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Programmed death 1 expression in mycosis fungoides and Sézary syndrome
LYMPHOMA, CUTANEOUS/MYCOSIS FUNGOIDES P2700 Defining early mycosis fungoides: Validation of a diagnostic algorithm proposed by the International Society for Cutaneous Lymphomas Travis Vandergriff, MD, University of Texas Southwestern Medical Center, Dallas, TX, United States; Amit Pandya, MD, University of Texas Southwestern Medical Center, Dallas, TX, United States; Joseph Susa, DO, University of Texas Southwestern Medical Center, Dallas, TX, United States; Kaveh Nezafati, MD, University of Texas Southwestern Medical Center, Dallas, TX, United States; Laszlo Karai, MD, PhD, University of Texas Southwestern Medical Center, Dallas, TX, United States Background: Mycosis fungoides (MF) is the most common subtype of cutaneous Tcell lymphoma and is often difficult to diagnose in its early stages. In order to facilitate the early diagnosis of MF, an algorithm has been proposed by the International Society for Cutaneous Lymphomas (ISCL) whereby clinical and histopathologic characteristics as well as immunohistochemistry and T-cell receptor gene rearrangement studies may be applied to suspected cases of MF. The algorithm proposes a scoring system in which MF is diagnosed when a total of 4 points is achieved. The diagnostic utility of this algorithm has not yet been tested or validated. Objective: We sought to determine the validity of the proposed algorithm via an investigator-blinded, retrospective case-control study including patients with known MF and patients with clinicopathologic mimics of MF, such as drug eruptions, psoriasis, and other dermatoses who were referred to rule out MF. Methods: Thirty-five cases were randomly selected from the database of the cutaneous lymphoma clinic at the University of Texas Southwestern Medical Center. Only cases with an uncertain diagnosis at the time of their referral and at least 6 months of follow-up were included in the study. The cohort ultimately included patients with MF and patients with clinicopathologic mimics. Clinical features of each patient were gleaned from a review of their charts. The skin biopsies obtained at the time of their initial referral were evaluated in an investigator-blinded fashion by two dermatopathologists. Each case was assigned a composite score based on the parameters in the proposed algorithm. Results: The proposed algorithm appropriately distinguishes cases of MF from its clinical and histopathologic mimics. Nearly all of the cases of MF achieved a composite score of 4 or more points. Most cases that were not MF achieved three or fewer points. This difference was determined to be statistically significant. Limitations: This was a retrospective study.
P2702 Hypopigmented mycosis fungoides treated with narrowband UVB: A 10-year retrospective study Silada Kanokrungsee, MD, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Vasanop Vachiramon, MD, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Background: Hypopigmented mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma. Phototherapy including psoralen plus ultraviolet A (PUVA), broadband UVB, and narrowband UVB (NB-UVB) have been widely used for the treatment of MF. However, no study has been reported the efficacy of NB-UVB for hypopigmented MF. Objectives: The purpose of this study was to evaluate the effectiveness of NB-UVB for the treatment of hypopigmented MF. Methods: We performed a retrospective review of the hospital databases and records of hypopigmented MF patients who were treated with NB-UVB between 2000 and 2009. Results: Thirteen patients were treated with NB-UVB (9 men, 4 women). Average age of onset is 26.5 years (range, 6-75 years). Five patients had stage 1A and eight had stage 1B. The most common site of involvement is upper extremity (84.6%). At the eleventh session, all patients had clinical improvement more than 50%. Complete clinical response was achieved after a median 36 treatment sessions (range, 14-136). After discontinuing the treatment, eight of 13 patients (61.5%) had relapse. Median time to relapse is 5.5 months (range, 2-12 months). The age of disease onset, stage of the disease, and number of treatment sessions are not statistically significant predictors of relapse. Conclusion: NB-UVB is an effective treatment for hypopigmented MF. However, the relapse rate is high. Unfortunately, no clinical feature can predict the relapse of the disease. Commercial support: None identified.
Conclusion: The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. Establishing the validity of the algorithm provides dermatologists and oncologists with a tool that can be used both in clinical practice and to improve the quality of future studies of patients with MF. Commercial support: None identified.
