Page 167 - 2019_02-Haematologica-web

Outcome in MM after allo-SCT
Table 1. Patients’ characteristics.
Distribution according to therapeutical concept
Distribution according to time point of allo-SCT
All n=109
First-line treatment n=46
Salvage situation n=63
2000 - 2004 n=19
2005 - 2009 2010 - 2016 n=37 n=53
Medianage[years](range) 56(30-70) 53(30-67) 58(42-70) 55(39-67) 57(43-70) 55(30-69)
Medianbodyweight[kg](range) 75(40-103) 72(40-99) 78(42-103) 71(40-95) 73(51-98) 78(42-103) Sexmale/femalen(%) 56(51)/53(49) 24(52)/22(48) 32(51)/31(49) 9(47)/10(53) 20(54)/17(46) 27(51)/26(49) MM/plasmacellleukemian(%) 106(97)/3(3) 44(96)/2(4) 62(98)/1(2) 18(95)/1(5) 36(97)/1(3) 52(98)/1(2)
Treatment within DSMM-trial yes/non(%) First-linetreatment/
salvage situation n (%) Stage according to ISS n (%)
I/II
III β2-MG ≥ 5.5mg/L n.e.
Cytogenetics n (%)
Summary of all subgroups Standard risk
High risk
Poor risk
Ultra high risk Del13-analysis only **
n.e.
MM: multiple myeloma; DSMM: German Myeloma Study Group; ISS: International Staging System; n.e.: not evaluated, β2-MG: beta-2 microglobulin. Cytogenetics: high risk: non- hyperdiploid karyotype, t(4;14), t(14;16), t(14;20), del 17p; poor risk: gain 1q, del 1p; ultra-high risk: ≥ 3 chromosomal aberrations. *% of patients with complete cytogenetic analy- sis. **Implemented into International Myeloma Working Group protocols.
40 (37) / 69 (63) 34 (74) / 12 (26) 7 (11) / 56 (89) 5 (26) / 14 (74) 19 (51) / 18 (49) 16 (30) / 37 (70)
46(42)/63(58) 46(100)/0(0) 0(0)/63(100) 10(53)/9(47) 17(46)/20(54) 18(34)/35(66)
62(57) 26(57) 36(57) 7(37) 26(70) 29(55) 40 (37) 20 (43) 20 (32) 12 (63) 8 (22) 20 (38) 7(6) 0(0) 7(11) 0(0) 3(8) 4(7)
57 (52) 20 (35*) 25 (44*) 8 (14*) 4 (7*) 33 (30)
20 (44) 8 (40*) 9 (45*) 1 (5*) 2 (10*) 18 (39)
37 (59) 12 (33*) 16 (43*) 7 (19*) | 2 (5*) 15 (24)
2 (11) 1 (50*) 1 (50*) 0 (0*) 0 (0*) 6 (31)
10 (27) 2 (20*) 6 (60*) 0 (0*
2 (20*)
24 (65)
45 (85) 17 (38*) 18 (40*) 8 (18*) 2 (4*)
3 (6)
19(18) 8(17) 11(17) 11(58) 3(8) 5(9)
in patients with MM, over the last decades the number of transplantations has increased.5 However, there are few clear treatment guidelines, as it is often performed on an individual basis in relapsed/refractory MM and not in the context of clinical studies.
Despite a high remission rate of up to 50% in retrospec- tive analyses, early approaches in the 1980s and 1990s with high-dose myeloablative conditioning regimens were limited to younger patients with relapsed/refractory disease due to the high therapy-related toxicity, with NRM rates of 40-60%.6 NRM could be reduced through improved supportive care and a more rigorous patient selection, but long-term survival was only achieved in 10- 25% of patients.6
Consequently, a tandem approach was developed to sep- arate myeloablation with maximal tumor cytoreduction achieved through high-dose chemotherapy followed by autologous (auto)-SCT, and allo-SCT with a less myelosup- pressive but highly immunosuppressive regimen to reduce treatment-related organ toxicities but allow sufficient engraftment and GvM effect.7
In the era before the introduction of immunomodulatory drugs (IMID) and proteasome inhibitors (PI), several clinical trials were performed to analyze the combination of auto- and subsequent reduced-intensity conditioning (RIC) allo- SCT in the first-line treatment. Only two large trials with long-term follow up reached significance. In both studies, PFS and OS were superior with auto-allo-SCT compared to
tandem auto-SCT.8,9 The results suggested that high-risk cytogenetics may be overcome by allo-SCT. None of the trials showed inferiority of the auto-allo-SCT approach compared to single or double auto-SCT-study arms.10-14
Similarly, most retrospective studies comparing salvage allo- with a second auto-SCT in patients with relapsed MM after auto-SCT showed an improvement in PFS or a lower relapse rate after allo-SCT, but no benefit regarding OS, mostly due to high NRM.15-18 However, in one study, after a very long follow up, PFS and OS were both superior with the allo-SCT approach.19 There have been no prospective studies comparing allo- with auto-SCT in salvage situa- tions.
Encouraging results were obtained with the combination of allo-SCT and immunomodulatory therapeutic approach- es. The induction of a sustained anti-neoplastic effect by donor lymphocyte infusions (DLI) could be demonstrated in patients who had relapsed after allo-SCT,3,20 also in com- bination with IMID and PI.21
Several clinical trials are currently ongoing that may help to define the role of allo-SCT, particularly in the context of new immunomodulatory approaches, emphasizing the importance of this therapeutic concept. In the light of this background, here we analyzed a substantial number of MM patients who had received RIC allo-SCT at our University Medical Center between 2000 and 2016 with regard to treatment response, survival, adverse events, and quality of life (QoL).
haematologica | 2019; 104(2)
371