Page 117 - Haematologica July

Dismal outcome of refractory/relapsed PTCL
but for whom the clinician specified in the planned treat- ment schedule that HCT was going to be given as consol- idation, and who did not receive additional salvage thera- pies, were also considered to have received HCT as part of first-line therapy. Of those who received HCT, 41 patients were in first remission, 12 (3%) had refractory and 22 (11%) had relapsed disease.
Details of salvage treatments are shown in Table 2. Overall, 99 patients (16%) received HCT as part of salvage treatment. Of those with refractory disease, 62% did not achieve at least a PR with salvage therapy and were there- fore not eligible to undergo transplantation. Twenty-nine percent responded well to salvage therapy but were not considered candidates for transplantation. In the relapsed group, likewise, most of the patients (71%) did not under- go transplantation. Data on the reason why patients eligi- ble for transplant were not referred to HCT consolidation was not collected; the choice as to whether the patient should go forward for transplant was at the physician’s discretion.
Survival after relapse
After a median follow up of 38 months (range 1-96 months) from documentation of refractory/relapsed dis- ease, 440 (70%) patients had died. The median survival after relapse (SAR) was 5.8 months (95%CI: 4.9-7.2 months) and 3-year SAR was 23% (95%CI: 19-27) (Figure 2A). Median SAR for refractory and relapsed patients were 5 and 11 months, respectively, and 3-year SAR rates were similar for both groups at 21% (95%CI: 17-25) and 28% (95%CI: 21-35), respectively (Figure 2B). Univariate analysis showed that in the first 24 months refractory patients had a poorer outcome with respect to relapsed patients [Hazard Ratio (HR) HR 1.50, 95%CI: 1.12-1.86; P<0.001], while after 24 months their outcome became similar to that of the relapsed group (HR 0.75, 95%CI: 0.34-1.64; P=0.470). (Figure 2B). No difference was found in outcomes for refractory/relapsed patients with respect to PTCL subtype, with the excep- tion of ALCL ALK+ (Figure 3).
As expected, patients responding to salvage therapy who proceeded to HCT had a better outcome compared to patients with no response (and therefore, ineligible for HCT) and to patients in CR/PR not eligible for HCT (for any reason), with 3-year survival rates of 48%, 7% and 30%, respectively. Similarly, patients proceeding to HCT had significantly better outcome than patients who were eligible but did not undergo HCT for any reason (3-year SAR 48% and 27%).Overall, patients who received HCT had a better outcome with respect to the subset of patients who did not (3-year SAR 48% and 18%, respec- tively) (P<0.001) (Table 3 and Figure 4).
In a univariate Cox regression analysis, refractory disease was associated with a higher risk of death compared to relapsed patients (HR 1.43, 95%CI: 1.16-1.76; P=0.001), whereas late relapse compared to early relapse (HR 0.57, 95%CI: 0.41-0.79; P=0.001) and salvage therapy with HCT compared to no HCT (HR 0.36, 95%CI: 0.26-0.48; P<0.001) were associated with a longer SAR (Table 3).
Table 3. Univariate Cox regression analysis for SAR.
Status
Relapse
Refractory
Early relapse (≤ 12 months) Late relapse (> 12 months) Not eligible to HCT <PR Not eligible to HCT (CR/PR) Eligible HCT (CR/PR)
HCT
No HCT at salvage
HCT at salvage
3-year SAR%(95%CI)
28 (21-35) 21 (17-25) 23 (16-32) 34 (21-48) 7 (3-11) 30 (21-38) 27 (19-36) 48 (37-58) 18 (14-22) 48 (37-58)
HR (95%CI)
1.00
1.43 (1.16-1.76) 1.00
0.57 (0.41-0.79) 1.00
0.43 (0.34-0.55) 0.45 (0.35-0.58) 0.22 (0.16-0.30) 1.00
0.36 (0.26-0.48)
CR: complete remission; PR: partial remission; SAR: survival after relapse; HCT: hematopoietic cell transplantation; HR: Hazard Ratio; CI: Confidence Interval
Figure 3. Outcomes for refractory/relapsed patients depending on histological subtypes. PTCL-NOS: peripheral T-cell lym- phoma not otherwise specified; AITL:
haematologica | 2018; 103(7)
angioimmunoblastic T-cell phoma; ALCL (-): anaplastic large cell lymphoma, anaplastic lymphoma kinase negative; ALCL (+): anaplastic large cell lymphoma, anaplastic lym- phoma kinase positive; NKTCL: extra- nodal NK/T-cell lymphoma.
lym-
1195