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Risk-adapted R-EPOCH in DLBCL
all 64 patients who achieved a complete response. Among the 24 who received four or fewer cycles, five received fewer than four cycles. The reasons for this were disease progression after achieving a complete response (n=1), physician’s decision (n=1), or other reasons (n=3). Among the 40 who received five or six cycles of EPOCH, 36
Table 1. Characteristics of the entire population and complete responders strat- ified by number of EPOCH treatment cycles.
received six cycles and four received five cycles due to physicians’ decision (n=3) or unknown reasons (n=1).
Clinical outcomes by number of EPOCH treatment cycles in complete responders
Outcome data for the 106 patients in the entire study population, and the 64 patients who achieved complete response are shown in Table 2 and Figure 2A-C. After a median follow-up of 30 months (range, 0-67 months) for all treated patients, 36 (34%, 95% CI: 25%-44%) died, with relapsed lymphoma being the cause of death in eight (8%, 95% CI: 3%-14%). After a median follow-up of 38.5 months (range, 1-66 months) in the 64 patients who achieved a complete response, 11 (17%, 95% CI: 9%- 29%) died, five (8%, 95% CI: 3%-18%) with relapsed lymphoma as the cause of death. Outcomes were similar for those treated with four or fewer cycles compared with those given five or six cycles with respect to rates of 2- year event-free survival (78% vs. 85%), time to progres- sion (91% vs. 87%), and overall survival (78% vs. 90%).
Discussion
In the absence of prospective comparative data in HIV- associated lymphoma, six cycles of rituximab plus infu- sional EPOCH is considered a preferred regimen for first- line treatment of HIV-associated DLBCL, HHV8-positive DLBCL, primary effusion lymphoma, and is also among the preferred regimens for HIV-associated Burkitt lym- phoma in the 2019 NCCN guidelines.2,18 These recom- mendations were driven by the effectiveness of R- EPOCH in individual phase II trials in HIV-associated DLBCL and high-grade lymphoma,19,20 and results from a large meta-analysis that demonstrated greater efficacy for R-EPOCH as compared to R-CHOP in HIV-associated lymphoma.21 On the other hand, a phase III trial compar- ing R-CHOP with R-EPOCH in immunocompetent patients with DLBCL found no difference in efficacy.17 Retrospective analysis showed that a high proliferation rate was associated with better prognosis in HIV-associ- ated lymphomas when treated with infusional R- EPOCH but not with R-CHOP, suggesting that tumors with high proliferation rates, such as high-grade lymphoma and a subset of DLBCL may be those most likely to benefit from infusional EPOCH chemotherapy.22 The findings from our study suggest that patients with HIV-associated lymphoma who achieve a complete response after two cycles of EPOCH plus rituximab have excellent outcomes when therapy is limited to four cycles, thereby sparing toxicity associated with longer treatment durations.
Dunleavy et al. reported a phase II study including 33 patients with HIV-associated DLBCL who received three to six cycles of dose-dense rituximab (SC-EPOCH-RR), of whom 79% received three cycles of therapy based on a risk-adapted approach of treating for one cycle beyond a negative interim PET-CT after cycle 2.23 At the median fol- low-up of 5 years, the progression-free survival rate was 84%, although outcomes were excellent only for those with GCB subtype lymphoma (95% for GCB vs. 44% for non-GCB subtype).23 Only about one-third of patients in our trial had information regarding GCB or non-GCB sub- type, and outcomes were similar irrespective of subtype. Future studies evaluating risk-adapted therapy may need to integrate histological subtyping, be limited to the GCB
N. treated
Male gender, n (%)
Median age, years
Entire population
106
91 (86%) 44
191/mL 33 (31%)
75 (71%)
51 (48%)
56 (52%)
78 (74%) 25 (33%)
15 (14%) 84 (79%) 72 (68%) 25 (24%)
CR ≤4 cycles
24
19 (79%) 43.5
237/mL 5 (21%)
16 (67%)
14 (42%)
10 (58%)
17 (71%) 7 (29%)
5 (21%) 17 (71%) 15 (63%) 3 (13%)
CR 5-6 cycles
40
37 (93%) 44
230.5/mL 12 (30%)
29 (75%)
21 (53%)
19 (47%)
28 (70%) 12 (30%)
3 (8%) 30 (75%) 28 (70%) 10 (25%)
CD4 cell count Median
N (%) of patients with ≤100/ L Concurrent antiretroviral
therapy, n (%)
Concurrent or sequential rituximab, n (%)
Concurrent
Sequential
Local histology, n (%)* Diffuse large cell High grade
Bone marrow involvement
at diagnosis, n (%) Stage III-IV, n (%) Elevated LDH, n (%) ECOGPS2,n(%)
Age-adjusted IPI risk factors, n (%) 0
1 2 3
8(8%) 0 5(12%)
28 (26%) 51 (48%) 19 (18%)
12 (50%) 10 (40%) 2 (10%)
8 (20%) 19 (48%) 8 (20%)
* pathology as determined by local pathologist. CR: complete response; LDH: lactate dehydroge- nase; ECOG PS: Eastern Cooperative Oncology Group Performance Status; IPI: International Prognostic Index.
Table 2. Clinical outcomes for entire population and complete responders strat- ified by number of EPOCH treatment cycles.
Number
Median follow-up
(range)
N. relapsed after CR
EFS rate, % (95% CI) At 1 year
At 2 years
Time to progression, % (95% CI)
At 1 year At 2 years
OS rate, % (95% CI) At 1 year
At 2 years
Entire population
106
30 months
(0-68)
10/64 (16%) (95% CI: 8%- 27%)
71% (61%-79%)
64% (54%-73%)
77% (67%-84%) 73% (63%-81%)
78% (68%-85%)
68% (58%-76%)
CR ≤4 cycles
24
36.5 months
(1-67)
4/24 (17%) (95% CI 5%-37%)
91% (69%-98%)
78% (55%-90%)
91% (69%-98%) 91% (69%-98%)
91% (69%- 98%)
78% (55%-90%)
CR 5-6 cycles
40
40 months
(5-66)
6/40 (15%) (95% CI 6%-30%)
90% (76%-96%)
85% (70%-93%)
92% (78%-97%) 87% (72%-94%)
95% (81%-99%)
90% (75%-96%)
CR: complete response; 95% CI. 95% confidence interval; EFS: event-free survival, OS: overall sur- vival.
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