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Research Letter |

Efficacy of Vinblastine in Primary Cutaneous Anaplastic Large Cell Lymphoma FREE

Pauline Laly, MD1; Saskia Ingen-Housz-Oro, MD2; Marie Beylot-Barry, MD, PhD3; Laurence Verneuil, MD, PhD4; Henri Adamski, MD5; Pauline Brice, MD6; Martine Bagot, MD, PhD1,7
[+] Author Affiliations
1Department of Dermatology, Assistance Publique–Hôpitaux de Paris, Saint-Louis Hospital, Paris, France
2Department of Dermatology, Assistance Publique–Hôpitaux de Paris, Henri Mondor Hospital, Créteil, France
3Department of Dermatology, Bordeaux University Hospital, Bordeaux, France
4Department of Dermatology, Caen University Hospital, Caen, France
5Department of Dermatology, Rennes University Hospital, Rennes, France
6Department of Haematology, Assistance Publique–Hôpitaux de Paris, Saint-Louis Hospital, Paris, France
7Department of Dermatology, Université Sorbonne, Paris, France
JAMA Dermatol. 2015;151(9):1030-1031. doi:10.1001/jamadermatol.2015.1357.
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Published online

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare primary cutaneous CD30+ T-cell lymphoproliferative disorder that affects patients at a median age of 60 years. The disease presents as localized or less frequently disseminated nodules, plaques, or ulcers that mostly affect limbs. Prognosis is favorable (5-year overall survival, >80%). According to the consensus recommendations,1 surgical excision or radiotherapy is recommended for localized lesions. For multifocal lesions, low-dose methotrexate is commonly used with a favorable response.2 Multiagent chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, is effective but because of adverse effects and a high rate of relapses is reserved for disseminated relapse and extracutaneous dissemination.1 Brentuximab vedotin has excellent effectiveness,3 but its use remains off label, expensive, and sometimes responsible for neuropathy and severe infectious complications. Consequently, therapeutic recommendations are lacking for patients with methotrexate failure, especially for older patients. We report a series of 7 patients who received vinblastine as single-agent chemotherapy for relapsing multifocal C-ALCL.

We retrospectively collected files of patients with C-ALCL (without lymph node invasion) who received vinblastine as monotherapy in the dermatology departments of the institution members of the Cutaneous Lymphoma French Study Group. Institutional review board approval and informed consent were not required because this is a retrospective study.

Seven patients (4 men) in their 30s to 90s (4 patients ≥70 years old) were included. The TNM stage4 was T1 in 1 case, T2 in 4 cases, and T3 in 2 cases. Lower limbs were involved in 6 cases. Median time from diagnosis was 5 years (range, 0.3-19 years). Six patients had previously received treatments with topical corticosteroids (n = 1), surgery (n = 1), radiotherapy (n = 4), methotrexate (n = 4), and/or multiagent chemotherapy (n = 3). One patient had contraindication to methotrexate (chronic renal insufficiency with anemia).

All patients received 6 mg/m2 of vinblastine twice a month, except for 1 patient, who received 4 mg/m2. All patients had partial (>75%) or complete remission after a median of 4 infusions (Figure). Four patients experienced hematologic adverse effects: 3 had neutropenia (lowest neutrophil count was 153/μL [to convert to ×109/L, multiply by 0.001], 2 patients received granulocyte-colony stimulating factor), and 2 patients had anemia (lowest hemoglobin value was 7.3 g/dL [to convert to grams per liter, multiply by 10], 1 patient underwent transfusion). There were no infectious complications or neuropathy.

Place holder to copy figure label and caption
Figure.
Pretreatment and Posttreatment Results of Vinblastine Treatment in Patient 7
Graphic Jump Location

Six patients experienced relapse after a median progression-free survival of 6 months (range, 3.5–28 months; median number of infusions, 10; range, 6-55) but relapse in 5 cases was limited to a slow worsening of previous lesions. When relapse occurred after discontinuation of treatment (n = 1) or after a longer interval between infusions (4 weeks, n = 1), rechallenge was effective. Furthermore, for the patient who began taking vinblastine at 4 mg/m2, increasing the dose to 6 mg/m2 was effective. However, in 3 patients, treatment was modified because of relapse (with the administration of brentuximab, radiotherapy, or autograft).

Considering the age of patients affected by C-ALCL and the good prognosis of the disease, therapy with a favorable benefit to risk ratio is needed. Despite little strong evidence, low-dose methotrexate seems to be a first-line therapy with a very good safety profile, especially for older patients.2 Brentuximab therapy was effective for CD30+ cutaneous lymphomas in a phase 2 study with an overall response rate of 70% and progression-free survival of 150 days3 and also seems promising in other types of cutaneous T-cell lymphomas in an allogenic stem cell transplantation plan.5 However, its use is limited by its cost and the risk of neuropathy and severe infectious complications.

We report, for the first time to our knowledge, the efficacy of vinblastine as monotherapy for C-ALCL. Vinblastine is a vinca alkaloid commonly used in dermatology as a single agent in the treatment of Kaposi sarcoma with good tolerance, even in older patients. Vinblastine is successfully used as monotherapy for pediatric systemic ALCL6 but, to our knowledge, has never been reported for primary cutaneous lymphomas.

