1. Evaluation of treatment results in multifocal primary cutaneous anaplastic large cell lymphoma: Report of the Dutch Cutaneous Lymphoma Group
Melchers RC1, Willemze R1, Bekkenk MW2, de Haas ERM3, Horvath B4, van Rossum MM5, Sanders CJG6, Veraart JCJM7, Vermeer MH1, Quint KD1.
1 Department of Dermatology, Leiden University Medical Center, The Netherlands.
2 Department of Dermatology, Academic Medical Center and Vrije University Medical Center, Amsterdam, The Netherlands.
3 Department of Dermatology, Erasmus Medical Center, Rotterdam, The Netherlands.
4 Department of Dermatology, University Medical Center of Groningen, The Netherlands.
5 Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.
6 Department of Dermatology, University Medical Center Utrecht, The Netherlands.
7 Department of Dermatology, Maastricht University Medical Center, The Netherlands.
British Journal of Dermatology. DOI: /bjd.16501

2. Rutger Melchers, Lead author

3. Introduction What’s already known?
There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C-ALCL).
New targeted therapies are evaluated without knowledge of the efficacy of conventional therapies.
Few published reports about treatment of multifocal C-ALCL

4. Objective
To assess the efficacy of conventional treatment strategies for patients with multifocal C-ALCL, and to define which patients may require novel targeted therapies.

5. 283 28 24 Methods Design: Multicenter study
C-ALCL patients in the Dutch registry of cutaneous lymphomas between
Multifocal C-ALCL patients
Final study group after exclusion of: ALK+ (n=1), insufficient follow-up (n=1), underlying immunodeficiency (n=1) and death before initial therapy (n=1)

6. Methods
Treatment was evaluated in patients initially presenting (n=24) and relapsing with multifocal C-ALCL (n=17; 23 relapses).
Endpoints: Complete response rate (CR) and overall response rate (ORR), (extracutaneous)relapse rate, 5-year disease specific (DSS) and overall survival (OS)
Distinction was made between cases with 2-5 (n=36) and cases with >5 lesions (n=11).

7. Extracutaneous relapse
Results
Patients initially presenting (n=24) with multifocal C-ALCL
19 male, 5 female
Median age 56 (range, 25-88)
2-5 lesions (n=15) vs >5 lesions (n=9)
Treatment .
Therapy No CR
Relapse only skin
Extracutaneous relapse
Total relapse
CHOP 5
5/5 (100%)
2/5
3/5
MTX 4
1/4 (25%)
1/4
2/4
3/4 (75%)
RT (+ excision) 7
7/7 (100%)
5/7
0/7
5/7 (71%)
Spontaneous remission
4/4 (100%)
0/4

8. Results (follow-up)
16/24 patients (67%) developed a relapse (8 (33%) extracutaneous)
Median time to relapse: 12.5 months (range, 4-20 months)
5-year DSS: 78%, 5-year OS: 66%
Compared to patients presenting with 2-5 skin lesions, patients presenting with >5 lesions had a higher chance of developing extracutaneous relapse (56% vs 20%) and more often died of lymphoma (44% vs 7%).

9. Cumulative results of treatment
47 clinical presentations of multifocal C-ALCL
Therapy No
>5 lesions CR
ORR
CHOP 9
3/9 (33%)
7/9 (78%)
9/9 (100%)
MTX 7
4/7 (57%)
3/7 (43%) RT 21
0/21 (0%)
21/21 (100%)
Spontaneous remission 4
2/4 (50%)
4/4 (100%)
Other 6
2/6 (33%)
4/6 (66%)
6/6 (100%)
Total 47
11/47 (23%)
39/47 (83%)
44/47 (94%)
Most patients with 2-5 lesions were treated with RT
Most patients with >5 lesions were treated with CHOP or MTX

10. Conclusion (I)
Multifocal C-ALCL is rare  10% of all C-ALCL  3% had >5 lesions
High relapse rate (67%); 33% developed extracutaneous disease
No role for CHOP

11. Conclusion (II)
Patients with ≤5 lesions should be treated with low-dose RT (2x4 Gy).
Maintenance low-dose MTX (20 mg/week) is a suitable option in patients with >5 lesions.
In patients showing signs of spontaneous remission, an expectant policy should be considered.
Targeted therapies may be considered in rare patients refractory to MTX or patients developing extracutaneous disease.

12. Solitary/localized (90%)
Treatment flow-chart
C-ALCL
Solitary/localized (90%) RT
Multifocal (10%)
≤5 lesions (7%)
>5 lesions (3%)
MTX
Targeted Therapies

13. What does this study add?
This study evaluated the efficacy of conventional therapies for multifocal C-ALCL.
Radiotherapy and low-dose methotrexate are suitable options in patients with ≤5 and >5 lesions, respectively.
Targeted therapies may be considered in rare patients refractory to methotrexate or developing extracutaneous disease.

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