P2703 Low dose electron beam radiation to localized symptomatic CTCL lesions further improves clinical responses to romidepsin Oleg Akilov, MD, PhD, University of Pittsburgh, Pittsburgh, PA, United States; Cliona Grant, MD, Center for Cancer Research NIH, Bethesda, MD, United States; Larisa Geskin, MD, University of Pittsburgh, Pittsburgh, PA, United States; Richard Piekarz, MD, Center for Cancer Research NIH, Bethesda, MD, United States; Susan Bates, MD, Center for Cancer Research NIH, Bethesda, MD, United States
Programmed death 1 expression in mycosis fungoides and S ezary syndrome David Wada, MD, Mayo Clinic, Rochester, MN, United States; Nneka Comfere, MD, Mayo Clinic, Rochester, MN, United States; Susan Harrington, MS, Mayo Clinic, Rochester, MN, United States; Wilcox Ryan, MD, PhD, Mayo Clinic, Rochester, MN, United States Expression of PD-1 (receptor programmed death-1, CD279) in some peripheral Tcell lymphomas has recently been shown. Because antibody-based therapies have improved outcomes in non-Hodgkin lymphoma, and antibodies targeting PD-1 are in clinical development, PD-1 expression in T-cell lymphomas may be of therapeutic interest. There are no studies specifically addressing the frequency of PD-1 expression in MF or SS to date. We characterized PD-1 expression in mycosis fungoides (MF) and Sezary syndrome (SS) by immunohistochemistry (IHC) on lesional skin biopsies and by flow cytometry on peripheral blood. Fifteen out of 30 cases of mycosis fungoides and eight of 11 cases of SS were positive for PD-1 by (IHC). Circulating tumor cells from 5 of the IHC-positive cases of SS were tested by flow cytometry, all of which were positive for surface PD-1 expression. This data indicates that a substantial proportion of MF and SS are PD-1 positive, and warrants further study on PD-1 as a potential therapeutic target.
Romidepsin is a second of its class of histone deacetylase inhibitors that was recently FDA-approved for therapy of cutaneous T-cell lymphoma (CTCL) based on data from two clinical trials (pivotal and NCI trials) demonstrating 34% to 35% response rates in total of 167 patients as a single chemotherapeutic agent. In phase II of the clinical trial spearheaded by NCI, the endpoints for the response to the drug were assessed in all compartments including skin, lymph nodes, viscera, and blood. Responses in the skin were calculated based on five selected target lesions; the SWAT score was not a part of the response assessment. This trial design allowed for limited localized radiation to symptomatic nontarget lesions, which were not included in the final calculation of the response. Patients who received localized radiation were not considered complete responders at any point. We present five patients who received localized electron beam radiation to symptomatic non-target lesions during romidepsin therapy. All patients with advanced mycosis fungoides (2 had IIB, and 3 had IVA2). On average, 2.4 LEBT were administered during therapy with romidepsin. Three patients received LEBT during cycles 6 to 7, three patients received LEBT during cycles 10 to 12, and one patient received LEBT during cycles 43 to 44. None of these patients experienced additional or unexpected toxicity. Four out of five patients demonstrated durable responses, which allow remaining them on clinical trial protocol. There is a significant preclinical data suggesting that HDAC inhibitors, especially romidepsin, may show synergy when used with electron beam or other therapeutic modality such as UV irradiation. Combinations of HDAC inhibitors with LEBT allow significantly decrease the dose of ionizing radiation maintaining high biologic effect. Our initial positive experience using concurrent electron beam and romidepsin therapy warrants further investigation to evaluate this combination in clinical trial.
Commercial support: None identified.
Commercial support: None identified.
P2701
AB114
J AM ACAD DERMATOL
FEBRUARY 2011
P2702 Hypopigmented mycosis fungoides treated with narrowband UVB: A 10-year retrospective study Silada Kanokrungsee, MD, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Vasanop Vachiramon, MD, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Background: Hypopigmented mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma. Phototherapy including psoralen plus ultraviolet A (PUVA), broadband UVB, and narrowband UVB (NB-UVB) have been widely used for the treatment of MF. However, no study has been reported the efficacy of NB-UVB for hypopigmented MF. Objectives: The purpose of this study was to evaluate the effectiveness of NB-UVB for the treatment of hypopigmented MF. Methods: We performed a retrospective review of the hospital databases and records of hypopigmented MF patients who were treated with NB-UVB between 2000 and 2009. Results: Thirteen patients were treated with NB-UVB (9 men, 4 women). Average age of onset is 26.5 years (range, 6-75 years). Five patients had stage 1A and eight had stage 1B. The most common site of involvement is upper extremity (84.6%). At the eleventh session, all patients had clinical improvement more than 50%. Complete clinical response was achieved after a median 36 treatment sessions (range, 14-136). After discontinuing the treatment, eight of 13 patients (61.5%) had relapse. Median time to relapse is 5.5 months (range, 2-12 months). The age of disease onset, stage of the disease, and number of treatment sessions are not statistically significant predictors of relapse. Conclusion: NB-UVB is an effective treatment for hypopigmented MF. However, the relapse rate is high. Unfortunately, no clinical feature can predict the relapse of the disease. Commercial support: None identified.
