In short
When angioimmunoblastic T-cell lymphoma does not respond to treatment or when the response does not last long, patients face complex decisions about next steps. Understanding what refractory disease means and what treatment options are available can help patients navigate this challenging situation.
What Does Refractory Mean?
The term "refractory" is used to describe when angioimmunoblastic T-cell lymphoma (AITL) does not respond to treatment, meaning that the cancer cells continue to grow. This is different from relapsed disease, where the lymphoma reappears or grows again after a period of remission (a time when the disease is under control or cannot be detected).
In some cases, the lymphoma may respond to treatment initially, but the response does not last very long. This situation is also considered refractory disease. Treatment can be challenging because AITL frequently relapses after initial and subsequent therapy.
Treatment Options for Refractory Disease
When AITL becomes refractory to treatment, several drugs that are used for other types of lymphoma may be considered. The choice of treatment for refractory disease often depends on whether an allogeneic stem cell transplant (a procedure where stem cells from a donor are used to replace a patient's blood-forming cells) is planned.
Some drugs that may be used for patients with AITL that has relapsed or is refractory to other treatments include:
- Alemtuzumab (Campath)
- Bendamustine (Treanda)
- Bortezomib (Velcade)
- Cyclosporine
- Fludarabine (Fludara)
- Gemcitabine (Gemzar)
- Pralatrexate (Folotyn)
- Rituximab (Rituxan)
- Romidepsin (Istodax)
- Belinostat (Beleodaq)
Stem Cell Transplantation
In the relapsed and refractory settings, allogeneic stem cell transplant offers the chance for long-term remission. An allogeneic transplant uses stem cells from a healthy donor to help rebuild the patient's immune system and blood cells. This approach can provide better long-term control of the disease compared to other treatment options.
The decision about whether to pursue an allogeneic stem cell transplant is an important one that affects which other treatments are chosen. If a transplant is being planned, the treatments used beforehand may be selected specifically to prepare the patient for this procedure.
Novel and Targeted Therapies
Agents with preferential activity in relapsed or refractory AITL include epigenetic modifiers (drugs that change how genes are turned on or off in cancer cells). These include histone deacetylase inhibitors (drugs that help restore normal gene function) and hypomethylating agents (drugs that can reactivate genes that have been silenced in cancer cells).
Other targeted agents show promise in AITL. These include brentuximab vedotin and phosphoinositide-3-kinase inhibitors (drugs that block specific signals that cancer cells use to grow). Ongoing studies are evaluating new potential targets for AITL, with particular focus on identifying markers of response and resistance.
A prospective study evaluated a combination of rituximab, lenalidomide, and chidamide for patients with relapsed or refractory AITL. In this study, the overall response rate was 75%, with 20.8% of patients achieving complete remission. The median progression-free survival was 10.8 months. While some side effects occurred, including low blood cell counts, pneumonia, and skin rash, the treatment was generally manageable.
Additional studies are assessing the incorporation of novel agents into treatment approaches. These studies aim to lead to more individualized treatment approaches and, ultimately, improved outcomes for patients with AITL.
