What is the best treatment for Angioimmunoblastic T-cell Lymphoma (AITL)?

From the Guidelines

The most effective treatment approach for Angioimmunoblastic T-cell Lymphoma (AITL) involves a combination of chemotherapy regimens, such as CHOP, and consideration of autologous stem cell transplantation for eligible patients, as well as novel targeted therapies for relapsed or refractory cases.

Treatment Overview

When considering treatment options for AITL, it's crucial to prioritize approaches that have shown efficacy in improving morbidity, mortality, and quality of life. The treatment typically involves:

• Combination chemotherapy regimens like CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or more intensive protocols such as CHOEP (CHOP plus etoposide) 1.
• For younger, fit patients with high-risk disease, consolidation with autologous stem cell transplantation after achieving remission may improve outcomes 1.

Relapsed or Refractory Cases

For patients with relapsed or refractory AITL, several options can be considered:

• Salvage chemotherapy regimens like ICE (ifosfamide, carboplatin, etoposide) or DHAP (dexamethasone, high-dose cytarabine, cisplatin), followed by stem cell transplantation when possible 1.
• Novel targeted therapies, including histone deacetylase inhibitors like belinostat, which has shown promise in inducing responses across all types of PTCL, with higher response rates in AITL compared to other subtypes 1.
• Bendamustine and cyclosporine have also been identified as effective treatment options for relapsed or refractory AITL, with bendamustine inducing higher response rates in AITL patients compared to those with other subtypes 1.

Individualized Treatment

Treatment should be individualized based on patient age, comorbidities, and disease characteristics, considering the complex immune microenvironment of AITL and the potential for targeted therapies to address specific molecular abnormalities 1.

Key Considerations

• The selection of second-line systemic therapy should consider the patient’s age, performance status, donor availability, agent’s side effect profile, and goals of therapy 1.
• For patients intended for transplant, the choice between single-agent and combination chemotherapy regimens depends on factors such as the intent to transplant soon, the need to sustain response until a suitable donor is identified, and the patient's ability to tolerate intensive treatment 1.

From the FDA Drug Label

Table 5: Response Analysis per Central Assessment Using IWC in Patients with Relapsed or Refractory PTCL Evaluable Patients (N=120) Response RateN (%) (95% CI) CR+PR 31 (25.8) 18.3-34.6 CR 13 (10.8) 5.9-17.8 PR 18 (15.0) 9.1-22. 7 CI=confidence interval, CR=complete response, PR=partial response

Table 4 Baseline Patient Characteristics (PTCL Population) Characteristics Evaluable Patients (N=120) ... PTCL Subtype Based on Central Diagnosis, % PTCL Unspecified (NOS) Angioimmunoblastic T-cell lymphoma (AITL) ALK-1 negative anaplastic large cell lymphoma (ALCL) Other 64 18 11 7

In all evaluable patients (N = 120) treated with Beleodaq, the overall response rate per central review using IWC was 25.8% (N = 31) ( Table 5 ) with rates of 23. 4% for PTCL, NOS and 45.5% for AITL, the two largest subtypes enrolled.

The best treatment for AITL (Angioimmunoblastic T-cell lymphoma) based on the provided drug label is Belinostat (Beleodaq), with a response rate of 45.5% in patients with AITL 2.

From the Research

Treatment Approaches for AITL

• The front-line treatment approach for Angioimmunoblastic T-Cell Lymphoma (AITL) typically involves cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, with consideration for autologous stem-cell transplant (SCT) 3.
• In the relapsed and refractory settings, allogeneic SCT offers the chance for long-term remission, and the choice of treatment depends on whether an allogeneic SCT is planned 3.
• Agents with preferential activity in relapsed or refractory AITL include epigenetic modifiers such as histone deacetylase inhibitors and hypomethylating agents, as well as targeted agents like brentuximab vedotin and phosphoinositide-3-kinase inhibitors 3.

Alternative Treatment Options

• Cyclosporine has been shown to be effective in treating AITL, with an overall response rate of 86% in second or later lines, suggesting its utility in heavily treated cases, including those who underwent HSCT 4.
• The addition of etoposide to CHOP chemotherapy (CHOEP) has been associated with improved overall survival (OS) in patients with stage II to IV PTCL, including AITL 5.
• Consolidation with autologous stem cell transplantation (ASCT) has been shown to improve 5-year OS in patients with advanced-stage AITL, regardless of whether complete remission was achieved 5.

Ongoing Research and Future Directions

• Ongoing studies are evaluating new potential targets for AITL, with a focus on identifying markers of response and resistance, and incorporating novel agents into front-line treatment 3.
• Clinical trials are investigating the use of recently approved drugs with known activity in AITL, paired with induction regimens, to demonstrate long-term progression-free survival over traditional chemotherapy regimens 6.