Abstract
BACKGROUND: MCL remains incurable with cytotoxic therapy, but may be susceptible to immune-based modalities. Since the availability of NMT(1997) and rituximab(1999), we have employed the following risk-adapted strategy: patients (pts) in first remission after one chemotherapy (REM1) were offered autologous SCT (ASCT) with high-dose rituximab (R), and pts beyond REM1 were offered NMT if a donor was available, and ASCT+R if not. In order to assess the success of this strategy, we analyzed the results of 17 years of MCL transplantation at our center, including ASCT pts transplanted without R as historical controls.
METHODS: 52 pts in REM1 (ASCT1) and 36 pts beyond REM1 (ASCT2) received ASCT with (43%) or without (57%) R, and 35 pts beyond REM1 received NMT with fludarabine, cyclophosphamide & R. ASCT1, ASCT2 and NMT pts were balanced for age, Ann-Arbor stage, B-symptoms, LDH and B2m, but NMT pts were more heavily pretreated (p=0.01) and were further from initial diagnosis (p=0.02) than ASCT2 pts.
RESULTS {ASCT}: 96% & 91% of ASCT1 & ASCT2 pts were in CR following transplantation. Chemoresistance was an important determinant of ASCT outcome, with ASCT1 pts experiencing superior median PFS (42 v 27 months, p=0.009) and OS (94 v 52 months p=0.01) than ASCT2. B-symptoms and B2m≥3.0mg/L adversely affected OS in both ASCT groups. There was a trend to improved PFS for the 20 ASCT1 pts who received R, with no events in 10 pts followed between 24 to 94 months, compared with a continuous pattern of progression in non-R pts (p=0.06). {NMT}: 94% of pts were in CR after transplantation, and the 42 month current-PFS was 57%. In contrast to the ASCT pts, OS following NMT was not affected by high B2m, although B-symptoms remained significant (p=0.03). Despite all pts being transplanted beyond REM1, a plateau in survival was evident with no deaths occurring among 11 pts followed between 46 to 98 months (figure). Actuarial non-relapse mortality (NRM) at 90 days, 12 months and 2 years were 0%, 13% and 20% respectively. Neither the stem cell source (related 69% v unrelated 31%) nor a history of previous autologous transplantation (n=6) had a significant impact on NMT outcome (p>0.30 for PFS, OS and NRM).
CONCLUSIONS: These results suggest that ASCT is most effective in pts transplanted in REM1, in whom the addition of R may have improved PFS. NMT is effective in overcoming the adverse impact of prior chemotherapy and high B2m, and remains the modality of choice for pts beyond first remission.
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