T-cell lymphomas (TCL) are a rare type of non-Hodgkin lymphomas, divided into cutaneous (CTCL) and peripheral (PTCL) subtypes. Key opinion leaders (KOLs) interviewed by GlobalData believe that there is a high level of unmet need across the board in TCLs as there have been no new agents that dramatically improve the outcome of these patients in the last 20 years. On average, both progression-free survival (PFS) and overall survival (OS) in TCL patients remains relatively short. The only exception to this is in the peripheral anaplastic large-cell lymphoma (ALCL) subtype, as upfront chemotherapy in combination with Seagen’s/Takeda’s Adcetris (brentuximab vedotin) leads to a notable number of cures.
In the CTCL subtype, early stage disease has a favourable prognosis and is mainly treated with skin-directed therapies. However, when there is late-stage presentation and a need for systemic therapies, all systemic therapy options are poor, highlighting the most important CTCL unmet need (Figure 1). All systemic CTCL therapies are characterised by a low overall response rate and are not biomarker-defined, exposing most patients who will not derive a benefit to unnecessary toxicities. The pipeline for TCLs is a lot more focused on PTCL, leaving CTCL patients with only two novel monoclonal antibodies: Affimed’s AFM-13 for CD30+ patients and Innate Pharm’s first-in-class anti-KIR3DL2 antibody lacutamab. While these agents may offer substantial benefit, they are unlikely to transform the systemic treatment segment of CTCL so this unmet need will remain partially unaddressed in the near future.
AITL = angioimmunoblastic T-cell lymphoma
In PTCL, chief among the unmet needs is patients who are either primarily refractory or who relapse early after first-line treatment. These patients have very poor five-year outcomes, and while some available agents can offer a PFS advantage, their responses are usually not durable and progression rates are high. While the majority of the TCL pipeline is focused on relapsed/refractory (R/R) PTCL patients, only a few of the agents have generated significant KOL enthusiasm, such as Secura Bio’s PI3K-delta inhibitor Copiktra (duvelisib) and Daiichi Sankyo’s EZH1/2 inhibitor valemetostat. While these agents are expected to partially address the unmet needs in this segment, KOLs do not expect to see a fundamental change in the way R/R PTCL patients are treated in the next ten years.
The remaining unmet needs include the need to identify maintenance regimens for PTCL patients who are in remission, new clinical trials that focus on combinational approaches, and biomarker-restricted trials that can capitalise on already-identified molecular targets and move TCL treatment into a more personalised approach. Of these, the need for personalised approaches is the one expected to be mostly addressed in the future, with three targeted agents in the late-stage pipeline and numerous such approaches in the early-stage pipeline, including CAR-T cells.