Page 174 - Haematologica Vol. 109 - July 2024

ARTICLE - ASCT in refractory or early relapsed DLBCL
A.M. Tun et al.
teristics of patients at initial diagnosis are summarized in Online Supplementary Table S1. Clinical characteristics at relapse are described in Table 1. Of the total 230 patients, 157 (68%) had refractory disease or relapsed within 6 months of completing frontline therapy and 73 (32%) had a relapse between 6 to 12 months after frontline therapy. The median age at relapse/ST was 60 years (range, 19-78), and 107 (47%) patients were aged >60 years. The Eastern Cooperative Oncology Group performance status was ≤1 in 181 (97%) patients. Fifty-six patients (39%) had an elevated level of lactate dehydrogenase, 21 (12%) had involvement of more than one extranodal site, and 109 (61%) had ad- vanced stage disease. Treatment patterns and responses to therapy are presented in Online Supplementary Table S2. First-line ST consisted of platinum or high-dose cy- tarabine-containing chemotherapy in 201 (87%) cases. A median of one line (range, 1-3) of ST was required. The number of lines of ST was one in 178 (77%) and more than one in 52 (23%) patients. Response before ASCT was CR in 106 (46%) and PR in 124 (54%) patients. The median age at ASCT was 60 years (range, 19-78). A BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regi- men was used in 213 (93%) patients. Following ASCT, 123 (56%) patients achieved CR, and 18 (8%) patients received post-ASCT consolidative radiation therapy.
Outcomes following autologous stem cell transplantation
The median follow-up after ASCT was 89.4 months (95% confidence interval [95% CI]: 73.5-99.2), and post-ASCT outcomes at 12 months, 24 months, and 60 months are summarized in Online Supplementary Table S3. The median PFS and OS after ASCT were 16.1 months (95% CI: 9.3-43.3) and 43.3 months (95% CI: 24.2-75.5), respectively. The 24-month PFS and OS rates were 47% and 57%, respectively (Figure 1A, B). The median DOR in patients who achieved CR or PR after ASCT was 96.4 months (95% CI: 61.6-160.6), with a 24-month DOR rate of 72%. The cumulative incidences of post-ASCT relapse and non-relapse mortality rate were 43.4% and 3.9%, respectively, at 12 months (Figure 1C). One hundred eighteen patients had a relapse (see Online Sup- plementary Table S4 for their subsequent management), with a median post-relapse OS of 6.0 months (95% CI: 3.8-8.3) (Online Supplementary Figure S2), and 136 died during the follow-up (see Online Supplementary Table S5 for causes of death). Lymphoma was the primary cause of death after ASCT, with a 12-month estimated death rate of 28.5% due to lymphoma, 2.1% due to therapies, 1.3% due to other causes, and 0.9% of unknown causes (Figure 1D).
Outcomes according to clinicopathological characteristics
No statistically significant differences in PFS and OS were seen based on age at relapse, sex, Eastern Cooperative Oncology Group performance status, serum lactate de-
hydrogenase level, extranodal site involvement, and stage at relapse (Table 2). Time to first relapse/refractory status (relapse between 6-12 months vs. refractory or relapse <6 months after frontline therapy) was not associated with a significant difference in PFS (median PFS 29.6 vs. 10.1 months; P=0.47) (Figure 2A, Table 2), but there was a trend for improvement in OS (median OS 88.5 vs. 28.0 months; P=0.07) (Figure 2B, Table 2). Patients who required one line of ST, compared to those who required more than one line of ST, had significantly better PFS (median PFS 37.9 vs. 3.9 months; P=0.0005) (Figure 2C, Table 2) and OS (median OS 68.3 vs. 12.0 months; P=0.0005) (Figure 2D, Table 2). In addition, patients who achieved a CR pri- or to ASCT, compared to those who achieved a PR, had significantly better PFS (median PFS 71.1 vs. 6.3 months; P<0.0001) (Figure 3A, Table 2) and OS (median OS 110.3 vs. 18.9 months; P<0.0001) (Figure 3B, Table 2). Patients who achieved CR after one line of ST had the most favorable PFS and OS, with median PFS of 88.5 vs. 9.1 vs. 12.0 vs. 3.2 months (P<0.0001) and median OS of 117.2 vs. 28.8 vs. 32.5 vs. 7.1 months (P<0.0001) in cases with CR after one line of ST vs. PR after one line of ST vs. CR after more than one line of ST vs. PR after more than one line of ST (Figure 3C,
Table 1. Characteristics of patients with relapsed or refractory diffuse large B-cell lymphoma at relapse/salvage therapy.
N=230 %
Time to relapse (from completion of frontline therapy)
Refractory/relapse <6 months† 157 68
Relapse between 6 and 12 months 73 32
Age at relapse in years
≤60 123 53
>60 107 47
Age at ASCT in years
≤60 117 51
>60 113 49
ECOG PS scale
≤1 181 97
>1 53
Missing 44 -
Lactate dehydrogenase
Normal 87 61
Elevated 56 39
Missing 87 -
Extranodal sites
≤1 161 88
>1 21 12
Missing 48 -
Ann Arbor stage
I-II 70 39
III-IV 109 61
Missing 51 -
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†Primary refractory diffuse large B-cell lymphoma (N=106) and relapsed in <6 months (N=51). ASCT: autologous stem cell transplant; ECOG PS: Eastern Cooperative Oncology Group performance status.