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 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.
- 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.
- 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].
- 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].
- 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].
- 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].
- 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.
- 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].