denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Program: Oral and Poster Abstracts
Session: 731. Clinical Autologous Transplantation: Results: Poster I
Introduction: Mantle cell lymphoma (MCL) often follows an aggressive course and remains incurable with standard therapies. First-line chemotherapy followed by consolidation with high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) has become a standard of care in eligible patients (pts). As relapse remains the main cause of treatment failure, strategies such as intensifying induction therapy with high-dose cytarabine or adding rituximab maintenance (RM) have been tested to reduce the relapse rate (RR) post-ASCT. We evaluated the effect of the addition of cytarabine and RM on the outcome of pts undergoing ASCT.
Methods: We conducted a retrospective analysis of consecutive MCL pts who underwent ASCT after first-line chemotherapy at the Princess Margaret Cancer Centre between 2000-2013. Pts received induction with CHOP, RCHOP, or RCHOP alternating with RDHAP (RCHOP/RDHAP), followed by HDT with or without total body irradiation (TBI). All pts had a documented response to induction using Cheson 1999 criteria. After ASCT, pts received maintenance with single-agent rituximab 375 mg/m2 or were simply observed.
Results: 98 MCL pts were treated: median age was 56 years (36-66), 15 pts (15%) had blastoid or pleomorphic subtype, 85 pts (87%) had stage IV disease. MIPI was high risk in 18 pts (19%). Induction therapy: CHOP 14 pts (14%), RCHOP 57 (58%), and RCHOP/RDHAP 27 (28%). After induction CR was obtained in 44%, PR in 56% pts. CR rates were: CHOP 7 (50%), RCHOP 25 (44%), RCHOP/RDHAP 12 (44%) (P=ns). 89% pts had collected > 5*106 CD34/kg after RCHOP, and 78% after RCHOP/RDHAP (P=ns). Overall 66/98 pts (67%) had > 5*106 CD34/kg collected with 1 apheresis (Table 1). HDT was melphalan+etoposide for 63% pts, cytarabine+melphalan for 31% pts; 77 (79%) also received TBI. Median time from diagnosis to ASCT was 7.5 months (2.5, 33.4). Post-ASCT responses: CR 92 pts (94%), PR 4 (4%), 2 (2%) PD. Median time to ANC ≥0.5 were 10 days (CHOP), 11 days (RCHOP), and 11 days (RCHOP/RDHAP), while median days to PLT≥20 were 9 (CHOP), 11.5 (RCHOP), and 13 (RCHOP/RDHAP). Post-ASCT, 31% of pts had normal blood counts at 3 months which improved to 52% at 1 year post-ASCT. Maintenance data were available for 95/98 pts. RM was given to 72 pts (74%). Median follow-up from date of transplant for the entire cohort was 3.22 years (range 0.7 – 14.1). The 2-year and 5-year PFS were 85.8% (76.7-91.5) and 52.2% (37.7-64.7), respectively. 32 pts relapsed after ASCT (32.65%). Relapse occurred in 3 (11%) pts after RCHOP/RDHAP, 19 (33%) after RCHOP, and 10 (71%) after CHOP. Median time to relapse was 9 years (95%CI: 4.7-NR). 2-year and 5-year RR were 14.54% and 41.65%, respectively. Median OS was 9.15 years (95%CI: 7.3-NR), 2-year OS was 88.8% (80.2-93.8), and 5-year OS was 74.9% (61.7-84.2%). For patients observed without treatment post-ASCT, median PFS was 2.87 years (1.22-4.63) and median OS 5.19 years (1.66-NR), while for those receiving RM, PFS was 9.06 years (4.97-NR, p<0.001) and median OS has not yet been reached (7.30- NR, p=0.009).
Conclusions: Response rate and PFS were similar between different induction regimens. The outcomes of responding pts following ASCT appear superior to previous strategies. Our patients enjoyed a very long PFS and median OS is surprisingly long as well. Within the limits of a retrospective study, our data support the use of rituximab maintenance, showing a significant benefit in both PFS and OS.
Table 1: ASCT data |
|
|||
Stem cell collection |
CHOP
|
RCHOP
|
RCHOP/RDHAP
|
P value |
Pts collecting > 2x106/Kg CD34+ cells in 1 day |
4/14 (29%) |
44/57 (77%) |
17/27 (67%) |
0.002 |
Pts collecting 2-5 x106/Kg CD34+ cells |
N/A |
6/57 (11%) |
6/27 (22%) |
|
Pts collecting >5 x106/Kg CD34+ cells |
N/A |
51/57 (89%) |
21/27 (78%) |
0.153 |
|
|
|
|
|
Engraftment median (range) |
|
|
|
|
Days to ANC ≥ 0.5 |
10 (9,11) |
11 (9, 12) |
11 (9, 12) |
|
Pts with ANC ≥ 0.5 ≤ 11 days |
13/13 (100%) |
45/52 (87%) |
21/25 (84%) |
0.33 |
Days to PLT ≥ 20 |
9 (7, 15) |
11.5 (9, 17) |
13 (9, 26) |
|
Pts with PLT ≥ 20 ≤ 12 days |
12/13 (92%) |
37/52 (71%) |
8/25 (32%)
|
0.0001* |
Days from ASCT to discharge |
13 (11,26) |
14 (11,30) |
13 (11,23) |
|
PTs requiring RBC Transfusions |
11 (79%) |
43 (75%) |
22 (81%) |
0.821 |
Number of RBC Transfusions |
2 (0, 4) |
2 (0, 7) |
3(0, 6) |
|
Pts requiring PLT Transfusions |
12 (86%) |
52 (93%) |
25 (93%) |
0.759 |
Number of PLT Transfusions |
1 (0, 4) |
2 (1, 9) |
3 (1, 5) |
|
* comparison CHOP Vs R-CHOP: not significant, p=0.113
Legend. ASCT: autologous stem cell transplant; Pts: patients; ANC: absolute neutrophils count;
PLTs: platelets; RBC: red blood cells.
Disclosures: Kuruvilla: Hoffmann LaRoche: Consultancy , Honoraria , Research Funding ; Seattle Genetics: Consultancy , Honoraria ; Gilead: Consultancy ; Janssen: Consultancy , Honoraria ; Merck: Honoraria ; Bristol-Myers Squibb: Honoraria ; Lundbeck: Honoraria ; Karyopharm: Honoraria .
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