What does the evidence suggest about the oncogenic role of HIV in BL?  

Dr Kaplan: These data are not that strong. There are in vitro data suggesting that the HIV Tat protein [that] circulates in HIV-infected individuals can activate an enzyme that causes DNA damage in both MYC and IGH and co-localize these genes in the cell nucleus. When DNA repair then occurs, there may be greater likelihood of MYC-IGH translocations, which are pathogenic in BL. The data offer no real therapeutic utility at this point.

Dr Reid: Incidence of BL is increased in the setting of HIV. In the United States, Epstein-Barr virus (EBV) is more commonly present with HIV-BL than non-HIV-associated BL. This supports immune dysregulation due to HIV infection contributing to EBV-mediated oncogenesis.    

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What are some special considerations that oncologists should keep in mind when managing patients with HIV?

Dr Kaplan: Key considerations are as follows:

  • Good HIV viral load control is important when using chemotherapy. 
  • Antiretrovirals should almost always be given along with lymphoma therapies.
  • Antiviral regimens with the fewest drug–drug interactions should be used — usually integrase inhibitor-based regimens.
  • Be sure to include neutropenic antibiotic prophylaxis as well as [Pneumocystis jiroveci pneumonia] prophylaxis.
  • If using rituximab in patients with lymphoma who have very low CD4 counts (<50), be particularly vigilant about monitoring for infection as these patients are at high risk.

Dr Reid: BL in the setting of HIV is more likely to present with high-risk disease including CNS involvement. In this setting, regimens with CNS penetration like R-CODOX-M/IVAC along with intrathecal therapy may be optimal when feasible. Advanced HIV/AIDS is likely to be associated with higher risk of infectious complications, necessitating aggressive prophylaxis and monitoring for opportunistic infections and febrile neutropenia.

Finally, collaboration with providers and pharmacists with expertise in ART is important to choose an ART regimen compatible with chemotherapy in terms of drug–drug interactions as well as overlapping toxicities. In general, strong CYP-3A4 inhibitors including boosters such as ritonavir and cobicistat should be avoided, as should [azidothymidine] due to myelosuppression. The [National Comprehensive Cancer Network] guidelines for “Cancer in People Living with HIV” is a resource addressing these and other issues relevant to managing cancer in persons living with HIV.6

What should be the focus of future research in this area?

Dr Kaplan: There is a need for novel targeted therapies for refractory disease, as well as more studies of ways in which to target MYC or surrogate genes/proteins – for example, bromodomain inhibitors (BETs).

Dr Reid: There are 2 major points here: Additional studies to determine the best upfront therapy, which is likely to vary by presenting clinical or genomic features, are needed. There is an ongoing phase 3 study comparing [R-CODOX-M/IVAC] and DA-EPOCH-R in high-risk BL patients, which will be helpful in directly comparing these regimens.

Additional studies evaluating clinical and genomic factors predictive of long-term disease-free survival will be helpful in further stratifying patients, predicting those who may require more intensive regimens than DA-EPOCH-R to achieve cure. Optimal strategies to improve outcomes in the setting of CNS involvement are needed, but for now I would favor [R-CODOX-M/IVAC] over DA-EPOCH-R given better CNS penetration of the regimen. 

Management of relapsed or refractory disease [represents another area of need]. Currently, there is not an effective second-line strategy for BL; only rarely is relapsed or refractory disease durably responsive. Because there are only the very rare “second chances” with this disease, optimizing front-line therapy is critical as noted above. Novel therapeutic strategies are desperately needed for patients with relapsed or refractory disease. A major oncogene in BL, C-MYC, [codes for c-Myc], a transcription factor that is considered essentially “undruggable” – no effective targeted therapies have been developed. Strategies targeting pathways downstream of c-Myc could be promising but will likely require a multipronged approach.


  1. Roschewski M, Dunleavy K, Abramson JS, et al. Multicenter study of risk-adapted therapy with dose-adjusted EPOCH-R in adults with untreated Burkitt lymphomaJ Clin Oncol. 2020;38(22):2519-2529. doi:10.1200/JCO.20.00303
  2. Atallah-Yunes SA, Murphy DJ, Noy A. HIV-associated Burkitt lymphoma. Lancet Haematol. 2020;7(8):E594-E600. doi:10.1016/S2352-3026(20)30126-5
  3. Ribrag V, Koscielny S, Bosq J, et al. Rituximab and dose-dense chemotherapy for adults with Burkitt’s lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10036):2402-2411. doi:10.1016/S0140-6736(15)01317-3
  4. Noy A, Lee JY, Cesarman E, et al. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphomaBlood. 2015;126(2):160-166. doi:10.1182/blood-2015-01-623900
  5. Dunleavy K, Pittaluga S, Shovlin M, et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369(20):1915-1925. doi:10.1056/NEJMoa1308392
  6. Reid E, Suneja G, Ambinder RF, et al. Cancer in people living with HIV, version 1.2018, NCCN Clinical Practice Guidelines in OncologyJ Natl Compr Canc Netw. 2018;16(8):986-1017. doi:10.6004/jnccn.2018.0066

This article originally appeared on Hematology Advisor