Introduction:

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) is the standard of care for younger patients with newly diagnosed multiple myeloma (MM). In approximately 15% of MM patients the monoclonal (M) spike consists of k or l light chains only as opposed to heavy + light chains. It remains unclear whether light chain (LC) MM has a different prognosis compared to other monoclonal protein subtypes after an auto-HCT.

Methods:

We retrospectively analyzed 1067 patients with MM who underwent auto-HCT between January 1, 2004 and January 1, 2011 at our institution. We evaluated the outcome of newly diagnosed patients with LCMM and compared it to patients with IgG or IgA MM, who underwent an auto-HCT after induction therapy. Primary endpoints were complete remission (CR), progression-free survival (PFS) and overall survival (OS) from the date of auto-HCT. Kaplan-Meier analysis with the log-rank test was performed for univariate comparison of survival. Cox proportional hazards regression method was used for univariate and multivariate analyses.

Results:

Of 1067 patients who underwent auto-SCT during the period, 223 underwent auto-SCT after relapse, and were excluded. From the remaining 844 who underwent auto-SCT in first remission, we excluded 102 patients (AL amyloidosis 60, POEMS and other plasma cell disorders 10, non-secretory MM 15, IgD 10, IgM 6 and IgE 1) from the analysis. The remaining 742 patients were divided as follows: IgA, 162 patients (22%); IgG, 444 (60%) and LC, 136 (18%). Baseline patient characteristics are described in Table 1. Patients with LCMM were younger and had a higher CR rate to induction. Median follow-up for the entire cohort after auto-HCT was 38 months (range, 0.2-87.0). Post auto-HCT, 28% with IgG/IgA MM and 38% with LCMM achieved a CR (p=0.015). Median PFS was 26.0 months and 27.7 months in IgG/IgA MM and LCMM groups, respectively (p= 0.742). Median OS was not reached and 71.1 months in IgG/IgA MM and LCMM groups, respectively (p= 0.18, Figure 1). Multivariate Cox regression analysis for PFS identified <PR after auto-SCT, non-diploid karyotype, and induction chemotherapy without thalidomide or bortezomib as adverse prognostic factors. Multivariate Cox regression analysis for OS identified presence of hypodiploidy or monosomy 13/del13, higher lactate dehydrogenase pre-transplant, lower hemoglobin pre-transplant, and <PR after auto-HCT as adverse prognostic factors. M protein subtype did not affect PFS (hazard ratio [HR], 1.040; 95% confidence interval [CI], 0.825-1.311; p=0.742) or OS (HR, 1.313; 95% CI, 0.874-1.971; p=0.190).

Conclusions:

Patients with LCMM have a higher CR rate after auto-HCT, but their PFS and OS were similar to patients with IgG/IgA MM.

Table 1.

