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Intense chemotherapy regimens was tolerated by and yielded favorable outcomes in adult patients with HIV-associated Burkitt lymphoma (HIV-BL), according to study results presented by Juan Pablo Alderuccio, MD, of the University of Miami School of Medicine, in Miami, Florida, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“Adult Burkitt lymphoma accounts for 40% of all HIV-related lymphomas,” said Dr Alderuccio. “Prognostic factors and optimum treatment strategies remain unclear, and current recommendations are based on small studies.”
The retrospective multicenter analysis of 249 patients with newly diagnosed HIV-BL included data from a subcohort of US-based patients from a recent study (n=140) and from patients treated at centers in the United Kingdom between 2009 and 2018 (n=109). Outcomes of interest were estimated progression-free (PFS) and overall survival (OS), and baseline characteristics were evaluated for prognostic value.
Median patient age was 43 years (interquartile range [IQR], 35-50), and the majority of patients were men (84%). At diagnosis, 55% of patients had detectable HIV viral loads, and 39% of patients were receiving combination antiretroviral therapy.
Most clinical features evaluated at baseline were similar between the groups, including lactate dehydrogenase (LDH) levels and CD4 counts. Clinical features that were significantly different between the US and UK groups included Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 4 (32% vs 65%; P <.001), MYC rearrangement (92% vs 99%; P <.001), and central nervous system (CNS) involvement (30% vs 17%; P =.026).
Study patients underwent the following treatment regimens: cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate alternating with ifosfamide, etoposide, high-dose cytarabine (CODOX-M/IVAC; also known as Magrath, 60%); dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH, 25%); fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (HyperCVAD/MA, 13%); as well as other treatments (~1%). Most patients (87%) also received rituximab. Similar regimens were used in cases of CNS involvement.
Treatment differed between the US-based and UK-based groups. In the United States, most patients received DA-EPOCH (42%), followed by CODOX-M/IVAC (32%) and HyperCVAD/MA (24%). In the United Kingdom, 96% of patients received CODOX-M/IVAC, and the remainder of patients received DA-EPOCH. Patients in the United States were more frequently administered rituximab compared with those in the UK (94% vs 79%, P <.001). Patients with lower median CD4 count were more likely to receive CODOX-M/IVAC or HyperCVAD/MA compared with DA-EPOCH (144 vs 260 cells/µL; P =.04).
Complete response and partial response were achieved by 70% and 9% of patients, respectively; 14% experienced disease progression, and approximately 7% were not evaluable. Treatment-related mortality was 10%.
Median follow-up duration was 4.5 years, and 3-year PFS and OS were 61% and 66%, respectively. Patients with higher CD4 counts (>100 cells/µL) had higher 3-year PFS and OS rates compared with those with lower CD4 counts (68% vs 57%, respectively; P =.03). Neither 3-year PFS nor OS differed based upon treatment received or with/without rituximab.
Relapse of HIV-BL occurred in 34% of patients (23% systemic only; 11% CNS). A higher incidence of CNS relapse was observed with DA-EPOCH compared with all other regimens (P =.032).
In a multivariable analysis, factors associated with PFS and OS were ECOG performance status of 2 to 4 (PFS: HR, 1.87; P =.007; OS: HR, 2.00; P =.006); baseline CNS involvement (PFS: HR, 1.70; P =.023; OS: HR, 1.83; P =.015); LDH more than 5 times the upper limit of normal (PFS: HR, 2.09; P =.001; OS: HR, 2.26; P =.001); and more than 1 extranodal site (PFS: HR, 1.58; P =.043; OS: HR, 1.71; P =.027). After adjusting for all of the prognostic variables, treatment with CODOX-M/IVAC was associated with longer PFS (adjusted HR, 0.45; P =.005) and OS than the other regimens (adjusted HR, 0.44; P =.007).
“This study represents the largest analysis in HIV-associated Burkitt lymphoma to date,” concluded Dr Alderuccio. “Favorable tolerance and outcomes were observed with intense chemotherapy regimens such as CODOX-M and IVAC.”
Limitations of the study include the retrospective design and possible selection bias.
Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
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Alderuccio JP, Olszewski AJ, Evens AM, et al. Prognostication, survival and treatment-related outcomes in HIV-associated Burkitt lymphoma (HIV-BL): a US and UK collaborative analysis. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 706.