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Peripheral T-cell lymphoma (PTCL) is a heterogeneous, aggressive non-Hodgkin lymphoma (NHL), accounting for approximately 10% of the Western NHL population and 24%
of the Asian NHL population.
About 60% of PTCLs are so-called "nodular" types, including PTCL non-specific (PTCL-NOS), angioimmunoblastic T-cell lymphoma, and systemic anaplastic large cell lymphoma (sALCL).
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens have been the standard of care for PTCL for decades, and most subtypes have a poor
prognosis.
Several PTCL subtypes express CD30, including sALCL.
In PTCLs that are not sALCL subtypes, CD30 expression is variable; Previous studies have suggested that high CD30 expression may be associated with
poor prognosis for PTCL-NOS.
Patients with PTCL have a high recurrence rate, and usually need to receive high-dose consolidation chemotherapy and autologous hematopoietic stem cell transplantation after first-line chemotherapy; However, due to the lack of randomized controlled studies and the selection bias of existing retrospective studies, there is no consensus on
the use of hematopoietic stem cell transplantation (HSCT) in PTCL.
The randomized, double-blind phase 3 ECHELON-2 study (NCT01777152) showed that first-line vebutuximab combined with cyclophosphamide, doxorubicin, and prednisone (A+CHP) significantly improved progression-free survival (PFS), overall survival (OS), complete response (CR), and overall response rate (ORR) in patients with CD30+ PTCL compared with traditional CHOP regimens, with
。 As first-line therapy improves, the role of HSCT consolidation therapy also needs to be reassessed
.
Based on this, the ECHELON-2 research team conducted a post-hoc exploratory analysis to evaluate the effect of HSCT on the prognostic outcomes of
CD30+ PTCL patients who received first-line A+CHP regimens and achieved CR.
The exploratory study included adults with treatment-naïve CD30+ (≥10%) PTCL, including ALK-ALCL and non-ALCL subtypes
.
Because ALK+ALCL has a good prognosis, HSCT is generally not accepted, so ALK+ALCL patients are excluded
.
Patients are randomized 1:1 to receive either the A+CHP or CHOP regimen for 6 or 8 cycles; The investigators decide whether patients can be treated with consolidation therapy
with HSCT (autologous or allogeneic) or radiotherapy.
The primary endpoint was progression-free survival (PFS).
prognosis in the A+CHP group
114/177 (64%) patients in the A+CHP group achieved CR at the end of treatment, including 76/113 (67%) in the ALK-ALCL subgroup and 38/64 (59%)
in the non-ALCL subgroup.
27/76 (36%) and 11/38 (29%) of ALK-ALCL patients with ALK and non-ALCL received HSCT consolidation therapy
, respectively.
Patients receiving consolidation therapy with HSCT had a lower median age compared to those who did not receive HSCT, either in the ALK-ALCL or non-ALCL subgroups
.
There was no difference
in adverse event rates between patients who received and did not receive HSCT in patients with a clear intention to transplant.
The median follow-up in the A+CHP group was 47.
57 months (95% confidence interval [CI], 41.
89-48.
16).
In the A+CHP group, all patients who received HSCT after achieving CR had a lower
risk of PFS events.
The PFS risk ratio (HR) was 0.
36 (95% CI, 0.
17-0.
77), corresponding to a 64%
reduction in the risk of PFS events in patients receiving HSCT.
In the A+CHP group, the estimated PFS rate at 3 years for patients who received HSCT was 80.
4%, compared with 54.
9%
for those who did not receive it.
Sensitivity analyses excluding ≥ 75-year-old patients (n = 10) showed similar results (HR, 0.
40; 95% CI, 0.
18 to 0.
89).
Similar results were found in the ALK-ALCL and non-ALCL subgroups, as shown in Figure 1
.
Figure 1.
PFS curve of the A+CHP group
Prognostic outcomes in the CHOP group
97/177 (55%) patients in the CHOP group achieved CR at the end of treatment, including 53/105 (50%) in the ALK-ALCL subgroup and 44/72 (61%)
in the non-ALCL subgroup.
In the ALK-ALCL and non-ALCL subgroups, 13/53 (25%) and 16/44 (36%) received HSCT,
respectively.
The median follow-up in the CHOP group was 53.
72 months (95% CI, 47.
54-59.
37).
For the CHOP group, HSCT consolidation therapy showed a trend towards improvement in PFS (HR, 0.
63; 95% CI, 0.
32 to 1.
24), but not as significantly as
in the A+CHP group.
The estimated three-year PFS rate was 67.
2% for patients who received HSCT compared with 54.
1%
for patients who did not receive SCT.
As with the A+CHP group, sensitivity analyses excluding patients ≥aged 75 years (n=9) showed similar results (HR, 0.
73; 95% CI, 0.
36 to 1.
49).
Subgroup analyses of ALK-ALCL and non-ALCL were consistent
with overall PFS results.
This exploratory analysis suggests that patients with CD30+ PTCL should still consider HSCT consolidation therapy even if they receive the superior regimen of A+CHP first-line, whereas patients receiving CHOP regimen do not benefit significantly from SCT consolidation therapy
.
However, this result needs to be supported by larger study data, particularly to determine whether there are good prognostic groups
that benefit from the A+CHP regimen in ALK-ALCL patients with DUSP22 rearrangement and low international prognostic index.
References:
Kerry J.
Savage, Steven M.
Horwitz, Ranjana Advani, et al; Role of stem cell transplant in CD30+ PTCL following frontline brentuximab vedotin plus CHP or CHOP in ECHELON-2.
Blood Adv 2022; 6 （19）: 5550–5555.
doi: https://doi.
org/10.
1182/bloodadvances.
2020003971.
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