Intralesional rituximab in the treatment of indolent primary cutaneous B‐cell lymphoma

Dear Editor, Primary cutaneous B‐cell lymphomas (PCBCLs) are a heterogeneous group of extranodal lymphomas.1 Primary cutaneous marginal zone lymphoma (MZL) and follicle centre lymphoma (FCL), the most prevalent PCBCLs, are typically indolent. Various treatments are available for MZL and FCL, including intralesional (IL) rituximab, a chimeric monoclonal IgG antibody against CD20, a major B‐cell marker.2 However, there remain few reports of IL rituximab in PCBCL, and its ideal administration schedule remains undefined.3–5 In this study, we evaluated the efficacy, safety and tolerability of IL rituximab in PCBCL, including the use of weekly injections – a schedule not previously described. We reviewed the charts of adult patients diagnosed with MZL/FCL and treated with IL rituximab at McGill University’s Jewish General Hospital between January 2014 and December 2018. Rituximab was prepared daily as a 3‐mL aliquot of the stock 10 mg mL–1 solution. It was injected intralesionally until the lesion blanched, for a maximum of 30 mg per session, without premedication. In the case of relapse, salvage therapy was determined accounting for patient preference of repeat IL rituximab vs. radiotherapy. We noted: age, sex, PCBCL type, tumour–nodes–metastasis stage,2 previous treatments, number and location of lesions, rituximab dose, frequency and number of injections, treatment response, toxicity, and patient satisfaction. Treatment efficacy was evaluated by assessing clinical response according to the standardized cutaneous lymphoma criteria.6 Response was used to compute objective response rates, i.e. the proportion of patients with either complete or partial response. This review was approved by the institutional research ethics committee. Twelve patients were included in this series (Table 1). None had extracutaneous involvement. The median patient age was 49 years (range 19–80). Patients had local/regional disease on scalp/face, trunk, and/or extremities. Median duration of follow‐up was 3·2 years (range 1·9–6·1). The median number of prior treatments was one (range 0–2). Radiotherapy was the most common prior treatment (n = 7). Only one participant (patient 4) had prior radiotherapy administered to the same lesion treated with IL rituximab. Characteristics of study cohort and rituximab injections F, female; M, male; MZL, marginal zone lymphoma; FCL, follicle centre lymphoma; RT, radiotherapy; TCS, topical corticosteroids; ILCS, intralesional corticosteroids; UE, upper extremity; LE, lower extremity; CR, complete response; PR, partial response; SD, stable disease; NR, no relapse. aGrade 1 (mild).7 Characteristics of study cohort and rituximab injections F, female; M, male; MZL, marginal zone lymphoma; FCL, follicle centre lymphoma; RT, radiotherapy; TCS, topical corticosteroids; ILCS, intralesional corticosteroids; UE, upper extremity; LE, lower extremity; CR, complete response; PR, partial response; SD, stable disease; NR, no relapse. aGrade 1 (mild).7 The overall response rate was 92% (11 of 12). Complete response (CR) was observed in 83% (10 of 12) of the patients treated with IL rituximab, while partial response and stable disease were each seen in one patient. Median time to CR was 4·5 weeks (range 3–8), with a median of six injections (range 3–10) and median cumulative dose of 84 mg (range 40–280). For all patients, treatment was stopped when they achieved CR, or at such time (after 12 injections) both patient and physician agreed that response had plateaued. The median disease‐free interval was 85·5 weeks (range 16–313). Overall, 75% (nine of 12) of the patients received dosing once weekly, while 25% (three of 12) received three‐times‐weekly injections. The sample size did not allow useful statistical comparison of the response rates for the two schedules or subgroup analysis for predictors of response. IL rituximab was safe and well tolerated. Adverse events reports were mild (grade 1)7 and were more common in the once‐weekly group (six of nine participants vs. none of three). Ninety‐two per cent of patients (11 of 12) expressed overall treatment satisfaction. Previous studies support the use of IL rituximab, most commonly with three injections per week for a varying number of weeks per month.2–5 In the largest study to date, the majority of patients achieved CR with frequent relapses and median disease‐free interval in the order of years.3 Our results reflect a similar tendency. To our knowledge, once‐weekly IL rituximab injections have not been reported previously in PCBCL. Both the once‐ and three‐times‐weekly treatment groups had favourable responses similar to those previously reported in the literature and were comparable with respect to safety. Once‐weekly injections are more convenient for both patient and physician, and cheaper for the healthcare system. Radiotherapy may lead to slightly greater local control;8 however, the dominant mode of failure will be in the form of new skin lesions. In these indolent processes, toxicity (including cosmesis) is an important consideration, and salvage treatment will often be effective. In conclusion, treatment with IL rituximab, including weekly dosing, demonstrated good safety and tolerability in PCBCL. Treated lesions all responded to IL rituximab, making it a useful alternative for lesions less suitable to radiotherapy or excision. Further research regarding use of IL rituximab in PCBCL, particularly on cosmesis, duration of action and dose schedule, will be helpful to clinicians. Anissa Chirico: Conceptualization (supporting); Data curation (lead); Formal analysis (equal); Methodology (supporting); Project administration (equal); Writing‐original draft (lead); Writing‐review & editing (equal). Meagan‐Helen Henderson Berg: Conceptualization (equal); Data curation (supporting); Formal analysis (equal); Methodology (equal); Project administration (equal); Writing‐original draft (supporting); Writing‐review & editing (lead). Kevin Pehr: Conceptualization (lead); Formal analysis (supporting); Methodology (equal); Project administration (equal); Resources (equal); Supervision (lead); Writing‐review & editing (supporting). David Roberge: Supervision (supporting). Funding sources: none. Conflicts of interest: The authors declare they have no conflicts of interest.

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