Patient Characteristics

Variables, No. (%)/median (range)IgG/IgA myeloma
N= 606
Light chain myeloma
N= 136
P
Median age at transplant, (y) 59 (31-80) 56 (32-78) .004 
Age >65 years 138 (23) 23 (17) .134 
Male 357 (59) 74 (54) .337 
Ethnicity .731 
Caucasian 399 (66) 94 (69) 
African American 99 (16) 22 (16) 
Mixed 87 (14) 18 (13) 
Asian 16 (3) 2 (2) 
Cytogenetic abnormalities at diagnosis by conventional cytogenetics 
Diploid 180 (30) 36 (27) .159 
Hyperdiploid 93 (15) 9 (7) .008 
Hypodiploid 27 (5) 11 (8) .082 
t(11;14) 4 (1) 3 (2) .092 
Monosomy 13 / del 13 44 (7) 9 (7) .789 
Other high-risk abnormalities 2 (0) 1 (1) .456 
Induction chemotherapy 
Bortezomib or IMiD-based 507 (84) 123 (90) .046 
Pre-transplant evaluation 
Bone marrow plasma cell, (%) 2 (0-71) 2 (0-50) .136 
Bone marrow plasma cell >10% 90 (15) 18 (13) .735 
Hemoglobin, (g/dL) 11.3 (4.4-16.0) 10.8 (6.8-15.3) .025 
Lactate dehydrogenase, (IL/L) 526 (221-5062) 526 (239-2748) .522 
Calcium, (mg/dL) 9.0 (7.6-10.4) 9.0 (7.5-11.0) .055 
Creatinine, (mg/dL) 0.9 (0.4-12.5) 0.9 (0.5-9.8) .017 
Beta-2 microglobulin (mg/dL) 2.4 (1.1-40.0) 2.8 (1.2-33.8) .001 
Time from diagnosis to auto-HCT (month) 8.0 (1.9-174.4) 6.8 (2.4-44.6) .001 
Pre-transplant disease status .004 
≥ CR 24 (4) 15 (11) 
VGPR/PR 545 (90) 109 (80) 
SD/PD 37 (6) 12 (9) 
Conditioning regimen .008 
Melphalan alone 508 (84) 126 (93) 
Melphalan-based regimen 98 (16) 10 (7) 
Final response after transplant .080 
≥ CR 168 (28) 52 (38) 
VGPR/PR 353 (58) 70 (52) 
SD/PD 81 (13) 14 (10) 
Variables, No. (%)/median (range)IgG/IgA myeloma
N= 606
Light chain myeloma
N= 136
P
Median age at transplant, (y) 59 (31-80) 56 (32-78) .004 
Age >65 years 138 (23) 23 (17) .134 
Male 357 (59) 74 (54) .337 
Ethnicity .731 
Caucasian 399 (66) 94 (69) 
African American 99 (16) 22 (16) 
Mixed 87 (14) 18 (13) 
Asian 16 (3) 2 (2) 
Cytogenetic abnormalities at diagnosis by conventional cytogenetics 
Diploid 180 (30) 36 (27) .159 
Hyperdiploid 93 (15) 9 (7) .008 
Hypodiploid 27 (5) 11 (8) .082 
t(11;14) 4 (1) 3 (2) .092 
Monosomy 13 / del 13 44 (7) 9 (7) .789 
Other high-risk abnormalities 2 (0) 1 (1) .456 
Induction chemotherapy 
Bortezomib or IMiD-based 507 (84) 123 (90) .046 
Pre-transplant evaluation 
Bone marrow plasma cell, (%) 2 (0-71) 2 (0-50) .136 
Bone marrow plasma cell >10% 90 (15) 18 (13) .735 
Hemoglobin, (g/dL) 11.3 (4.4-16.0) 10.8 (6.8-15.3) .025 
Lactate dehydrogenase, (IL/L) 526 (221-5062) 526 (239-2748) .522 
Calcium, (mg/dL) 9.0 (7.6-10.4) 9.0 (7.5-11.0) .055 
Creatinine, (mg/dL) 0.9 (0.4-12.5) 0.9 (0.5-9.8) .017 
Beta-2 microglobulin (mg/dL) 2.4 (1.1-40.0) 2.8 (1.2-33.8) .001 
Time from diagnosis to auto-HCT (month) 8.0 (1.9-174.4) 6.8 (2.4-44.6) .001 
Pre-transplant disease status .004 
≥ CR 24 (4) 15 (11) 
VGPR/PR 545 (90) 109 (80) 
SD/PD 37 (6) 12 (9) 
Conditioning regimen .008 
Melphalan alone 508 (84) 126 (93) 
Melphalan-based regimen 98 (16) 10 (7) 
Final response after transplant .080 
≥ CR 168 (28) 52 (38) 
VGPR/PR 353 (58) 70 (52) 
SD/PD 81 (13) 14 (10) 

Figure 1.

a) Progression-free survival, b) Overall survival in patients with light chain myeloma compared to those with IgG/IgA myeloma

Figure 1.

a) Progression-free survival, b) Overall survival in patients with light chain myeloma compared to those with IgG/IgA myeloma

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Disclosures

Shah:Celgene: Consultancy, Research Funding. Thomas:Novartis, Celgene, Acerta Pharmaceuticals, Idera Pharmaceuticals: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.

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