cutaneous B-cell lymphoma. The cutaneous B-cell lymphomas are such forms of non-Hodgkin lymphomas, where the malignant proliferation appears primarily in the skin, and in 6 months after the diagnosis extracutaneous manifestation cannot be detected. Several cases can be found in the literature, which show long interval between the manifestation of the symptoms and the setting of the diagnosis. This calls the attention to the significance of difficulties in the differential diagnosis. During the treatment of cutaneous lymphomas the type, the cutaneous extension, and the extracutaneous manifestation of the disease must be defined. The therapeutic plan can be made up by analysing these findings. On the basis of findings in this case and in the literature, a surgical treatment--beyond determining the correct diagnosis--could be a therapeutic alternative in the treatment of cutaneous B-cell lymphomas.

Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases

Rituximab (MabThera); Roche, Basel, Switzerland; an anti-CD20 chimeric monoclonal antibody) has been shown to have significant activity in nodal B-cell lymphomas, with few associated adverse effects. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. Intravenous and subsequently intralesional administration of rituximab have also been reported to be effective and well tolerated in cutaneous B-cell lymphoma (CBCL). The comparative efficacy of intravenous vs. intralesional rituximab in CBCL is not known. To evaluate the objective response rate, relapse rate, time to progression, and tolerance in patients with CBCL treated with intravenous or intralesional rituximab. Eight patients with multiple primary CBCL (four follicle centre lymphoma and four marginal zone lymphoma) were treated with intralesional rituximab (six patients; 10-30 mg per lesion, three times weekly for one or two cycles at a 4-week interval) or intravenous rituximab (two patients; 375 mg m(-2) once weekly for four consecutive weeks). Complete clinical remission was obtained in all cases. The two patients treated intravenously did not relapse during a follow-up period of 18-24 months. Four of six patients treated intralesionally presented a relapse of new lesions at another site within a mean of 6 months after treatment. The injected lesions did not, however, recur. New lesions also responded to another cycle of intralesional rituximab. Tolerance to treatment was very good in both treatment groups. Rituximab therapy of CBCL appears to have a potential advantage in cases where lesions are localized in sites that are difficult to treat with radiotherapy or surgery and in which secondary scarring or alopecia is likely. Intralesional injections of rituximab allow the use of considerably smaller doses compared with intravenous treatment, with similar response rates and tolerance. However, within a 12-month follow-up period, relapse of CBCL with new lesions at distinct sites was frequently observed after intralesional treatment.

Cutaneous B-cell lymphoma responds to rituximab: A report of five cases and a review of the literature

Optimal treatment of cutaneous B-cell lymphoma (CBCL) is yet to be established. We treated five patients, each with either extensive lesions, severe comorbidities or who refused treatment with radiation therapy, with rituximab given as a single agent for four weekly intravenous infusions of 375 mg/m2. Maintenance therapy, if initiated, was given at 375 mg/m2 once every 2 – 3 months. Objective clinical responses occurred in all five patients. Three patients have ongoing complete clinical remissions with a median follow-up of 17, 19 and 39 months post achievement of complete remission. One patient died at age 87 years from a non-related cause after 5.5 years of complete remission. One patient received local radiotherapy to a solitary cutaneous site of large-cell lymphoma that developed after 3 years in remission from the low-grade CBCL; no recurrences of either grade CBCL have yet occurred. Treatment was well tolerated. Rituximab is safe and effective in treating of CBCL, either primary CBCL or low-grade lymphomas with relapses limited to the skin. Rituximab appears to present an attractive alternative when radiation therapy is contraindicated or unwanted. Additional collaborative studies are needed to assess the role of rituximab in various clinicopathologic presentations of CBCL.