When and which aggressive treatment ? CHEMOTHERAPY IN CTCL N. Pimpinelli Dept. Dermatological Sciences University of Florence Med. School Florence, Italy

CHEMOTHERAPY in CTCL: WHEN CHEMOTHERAPY in CTCL: WHEN ? advanced MF (stage IIB-IV) SS (high tumor load) CD30+ ALC (disseminated lesions) SPLTL (with progressive lesions) EXTRANODAL NK/T-CELL LY, NASAL TYPE PTL-U (with few exceptions) any refractory CTCL

CHEMOTHERAPY IN ADVANCED MF: monoCT vs. poliCT 2-CDA (Kuzel et al. 1996; Trautinger et al. 1999 – 51-55% OR) Pentostatin (Kurzrock et al. 1999 – 71% OR) Gemcitabine (Zinzani et al. 1998, 2000; Marchi et al. 2005; Duvic et al. 2006 – 68-75% OR) Peg-Doxo (Wollina et al. 2003; Pulini et al. submitted – 86-88% OR) PFS 10-15 mos. PoliCT (Bunn et al. 1884; Fierro et al. 1997; Apisarnthanarax et al. 2002; Cantonetti et al. 2005) – 57-90% OR) PFS 5-11 mos.

poliCT results in stage IIB/IVB better than in III/IVA CHEMOTHERAPY IN ADVANCED MF: monoCT vs. poliCT monoCT > poliCT (much less side effects and immunosuppression) poliCT if high tumor load and generally in stage IV pts. results in stage IIB/IVB better than in III/IVA

Patients with Sézary Syndrome (SS) with a low tumor load, oral chemotherapy (chlorambucil plus prednisone) is a possible treatment alternative to ECP, denileukin diftitox, and IFN. Patients with high tumor load and patients refractory to/relapsing after a first line treatment should be treated with chemotherapy, (monoCT vs. poliCT ? Consider risk of immunosuppression and quality of life). Consider possible combination treatments, either concurrent or sequential (bexarotene, alemtuzumab)

WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005 Patients with primary cutaneous CD30+ ALC lymhoma with progressing, multiple lesions in non-contiguous sites (and those with regional nodal involvement) can benefit of polychemotherapy (CHOP-like regimens), with a considerable cure rate. WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005

WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005 In patients with subcutaneous, panniculitis-like T-cell lymphoma, chemotherapy (monoCT vs. poliCT) is recommended for patients with multiple and/or progressing lesions. WWhittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005

Whittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005 PPolychemotherapy (CHOP-like regimens) is recommended as palliative treatment in extranodal NK/T-cell ly. nasal type and primary cutaneous peripheral T-cell lymphoma-U, due to their by far generally aggressive course. Hvery good ORR (up to 100% in front line) with monoCT (Gemcitabine – Zinzani et al. 2000, Marchi et al. 2005; Peg-Doxo – Pulini et al, submitted) PPatients with isolated or localized lesions and CD4+ small/medium pleomorphic T-cell histology should be treated non-aggressively at presentation (radiotherapy, surgical excision in unilesional cases). Whittaker et al, 2003; Dummer et al, 2003; Willemze et al, 2005

What patients should be considered for autologous or allogeneic stem cell transplantation ?

problems and future directions Chemotherapy in CTCL: problems and future directions improving response: optimization of combination therapy improving progression-free survival: sequential consolidation with non-cytotoxic agents (oral bexarotene, low-dose alemtuzumab, IFN ?) improving quality of life: careful balance of pros and cons

THANK YOU ! Pimpi & co. S. Rupoli (Ancona) M.G. Bernengo (Torino) R. Alterini (Firenze) M. Cantonetti (Roma) P.L. Zinzani (Bologna)