Page 179 - 2019_02-Haematologica-web

Tandem transplantation for multiple myeloma
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212 87 113 53 30 14 69 33 206/244 84 0 5929 1or2 79 38 ≥3 6833
CMV serostatus
Recipients positive
Recipients negative with Donor positive Recipients and Donor negative
HCT-CI score
KPS scale < 80% Allogeneic HCT conditioning
TBI 200 cGy
TBI 200 cGy + fludarabine 90mg/m2
GvHD prophylaxis
MMF + CSP
MMF+TAC 56 23 MMF + CSP/TAC + SRL 12 5
Median follow up for surviving patients years(range) 8.3 (1.0–18.1)
CMV: cytomegalovirus; CSP: cyclosporine; Dex-Cy: dexamethasone + cyclophosphamide; GvHD: graft-versus-host disease; HCT: hematopoietic cell transplantation; HCT-CI: hematopoietic cell transplantation-comorbidity index; HD-Dex: high-dose dexamethasone; IMiDs: immunomodulatory drugs; KPS: Karnofsky Performance Status; LDH: lactate dehydrogenase; MMF: mycophenolate mofetil; MP: melphalan + prednisone; n: number; PIs: proteasome inhibitors; R-ISS: Revised-International Staging System; SRL: sirolimus; TAC: tacrolimus; TBI: total body irradiation; ULN: upper limit of normal; VAD: vincristine + doxorubicin + dexamethasone.
42/218 19
164 67 80 33
176 72
Table 2. Disease response. Disease status
CR
VGPR
PR
Status at autologous HCT Status at allogeneic HCT Best response after allogeneic HCT n= 244 % n= 244 % n= 244 %
12 5 62 26 111 46
35 14 47 19 42 17 106 42 93 38 49 20
RD/PD 91 39 42 17 42 17
CR: complete remission; HCT: hematopoietic cell transplantation; n: number; PD: progressive disease; PR: partial response; RD: refractory disease;VGPR: very good partial response.
(MMF) (from a minimum of 28 days for sibling recipients to a maximum of 180 days for unrelated donors) and a calcineurin inhibitor (CNI) of either cyclosporine (n=176) or tacrolimus (n=56) for a minimum of 80 days with a subsequent taper to 180 days, as previously described.5 Twelve patients received sirolimus in addi- tion to MMF and CNI at the dose of 2 mg orally once daily from day -3 to day +80 (n=4), day +180 (n=6), and day +365 (n=2).30 Thirty-one patients included in the analysis also received borte- zomib (n=21; either at 1.6 mg/m2 intravenously or 2.6 mg/m2 sub- cutaneously every 14 days for up to 9 months) or lenalidomide (n=10; starting dose of 10 mg per day, range: 5-25 mg per day, on days 1-21 of each 28-day cycle, for 12 cycles of planned treatment) as maintenance treatment after allogeneic HCT, per protocol, as specified in the Results section.
Chimerism evaluation
Donor chimerism was assessed at days 28, 56, 84, 180 and 365 after allogeneic HCT on peripheral blood CD3+ T lymphocytes and CD33+ myeloid cells, while unfractionated marrow was ana- lyzed only on day +84. This involved FISH analyses in sex-mis- matched pairs and polymerase chain reaction-based studies of polymorphic microsatellite regions in all other patients.31
Disease response assessment
Disease responses were based on the 2016 Uniform Response Criteria developed by the International Multiple Myeloma Working Group32 with some minor modifications. Complete response (CR) required negative immunofixation (IFIX) on the serum and urine, disappearance of any soft tissue plasmacytomas and/or osteolytic bone lesions, <5% plasma cells in bone marrow aspirates, and no evidence of clonal disease on flow cytometry analysis; very good partial response (VGPR) was defined as serum and urine M-protein detectable by IFIX but not on electrophoresis (SPEP) or ≥90% reduction in serum M-protein plus urine M-pro- tein level <100 mg/24 hours (h). Partial response (PR) required ≥75% reduction of serum M-protein and reduction in 24 h urinary M-protein by ≥90% or to <200 mg/24 h and no increases in sizes or numbers of soft tissue plasmacytomas and/or lytic bone lesions; stable or progressive disease (PD) before autologous HCT was defined as chemo-refractory disease, while the achievement of at least a PR as chemotherapy-sensitivity disease. Patients were eval- uated both before autologous HCT and before allogeneic HCT in order to estimate the baseline levels of disease activity before each transplantation, again on days 28, 56, 84 and 180 after allogeneic HCT, and thereafter on a clinical basis. Disease evaluation includ-
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