IACH 2018 | Treatment of adult T-cell leukemia/lymphoma

The 1st Annual Meeting of the International Academy for Clinical Hematology (IACH) took place in Paris, France, on September 27–29, 2018. On Friday 28 September, a non-Hodgkin lymphoma session was held, with an abstract presented entitled “Therapy of HTLV-related lymphoma” by Professor Ali Bazarbachi from the American University of Beirut Medical Center, Beirut, Lebanon.

Adult T-cell leukemia/lymphoma (ATL), a rare aggressive T-cell malignancy often caused by human T-cell lymphotropic virus type-1 (HTLV-1), is associated with inferior outcomes due to resistance to chemotherapy. According to previous observations, leukemogenesis of ATL is a staged process containing several factors that result in increased proliferation of T lymphocytes. HTLV-1 is an endemic retrovirus present in certain areas of the world, its ATL virulence is around 2–4%.

To date, there is no standard of care for patients with ATL. Enrolment in clinical studies is always recommended. Administration of dose-intense multi-agent chemotherapy may improve outcomes in the lymphoma subtype.  However, the most efficient survival rates were observed in patients receiving antiviral therapy using the combination of zidovudine and interferon-alpha and in patients receiving allogeneic bone marrow transplantation. A number of new therapy options are being investigated in ongoing prospective trials.

Subtypes of ATL:
  • Aggressive ATL
    • Acute ATL: 60% of all patients
    • Lymphomatous ATL: 20% of all patients
  • Indolent ATL
    • Smoldering ATL
    • Chronic ATL
Current treatment strategies:
  • Chemotherapy (LSG15) with or without mogamulizumab:
    • In this study, newly diagnosed ATL patients (acute, lymphoma, or unfavorable chronic) received LSG15 plus mogamulizumab or LSG15 alone2
    • Complete response (CR): 52% (95% CI, 33–71%) LSG15 with magamulizumab vs 33% (95% CI, 16–55%) LSG15 alone
    • No difference in median progression-free survival (PFS): 8.5 months vs 6.3 months in the LSG15-plus-mogamulizumab and LSG15 only groups, respectively (NS)
  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
    • Allo-HSCT is effective with myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) increasing long-term survival in selected patients with ATL3
    • Allo-SCT but not auto-SCT can be a feasible salvage option for ATL patients, particularly those transplanted in CR1. In this study, patients had a 3-year OS of 34.3% (95% CI, 15.5–67.2)4
    • Allo-HSCT is an option for patients with acute and lymphoma subtypes
    • Allo-HSCT in first remission yields better overall survival rates
    • Potentially curative therapy option in one-third of transplanted patients
    • Mogamulizumab given prior to allo-HSCT may increase morbidity and mortality
  • Zidovudine (AZT) plus interferon-alpha (IFN)
    • This antiviral combination therapy improves survival in smoldering-, chronic-, and TP53 negative acute ATL with a 5-year OS of 46% as compared to 12% with chemotherapy, P = 0.0045
    • AZT/IFN should be considered as first-line therapy
    • AZT/IFN should be used alone as first line therapy in leukemic forms of ATL, not after several lines of chemotherapy
    • AZT/IFN therapy is better if it is given in higher doses because lower doses are usually not effective
  • Chemotherapy
    • Chemotherapy can be combined with AZT/IFN antiviral regimen
    • First-line antiviral therapy is less effective than first-line chemotherapy in ATL lymphoma5
    • Prevention of opportunistic pathogens is important
  • Arsenic trioxide (As) plus IFN/AZT
    • In a phase II study, As plus IFN/AZT showed superior response rates with a manageable toxicity profile in patients with chronic ATL, 100% response rate was observed6
    • Preclinical findings suggest that the addition of AS to AZT/IFN regimen as consolidation therapy may eliminate leukemia-initiating cells7

Professor Bazarbachi concluded that the combination of AZT and IFN has superior efficacy in leukemic subtypes of ATL and is a promising first-line therapy option in patients with adult T-cell leukemia/lymphoma. He highlighted that in order to prevent the occurrence of resistance and relapse, further clinical studies are underway to evaluate adding other targeted therapies, including arsenic/IFN combination therapy or monoclonal antibodies. He further added that allo-HSCT is effective in selected patients.

 

References
  1. Bazarbachi A. How I treat ATL. 1st Annual Meeting of the International Academy for Clinical Hematology (IACH), Paris, France. Slides were provided to the Lymphoma Hub by Ali Bazarbachi.
  2. Ishida T. et al. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. British Journal of Haematology. 2015 Jun; 169(5):672–82. DOI: 10.1111/bjh.13338. [Epub 2015 Mar 2].
  3. Ishida T. et al. Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. 2012 Aug 23; 120(8):1734–41. DOI: 10.1182/blood-2012-03-414490. [Epub 2012 Jun 11].
  4. Bazarbachi A. et al. Outcome of patients with HTLV-1-associated adult T-cell leukemia/lymphoma after SCT: a retrospective study by the EBMT LWP. Bone Marrow Transplantion. 2014 Oct; 49(10):1266–8. DOI: 10.1038/bmt.2014.143. [Epub 2014 Jul 14].
  5. Bazarbachi A. et al. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. Journal of Clinical Oncology2010 Sep 20; 28(27):4177–83. DOI: 10.1200/JCO.2010.28.0669. [Epub 2010 Jun 28].
  6. Kchour G. et al. Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL). Blood. 2009;113(26):6528-6532.
  7. Bazarbachi A. et al. How I treat adult T-cell leukemia/lymphoma. 2011 Aug 18;118(7):1736-45. DOI: 10.1182/blood-2011-03-345702. [Epub 2011 Jun 14].
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