Romidepsin has significant and sustainable single-agent activity (including improvement in pruritus) and an acceptable safety profile, making it an important therapeutic option for treatment refractory CTCL.

Both patients were men with nodular lesions on the face. Histologically, the lesions were composed predominantly of variably maturated plasma cells with monotypic expression of immunoglobulin (Ig) lambda chains. Polymerase chain reaction for IgH genes did not reveal clonal rearrangement. Our cases are discussed in the context of previously reported cases of PCP with a long-term follow-up. We also include a review of all cases of PCP with known tumor progression earlier in the course of the disease (local relapse or visceral spread) to determine the clinical course of this primary cutaneous lymphoma.

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Introduction: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. Methods: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a C 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P \ 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming.

Background: Responses to romidepsin, a novel pan-HDAC inhibitor, have been observed in patients (pts) with cutaneous T-cell Lymphoma (CTCL). This Phase 2B, singlearm, open-label registration study enrolled pts with CTCL (Stages IB–IVA) at 33 European and US sites. Pts with histologically confirmed CTCL who failed ≥1 prior systemic therapy, had adequate organ function, and ECOG PS 0 or 1 were eligible. Exclusions included significant cardiovascular abnormality or treatment with QTc-prolonging or CYP3A4-inhibiting drugs. Pts received romidepsin 14 mg/m2 as a 4-hr IV infusion on days 1, 8, and 15 every 28 days for up to 6 cycles (extended for stable disease or response). Aim: The primary endpoint was the response rate among evaluable pts, measured by a combination of a weighted scoring instrument to determine skin involvement (SWAT), imaging, and circulating Sézary cells (as applicable). Results: 96 pts were enrolled and received romidepsin (as-treated); 72 (75%) were evaluable (≥2 cycles) for efficacy. Enrollment is complete, 4 pts with confirmed PR continue to receive romidepsin on extended treatment, 5 pts off-treatment are being followed. Mean age of all pts was 57±12 yrs, and median time since diagnosis was 3 yrs (range <1–26). 68 pts (71%) had disease stage ≥IIB. Median number of prior systemic therapies was 2 (range 1–8). Response (assessed by investigators) and pruritus relief (assessed by visual analog scale [VAS]) data are in the table. Objective disease response rate (ORR) was not lower in pts with advanced-stage disease; 23 (47.9%) of 48 pts with stage IIB-IVA and 7 (29%) of 24 pts with stage IB-IIA achieved OR. With a median follow-up of 5.3 months (mo), median duration of response has not been reached. 50% of responders (evaluable pts) have maintained a response for ≥5 mo and 30% for ≥8 mo. The maximum duration of response was 19.8 mo. 24 (80%) of the 30 pts with a response had not progressed as of the last assessment. Most pts (48/52; 92%) with pruritus at baseline (≥30 mm on VAS) had some relief, including most of those with severe pruritus. Adverse events (AEs) occurred in 93 pts (97%). AEs reported in ≥20% of pts were nausea (56%), asthenia (52%), vomiting (29%), anorexia (23%), hypomagnesemia (21%), and pyrexia (20%). AEs ≥ grade 3 occurred in 32 pts (33%), most commonly fatigue (7%), disease progression (4%), and pyrexia (4%). 21 pts (22%) had a serious AE; the most frequently reported serious AEs were disease progression (6%), pyrexia (3%), sepsis (2%), tumor lysis syndrome (2%), and hypotension (2%). 20 pts (21%) withdrew because of AEs, including fatigue (4%), pyrexia (2%), prolonged QT (2%), and CTCL progression (2%). 6 pts (6%) died, 1 possibly related to treatment. Mean QTcF change from baseline to 2 hrs post-dose was 4.6 msec using baseline assessments before any anti-emetics and 1.3 msec using baseline assessment after anti-emetics. No pts had QTcF values >500 msec. Conclusions: This study shows clinical benefit associated with romidepsin use in treatment-refractory CTCL, with pts achieving durable response and relief from pruritus. Toxicities associated with romidepsin were tolerable and manageable. Evaluable Pts N=72 As-treated Pts N=96 a stable disease for ≥90 days b relief = ≥ 30mm decrease on 100mm VAS or score of 0 for 2 consecutive cycles Confirmed ORR 42% 34% PR, n (%) 24 (33%) 27 (28%) CCR, n (%) 6 (8%) 6 (6%) SD90a, n (%) 26 (36%) 28 (29%) Overall disease control (CCR+PR+SD90) 56 (78%) 61 (64%) Median time (mo) to response (range) 1.9 (0.9–4.8) 1.9 (0.9–4.8) Median time (mo) to disease progression (range) 9.0 (2.7–21.7) 8.3 (0–21.7) Confirmed OR in stage ≥ IIB, n (%) 23/48 (48%) 26/68 (38%) Relief of pruritusb, n (%) 25/52 (48%) NA Relief of severe pruritus, n (%) 16/29 (55%) NA