Not only is there is a severe lack of effective T-cell lymphoma (TCL) treatments, according to GlobalData — a sentiment reflected by key opinion leaders (KOLs) — but the leading data and analytics company does not expect any significant solutions to appear in the next decade.

Sakis Paliouras, PhD, Senior Oncology Analyst at GlobalData, comments: “The currently available treatments for TCL only offer temporary benefit, often at the expense of side effects such as mucositis, gastrointestinal and cardiac toxicity. While KOLs have highlighted various areas that could be improved, an analysis of the pipeline shows that it is unlikely that we will see huge advancement in the next ten years.”

One key unmet need is found in the cutaneous TCL (CTCL) subtype. Early-stage CTCL has a favorable 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.

Paliouras continues: “An improvement in systemic treatment options is the most important unmet need for CTCL. While the two novel drugs in the pipeline — Affimed’s AFM-13 for CD30+ patients and Innate Pharm’s first-in-class anti-KIR3DL2 antibody lacutamab — may offer some benefit, they are unlikely to significantly change the treatment paradigm of the disease, providing a progression-free survival that is on par with other available agents.”

There is also a significant unmet need for patients with another subtype, peripheral TCL (PTCL), that relapse or are refractory to frontline therapy. These patients have very poor five-year outcomes, and their response to available treatments are usually not durable and disease progression rates are high.

Paliouras adds: “While the majority of the TCL pipeline is focused on relapsed/refractory (R/R) PTCL patients, only a couple of agents have generated significant KOL enthusiasm. Some promising options include Secura Bio’s PI3K-delta inhibitor Copiktra (duvelisib) and Daiichi Sankyo’s EZH1/2 inhibitor valemetostat. Novel pipeline agents would have to be either biomarker-driven, or to have a high response rate across subtypes in order to demonstrate high potential in this setting.”

Other unmet needs for TCL are not labeled as ‘high importance’ — these include identifying maintenance regimens for patients in first remission; new clinical trials that focus on combinational approaches; and biomarker-restricted trials that can capitalize on already-identified molecular targets and move TCL treatment into a more personalized approach.

Paliouras continues: “The only current agents in TCL that are biomarker restricted are Adcetris, for CD30+ patients and ALK inhibitors for ALK+ patients. For a personalized treatment future in TCL, more biomarkers that match a patient to the ideal treatment regimen are warranted.”

Not only are TCL patients underserved, but there is also a huge geographic disparity in terms of access to treatment. Patients with CTCL and PTCL in the US have numerous drugs available that were never approved in other markets — most notably in the EU.

Paliouras adds: “EU-based KOLs have raised numerous complaints about the disparity in the availability of CTL treatments between the EU and the US, especially the complete lack of HDAC inhibitors (Istodax, Beleodaq, and Zolinza) in the EU, which the EMA has rejected due to a more stringent review of their pivotal clinical trials, compared to a more flexible review by the FDA.”