Conclusion: The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. Establishing the validity of the algorithm provides dermatologists and oncologists with a tool that can be used both in clinical practice and to improve the quality of future studies of patients with MF. Commercial support: None identified.
P2703 Low dose electron beam radiation to localized symptomatic CTCL lesions further improves clinical responses to romidepsin Oleg Akilov, MD, PhD, University of Pittsburgh, Pittsburgh, PA, United States; Cliona Grant, MD, Center for Cancer Research NIH, Bethesda, MD, United States; Larisa Geskin, MD, University of Pittsburgh, Pittsburgh, PA, United States; Richard Piekarz, MD, Center for Cancer Research NIH, Bethesda, MD, United States; Susan Bates, MD, Center for Cancer Research NIH, Bethesda, MD, United States
Programmed death 1 expression in mycosis fungoides and S ezary syndrome David Wada, MD, Mayo Clinic, Rochester, MN, United States; Nneka Comfere, MD, Mayo Clinic, Rochester, MN, United States; Susan Harrington, MS, Mayo Clinic, Rochester, MN, United States; Wilcox Ryan, MD, PhD, Mayo Clinic, Rochester, MN, United States Expression of PD-1 (receptor programmed death-1, CD279) in some peripheral Tcell lymphomas has recently been shown. Because antibody-based therapies have improved outcomes in non-Hodgkin lymphoma, and antibodies targeting PD-1 are in clinical development, PD-1 expression in T-cell lymphomas may be of therapeutic interest. There are no studies specifically addressing the frequency of PD-1 expression in MF or SS to date. We characterized PD-1 expression in mycosis fungoides (MF) and Sezary syndrome (SS) by immunohistochemistry (IHC) on lesional skin biopsies and by flow cytometry on peripheral blood. Fifteen out of 30 cases of mycosis fungoides and eight of 11 cases of SS were positive for PD-1 by (IHC). Circulating tumor cells from 5 of the IHC-positive cases of SS were tested by flow cytometry, all of which were positive for surface PD-1 expression. This data indicates that a substantial proportion of MF and SS are PD-1 positive, and warrants further study on PD-1 as a potential therapeutic target.
Romidepsin is a second of its class of histone deacetylase inhibitors that was recently FDA-approved for therapy of cutaneous T-cell lymphoma (CTCL) based on data from two clinical trials (pivotal and NCI trials) demonstrating 34% to 35% response rates in total of 167 patients as a single chemotherapeutic agent. In phase II of the clinical trial spearheaded by NCI, the endpoints for the response to the drug were assessed in all compartments including skin, lymph nodes, viscera, and blood. Responses in the skin were calculated based on five selected target lesions; the SWAT score was not a part of the response assessment. This trial design allowed for limited localized radiation to symptomatic nontarget lesions, which were not included in the final calculation of the response. Patients who received localized radiation were not considered complete responders at any point. We present five patients who received localized electron beam radiation to symptomatic non-target lesions during romidepsin therapy. All patients with advanced mycosis fungoides (2 had IIB, and 3 had IVA2). On average, 2.4 LEBT were administered during therapy with romidepsin. Three patients received LEBT during cycles 6 to 7, three patients received LEBT during cycles 10 to 12, and one patient received LEBT during cycles 43 to 44. None of these patients experienced additional or unexpected toxicity. Four out of five patients demonstrated durable responses, which allow remaining them on clinical trial protocol. There is a significant preclinical data suggesting that HDAC inhibitors, especially romidepsin, may show synergy when used with electron beam or other therapeutic modality such as UV irradiation. Combinations of HDAC inhibitors with LEBT allow significantly decrease the dose of ionizing radiation maintaining high biologic effect. Our initial positive experience using concurrent electron beam and romidepsin therapy warrants further investigation to evaluate this combination in clinical trial.
Commercial support: None identified.
Commercial support: None identified.
P2701
AB114
J AM ACAD DERMATOL
FEBRUARY 2011