KEY TAKEAWAYS
- The Phase 1 & 2 trials aimed to present the latest findings in r/r TCL patients.
- The primary endpoint was to assess safety, tolerability, and ORR. The Secondary endpoint covers CRR, PFS, OS, and DOR.
- The combination showed efficacy in PFS and OS in the r/r TFH subtype of TCL patients and supports further development of this approach.
A diverse and aggressive subset of non-Hodgkin lymphomas is represented by Peripheral T-cell lymphomas (PTCLs). Researchers hypothesized that TCLs may contain mutations in genes responsible for altering immunogenicity and immune escape responses. They theorized that combining pembrolizumab and romidepsin could lead to the elimination of tumors. So, they analyzed and presented the latest findings from this phase I/II trial involving patients with relapsed or refractory TCLs.
In a 21-day cycle of the phase II study, the recommended dose consisted of pembrolizumab at 200 mg administered on day 1, accompanied by romidepsin at a dosage of 14 mg/m2 administered on days 1 and 8.
The study’s primary goals were to assess safety, tolerability, and ORR. The secondary objectives encompassed the evaluation of the complete remission rate (CRR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR).
The intention-to-treat population (ITT) included 38 patients with a median age of 67, with the majority 86.8% being older than 60. The ethnic distribution included 63.2% Whites, 18.4% Blacks, 10.5% Asians, and 7.9% Others. The median number of prior therapies was 2 (range: 1-6), and 81.6% of patients entered the study refractory to previous therapies. Among the patient characteristics, 52.6% had an ECOG performance status of 2, 68.4% exhibited elevated LDH levels, and 63.2% were classified as Stage III or IV.
Grade 3 adverse events were predominantly infections (n=11) and thrombocytopenia (n=10). Hyper-progression occurred in two patients within the initial 10 days of treatment. The ORR was 47.3%, with a complete response (CR) rate of 37.3%. At a median follow-up of 33.5 months, the OS was 21.3 months.
The T follicular helper (TFH) subtype demonstrated a higher ORR than PTCLs numbers. While OS did not vary by age, IPI, or PD-L1 expression, it was significantly higher in the TFH subtype. Two patients with Grade 2 pneumonitis continued treatment after improvement with steroids, and all five patients remained in complete remission (CR).
The results showed that the romidepsin and pembrolizumab combination had better response rates and extended remissions, especially in the r/r TFH subtype of T-cell lymphoma. The promising PFS and OS support the continued development of this approach. Further studies will aim to identify components of the tumor microenvironment (TME) contributing to resistance to immune checkpoint blockade.
Source: https://clml-soho2023.elsevierdigitaledition.com/468/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT03278782
Swaminathan Iyer MD, Rishab Prakash BS, Lei Feng Ph.D., Owhofasa Agbedia MD, Jie Xu MD, Hun Ju Lee MD, Luis Malpica MD, Sairah Ahmed MD, Yasuhiro Oki MD, Dai Chihara MD, Karen Peyton MS, Raphael Steiner MD, Loretta Nastoupil MD, Luis Fayad MD, Francisco Vega MD, Christopher Flowers MD, Sattva Neelapu MD, Ranjit Nair MD. Updated Results of an Investigator-Initiated Phase II Study of Pembrolizumab and Romidepsin for Patients With Relapsed or Refractory T-Cell Lymphoma (TCL) With Survival Analysis.Scopus. 2023; S468-469.
