Outcomes of Autologous Transplants for Patients with Multiple Myeloma and Concurrent Multiple Plasmacytomas
Authors: Naik Seema , Shaughnessy Paul J. , Zoghi Behyar , Cruz Jose C , Bachier Carlos 
Published: October 2019

Abstract
Introduction: Outcomes of Multiple myeloma (MM) have improved in the recent years with combination of novel agents, autologous transplants followed by maintenance therapies. One of the current challenges is to optimize transplant strategies for MM patients with extramedullary plasmacytomas (EMP).
Patients and Methods: We retrospectively analyzed outcomes of 237 consecutive MM patients (M132:F105) who underwent ASCT at Texas Transplant Institute, between December 2011 and June 2014. The study was approved by Institutional Review Board. The median length of follow-up was 44.8 months (10 - 86.8 months) in all patients. Censoring date was the last clinic visit prior to December 2014.
Results: A total of 237 MM patients were evaluated for presence of plasmacytomas. Patients presented either with multiple intraosseous lytic lesions (MM-IOL) without EMP (n=105; 44%); MM without lytic lesions or EMP in (n=80; 34%) and remaining MM-EMP (n=52; 22%) presented with EMP without multiple lytic lesions. Disease subtype was nonsecretory (5%; n=13), IGA (15%; n=35), IGG (56%; n=133), kappa light chain (16%; n=38) and lambda light chain (8%; n=18) for all 237 patients. (Table 1). Cytogenetics was available in 216 patients (91%) and statistically different among the 3 groups (p=0.05). The sites of EMP included the abdomen, pelvis, chest wall; liver, soft tissue, with sizes ranging from 1.8 cm 10 cm. EMP patients developed recurrent EMP after autologous transplant in 20% (10/52) cases. Fifty percent of patients with recurrent EMP (5/10) died of EMP progression.
A total of 140 (59%) patients received triple drug regimens either CyBorD (n=51; 22%) or VRD (n=89; 38%) prior to transplant. Radiation therapy was given to 42 % (n=22/52) patients with EMP and only 4% patients without EMP (n=8 /185). There was no difference in OS and PFS for patients treated with 2 drugs (VD/RD) compared to 3 drug regimens (CyBorD/VRD) for either OS or PFS. Prior solitary plasmacytoma were seen more frequently in 19% patients (n=10/52) who had EMP manifestations prior to transplant. Prior MGUS /smoldering myelomas were seen in 13 % MM-IOL patients. Disease characterisitics (p=0.0515), plasma cell percentage (p=0.0119) and disease recurrence (p=<0.0001) were statistically different for OS for all 237 patients. Disease characteristics (p=0.0751) and recurrence (p=<0.0001) were prognostic for PFS. 3 year probability of OS was 82% (95% CI, 64%- 92%), 84.7% (95% CI, 72%- 92%) and 71.6% (95% CI, 53%- 84%) for patients MM without EMP, MM-IOL and MM-EMP, respectively.
Conclusion: Novel therapeutic approaches including proteasome inhibitors and immunomodulatory agents followed by transplant can overcome poor prognosis of MM-EMP patients. Those that do relapse do extremely poorly suggesting need for alternative new therapies.
Table 1. Patient Characteristics Variable All patients MM withoutIOL/EMP MM-IOL MM-EMP (M132:F105) (n=237)(100%) (n=80)(34%) (n=105)(44%) (n=52)(22%) Median age P=0.5038 63 (37-79) 62 (40-76) 63 (37-79) 63 (39-77) MM subtype P=0.9589 IGG subtype 133 (56%) 45(56%) 61(58%) 28(23%) IGG kappa 91 (38%) 31(39%) 42(40%) 18(4%) IGG lambda 42 (18%) 14(18%) 19(18%) 9(17%) IGA Subtype 35 (14.7%) 13(16%) 16(15.2%) 6(12%) Kappa LCD 38 (16%) 14(18%) 16(16%) 8 (15%) Lambda LCD 18 (8%) 4(5%) 8(8%) 6(12%) Nonsecretory 13 (6%) 4(5%) 4(4%) 5(10%) Prior Plasma Cell Disorder* P=0.0001 Smoldering MM* 7 (3%) 3(4%) 4(4%) 0(0%) Plasmacytoma* 13 (6%) 1(1%) 2(2%) 10(19%) MGUS* 26 (11%) 13(16%) 9(9%) 4(8%) Cytogenetics P=0.0586 Normal Cytogenetics 84(34%) 41(51%) 25(26%) 27(54%) Mono 13/13 del 22(13%) 10(13%) 20(19%) 6(12%) 17 del 4(2%) 1(1%) 3(3%) 1(2%) Trisomy 11/t(11:14) 8(3%) 6(8%) 3(3%) 6(12%) T(4:14) 5(2%) 2(2.5%) 4(4%) 2(4%) Hyperdiploidy 22(9%) 6(8%) 11(10%) 2(4%) Prior Treatments P=0.1122 CyBorD 51(22%) 19 (24%) 26(25%) 6(12%) VRD/VTD 89(38%) 27(34%) 43(41%) 18(34%) VD/RD/TD 91(38%) 30(38%) 36(34%) 24(46%) Other 6(2.5%) 3(4%) 0(0%) 3(6%) 3 yr OS (p=0.462) 86.1% (65%-95%) 91.3% (81%-96%) 83.4% (65%-93%) 3 yr PFS (p=0.1302) 82.8% (64%-92%) 84.7% (72%-92%) 71.6% (53%-84%)

Disclosures
Shaughnessy: pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; sonofi/genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.