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Original Investigation |

Improvement of Survival in Patients With Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, in France

Florent Grange, MD, PhD1; Pascal Joly, MD, PhD2; Coralie Barbe, MD3; Martine Bagot, MD, PhD4; Stéphane Dalle, MD, PhD5; Saskia Ingen-Housz-Oro, MD6; Eve Maubec, MD, PhD7; Michel D’Incan, MD, PhD8; Caroline Ram-Wolff, MD4; Sophie Dalac, MD9; Isabelle Templier, MD10; Eric Esteve, MD11; Gaëlle Quereux, MD, PhD12; Laurent Machet, MD, PhD13; Marion Leduc, MSc14; Olivier Dereure, MD, PhD15; Liliane Laroche, MD, PhD16; Philippe Saiag, MD, PhD17; Béatrice Vergier, MD, PhD18; Marie Beylot-Barry, MD, PhD19
[+] Author Affiliations
1Department of Dermatology, Hôpital Robert Debré, Reims, France
2Department of Dermatology, Hôpital Charles Nicolle, Rouen, France
3Unité d’Aide Méthodologique, Hôpital Robert Debré, Reims, France
4Department of Dermatology, Hôpital Saint-Louis, Paris, France
5Department of Dermatology, Hôpital de l’Hôtel-Dieu, Lyon, France
6Department of Dermatology, Hôpital Henri-Mondor, Créteil, France
7Department of Dermatology, Hôpital Bichat, Paris, France
8Department of Dermatology, Hôtel-Dieu, Clermont-Ferrand, France
9Department of Dermatology, Hôpital du Bocage, Dijon, France
10Department of Dermatology, Hôpital Michallon, Grenoble, France
11Department of Dermatology, Hôpital Porte Madeleine, Orléans, France
12Department of Dermatology, Hôpital de l’Hôtel-Dieu, Nantes, France
13Department of Dermatology, Hôpital Trousseau, Tours, France
14Department of Clinical Research, Hôpital Maison Blanche, Reims, France
15Department of Dermatology, Hôpital Saint-Eloi, Montpellier, France
16Department of Dermatology, Hôpital Avicenne, Bobigny, France
17Department of Dermatology, Hôpital Ambroise Paré, Boulogne, France
18Department of Pathology, Hôpital du Haut Lévêque, Pessac, France
19Department of Dermatology, Hôpital du Haut Lévêque, Pessac, France
JAMA Dermatol. 2014;150(5):535-541. doi:10.1001/jamadermatol.2013.7452.
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Importance  Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), occurs in elderly patients and has been considered as a lymphoma with a poor prognosis, with estimated 5-year specific survival rates of approximately 50%. The hypothesis of an improvement in prognosis over time has not been studied.

Objectives  To evaluate this hypothesis in a large series of patients and investigate factors associated with prognosis as well as improvement in the prognosis.

Design, Setting, and Participants  A retrospective multicenter study was conducted including dermatology departments belonging to the French Study Group on Cutaneous Lymphoma. Participants were 115 patients with PCDLBCL-LT diagnosed between 1988 and 2003 (period 1) or between 2004 and 2010 (period 2).

Main Outcomes and Measures  Age, sex, period of diagnosis, number of skin lesions, tumor stage, tumor location (leg vs nonleg), lactate dehydrogenase level, type of therapy (with or without a combination of rituximab and polychemotherapy [PCT]), and outcome were recorded. Baseline characteristics and outcome were compared according to period of diagnosis and type of therapy. Prognosis factors were identified by univariate and multivariate survival analyses.

Results  The mean age of the patients was 76.9 years, and 47% of the patients were older than 80 years. The 3- and 5-year specific survival rates improved between period 1 and period 2, from 55% to 74% and from 46% to 66%, respectively (P = .01). Patients had similar baseline characteristics during both periods, but rituximab-PCT regimens were administered to 88.5% of the patients in period 2 vs 16.7% in period 1 (P < .001). The 3- and 5-year specific survival rates were 80% and 74%, respectively, in patients who received a rituximab-PCT regimen compared with 48% and 38% in those who received less-intensive therapies. No significant difference was observed between both groups in age and baseline prognostic factors. In multivariate analysis, treatment without rituximab-PCT was the only adverse prognostic factor (odds ratio, 4.6 [95% CI, 2.4-9.1]; P < .001), whereas the number of skin lesions (P = .06) and location on the leg (P = .07) had only borderline significance.

Conclusions and Relevance  A major improvement in the survival of patients with PCDLBCL-LT has occurred over time in France, mainly as a result of the use of intensive rituximab-PCT regimens in most patients, including very elderly ones. Until further prospective clinical trials are conducted, such regimens should be considered as the standard of care in these patients.

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Figure 1.
Specific Survival of 115 Patients With a Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, According to the Period of Diagnosis

Period 1 included 54 patients; period 2 included 61 patients. The difference in survival was significant (P = .01).

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Figure 2.
Specific Survival of 115 Patients With a Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, According to Type of Treatment

A, Survival of patients according to the most intensive therapy received. The therapies consisted of a combination of rituximab and polychemotherapy (PCT) with anthracycline, rituximab-PCT without anthracycline, PCT with anthracycline (without rituximab), PCT only (without anthracycline and/or rituximab), and less-intensive therapies only (including single-drug chemotherapy and radiotherapy). The global difference between the curves was significant (P = .002). B, Sixty-three patients received treatment at any time with rituximab-PCT; 52 patients only received other treatments (including PCT without rituximab). The difference between rituximab-PCT regimens and other treatments was significant (P < .001).

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