Phase II trial of atezolizumab (anti-PD-L1) in the treatment of stage IIb–IVB mycosis fungoides/Sézary syndrome patients relapsed/refractory after a previous systemic treatment (PARCT)

Treatment of advanced mycosis fungoides (MF) and Sézary syndrome (SS) remains a clinical challenge. Atezolizumab blocks a protein called PD-L1 (programmed death-ligand 1) from binding to its receptor found on the surface of immune cells and tumor cells. It helps to restore the immune activity of the body against the cancer. Atezolizumab is already used to treat adults with a range of solid tumors including cancer that affects the bladder and the urinary system, called urothelial carcinoma, and a cancer that affects the lungs, called non-small cell lung cancer. The primary objective is to determine the antitumor activity of atezolizumab for patients with refractory or relapsed advanced stages of mycosis fungoides and Sézary syndrome, assessed in term of the overall response rate (ORR), the proportion of patients who achieve a complete response (CR) or partial response (PR), according to EORTC-ISCL-USCLC criteria. This is an international, multi-center, open label phase II trial where patients with stage IIb–IVB mycosis fungoides/Sézary syndrome, who have relapsed/refractory after a previous systemic treatment will be treated with atezolizumab. Main inclusion criteria: Male or female patients with diagnosis of CTCL (mycosis fungoides or Sézary-Syndrome) tumor stage IIB to IVB, availability of tumor sample for evaluation of PD-L1 expression, inadequate response or secondary treatment failure to at least 1 prior systemic therapy for CTCL according to treatment guidelines (e.g. INF-2α or bexarotene), age ≥18 years old and WHO performance status 0–1 In this single arm phase II trial, patients received atezolizumab 1200 mg IV Q3w for 1 year since start of first protocol treatment administration unless clinically relevant disease progression or other withdrawal criteria were met. Those patients for whom a clinical benefit were documentable at 1 year were given the possibility to prolong the treatment for a maximum of two additional years unless a withdrawal criterion occurs earlier. A total of 26 patients were registered by 7 institutions in 7 countries between 23rd October 2018 and 16th September 2019. Nine of the 26 patients did not meet the eligibility criteria due to ongoing treatment with a Retinoid, wash out of Bexaroten not respected, Prostate adenocarcinoma, uncontrolled Diabetes in two cases, Tuberculosis infection 2 cases and Deep venous thrombosis resolved one week before enrollment. The median age of the 17 eligible patients was 66 years, ranging between 52 and 82 years Most patients had mycosis fungoides (70.6%) and stage IIB disease (41.2%). All 17 eligible patients were reported to have other medical conditions at trial entry. The median follow-up over the 26 enrolled patients is of 19.6 months with IQR corresponding to 17.1–21.4 months. Of the 26 patients who were administered atezolizumab, three patients were still on treatment at the time of database lock. More than half (57.7%) received at least 4 cycles of atezolizumab. The median number of cycles for all patients is 5 (range: 1–31). Nine (34.6%) of the 26 who received atezolizumab experienced a schedule modification (treatment delayed. The median duration of treatment was 15 weeks, ranging from 3 to 96. Twelve patients (46.2%) received treatment with a relative dose intensity (RDI) between 80 and 100%, while 14 patients (53.8%) received treatment with a RDI ≥100%. The median RDI was 100% (range: 84.4–102.4%). The proportion of responders (CR or PR) observed within 1 year since registration was 15.4% (4 patients) in the intention-to-treat population. Ten (38.5%) patients showed stable disease, 6 progression (23.1%), 3 were not evaluable and 3 (11.5%) experienced early death. the per-protocol population, median PFS was 3 months (95% CI 1.4–4.9), median time to next systemic treatment was 5.9 months (95% CI 2.8–NE) and median OS was not reached. The main reason for going off treatment in this trial was disease progression (50%). There were 4 cases (7.7%) of stopping protocol treatment due to toxicity. The most frequent grade ≥3 AE was sepsis, affecting four patients (15.4%), including two leading to death, one of them considered to be possibly related to protocol treatment. In summary: Atezolizumab showed moderate activity in pretreated advanced cutaneous T-cell lymphoma. It will be of interest to further analyze which subpopulation of MF patients profits from atezolizumab. Table 1(abstract Tre-O2-11). Treatment activity: primary endpoint overall response rate (ORR) Decision rule N (%) Per-protocol population (N=17) ORR status within 1 year since registration Success 3 (17.6) Failure 14 (82.4) Best overall response with 1 year from registration Partial response 3 (17.6) Stable disease 7 (41.2) Progression 5 (29.4) Not evaluable 1 (5.9) Early death 1 (5.9) Intention-to-treat population (N=26) ORR status within 1 year since registration Success 4 (15.4) Failure 22 (84.6) Best overall response with 1 year from registration Partial response 4 (15.4) Stable disease 10 (38.5) Progression 6 (23.1) Not evaluable 3 (11.5) Early death 3 (11.5) Open table in a new tab