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J.A. Sparano et al.
ABC
Figure 2. Kaplan-Meier estimates of outcomes in patients achieving complete response to response-adapted EPOCH chemotherapy, stratified by number of treat- ment cycles. (A-C) Patients are stratified into two groups: a group that received four or fewer cycles of EPOCH chemotherapy and a group that received five or six cycles. Estimates are shown for event-free survival (A), time to progression (B) and overall survival (C).
lymphoma subtype and consider other molecular charac- teristics that have prognostic relevance.24
Interim restaging is recommended to identify patients whose disease has not responded well to, or has pro- gressed, on induction therapy after two to four cycles of therapy.2 Staging is recommended using FDG-PET inte- grated with CT (FDG-PET/CT) at diagnosis, after two to four cycles of therapy, and at the end of treatment.2 A negative PET scan after two to four cycles of induction therapy has been associated with significantly higher event-free survival and overall survival rates in some studies,25-28 but not others.29-32 Although several studies failed to show improvement in clinical outcomes when therapy was tailored to FDG-PET/CT response,33,34 these studies were designed to evaluate more aggressive thera- py in patients with persistent FDG-avid lesions, not de- escalation of therapy in patients who had an early FDG response. Differentiation of reactive adenopathy from active lymphoma may be challenging in patients with HIV-associated lymphoma, although this may be less problematic in patients with well-controlled viremia.35 Although preliminary results reported by Dunleavy et al.23 regarding use of interim FDG-PET/CT as a pharmacody- namic biomarker for tailoring de-escalation appears promising in HIV-associated lymphoma, further study is required in multicenter prospective clinical trials.
Our analysis has several strengths and limitations. The strengths include the prospective nature of the trial, and the protocol-specified guidelines for treatment duration based on radiographic response. The limitations include the post-hoc analysis examining response durability based on rapidity of response and number of treatment cycles, and the fact that the observations were not based on an adequately powered comparison between the stan-
dard approach of six treatment cycles compared with a risk-adapted approach. Nevertheless, given recent evi- dence that four cycles of R-CHOP constitute adequate therapy for a low-risk population,4 the findings of our study indicating the feasibility of a response-adapted de- escalation strategy in a higher-risk population with HIV- associated lymphoma, and the clinical utility of interim FDG/PET, there is now a compelling rationale to prospec- tively evaluate the use of interim FDG-PET/CT after two cycles of therapy, rather than CT as used in our trial, in order to assess response to guide treatment duration in patients with HIV-associated lymphoma.
Disclosures
No conflicts of interest to disclose.
Contributions
The manuscript was written by JAS and was approved by all co-authors. The clinical protocol was written by JAS, JYL, and LDK. The data and statistical analyses were performed by JYL and administrative support and oversight were provided by RM. Pathological review of tumor specimens was performed by EC and AC. Individuals who contributed subjects to the trial included JAS, LDK, JCR, RFA, DA, AN, DHH, LR, EC, WW, and AC.
Acknowledgments
This study was coordinated by the AIDS Malignancy Consortium (Ronald Mitsuyasu, MD, Chair).
Funding
This study was supported in part by Public Health Service grant n. UM1CA121947, the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services.
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haematologica | 2021; 106(3)