In our series, all patients had quick good-quality remission with a median progression-free survival of 6 months. The rapidity of the response supports the role of vinblastine instead of spontaneous regression in these patients with multifocal lesions and a long-term history of refractory disease. In our series, no patient had to discontinue use of the drug because of infection or severe toxic effects.

Vinblastine should be studied in larger series to confirm its effectiveness and tolerance in disseminated or refractory C-ALCL. Its place as second-line treatment could be considered with failure of methotrexate and perhaps as first-line treatment in the case of contraindication to methotrexate, especially in older adults.

Accepted for Publication: April 9, 2015.

Corresponding Author: Saskia Ingen-Housz-Oro, MD, Department of Dermatology, Henri Mondor Hospital, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France (saskia.oro@hmn.aphp.fr).

Published Online: June 24, 2015. doi:10.1001/jamadermatol.2015.1357.

Author Contributions: Drs Laly and Ingen-Housz-Oro had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Ingen-Housz-Oro, Beylot-Barry, Brice, Bagot.

Acquisition, analysis, or interpretation of data: Laly, Ingen-Housz-Oro, Beylot-Barry, Verneuil, Adamski, Bagot.

Drafting of the manuscript: Laly, Ingen-Housz-Oro, Verneuil.

Critical revision of the manuscript for important intellectual content: Laly, Beylot-Barry, Adamski, Brice, Bagot.

Administrative, technical, or material support: Beylot-Barry.

Study supervision: Beylot-Barry, Adamski, Brice, Bagot.

Conflict of Interest Disclosures: None reported.

Additional Contributions: Amir Mirkamali, MD ( Assistance Publique–Hôpitaux de Paris, Henri Mondor Hospital, Créteil, France), Caroline Brugières, MD (Caen University Hospital, Caen, France), Monica Dinulescu, MD (Rennes University Hospital, Rennes, France), and Anne Pham-Ledard, MD, PhD (Bordeaux University Hospital, Bordeaux, France), participated in the management of the patients and did not receive any compensation for their role.

Additional Information: Drs Ingen-Housz-Oro, Beylot-Barry, Verneuil, Adamski, and Bagot are members of the Cutaneous Lymphoma French Study Group.

Kempf  W, Pfaltz  K, Vermeer  MH,  et al.  EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Blood. 2011;118(15):4024-4035.
PubMed   |  Link to Article
Fujita  H, Nagatani  T, Miyazawa  M,  et al.  Primary cutaneous anaplastic large cell lymphoma successfully treated with low-dose oral methotrexate. Eur J Dermatol. 2008;18(3):360-361.
PubMed
Duvic  M, Reddy  SA, Pinter-Brown  L,  et al.  A phase II study of SGN-30 in cutaneous anaplastic large cell lymphoma and related lymphoproliferative disorders. Clin Cancer Res. 2009;15(19):6217-6224.
PubMed   |  Link to Article
Kim  YH, Willemze  R, Pimpinelli  N,  et al; ISCL and the EORTC.  TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(2):479-484.
PubMed   |  Link to Article
Mehra  T, Ikenberg  K, Moos  RM,  et al.  Brentuximab as a treatment for CD30+ mycosis fungoides and Sézary syndrome. JAMA Dermatol. 2015;151(1):73-77.
PubMed   |  Link to Article
Brugières  L, Pacquement  H, Le Deley  MC,  et al.  Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma: a report from the French Society of Pediatric Oncology. J Clin Oncol. 2009;27(30):5056-5061.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Pretreatment and Posttreatment Results of Vinblastine Treatment in Patient 7
Graphic Jump Location

Tables

References

Kempf  W, Pfaltz  K, Vermeer  MH,  et al.  EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Blood. 2011;118(15):4024-4035.
PubMed   |  Link to Article
Fujita  H, Nagatani  T, Miyazawa  M,  et al.  Primary cutaneous anaplastic large cell lymphoma successfully treated with low-dose oral methotrexate. Eur J Dermatol. 2008;18(3):360-361.
PubMed
Duvic  M, Reddy  SA, Pinter-Brown  L,  et al.  A phase II study of SGN-30 in cutaneous anaplastic large cell lymphoma and related lymphoproliferative disorders. Clin Cancer Res. 2009;15(19):6217-6224.
PubMed   |  Link to Article
Kim  YH, Willemze  R, Pimpinelli  N,  et al; ISCL and the EORTC.  TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(2):479-484.
PubMed   |  Link to Article
Mehra  T, Ikenberg  K, Moos  RM,  et al.  Brentuximab as a treatment for CD30+ mycosis fungoides and Sézary syndrome. JAMA Dermatol. 2015;151(1):73-77.
PubMed   |  Link to Article
Brugières  L, Pacquement  H, Le Deley  MC,  et al.  Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma: a report from the French Society of Pediatric Oncology. J Clin Oncol. 2009;27(30):5056-5061.
PubMed   |  Link to Article

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