Comparable Outcomes in Secretory (SM) Versus Non-Secretory (NSM) Multiple Myeloma (MM) with Autologous Hematopoietic Stem Cell Transplantation (AuHCT).
Authors: Kumar Shaji , Pérez Waleska S. , Zhang Mei-Jie , Bredeson Christopher N. , Lacy Martha Q. , Milone Gustavo , Reece Donna , Vesole David H. , Hari Parameswaran 
Published: October 2019

BACKGROUND: Non-secretory myeloma (NSM), where immunofixation fails to detect a monoclonal protein in serum and/or urine, accounts for <5% of cases of multiple myeloma (MM). The outcome of patients with NSM versus SM undergoing AuHCT has not been evaluated in clinical trials and patients with NSM are often excluded from clinical trials of MM therapy.

METHODS: We compared the probabilities of treatment-related mortality (TRM), disease progression, progression-free survival (PFS) and overall survival (OS) after AuHCT for patients with NSM versus SM transplant between 1989 and 2003, reported to the CIBMTR. Immunofixation reports were reviewed to confirm the diagnosis of NSM. 110 patients with NSM were matched to 438 patients with SM using a propensity score (PS) approach. PS were calculated using age at transplant, Durie-Salmon stage at diagnosis, sensitivity to pretransplant therapy, time from diagnosis to transplant and year of transplant. A logistic regression model was fit and a numerical score derived for each case (NSM recipients). Controls (SM) were matched in random order to cases with similar PS. Multivariate Cox proportional hazards regression models were stratified on matched pairs. Recipients who had a planned second transplant (whether they received their 2nd transplant or not) were excluded.

RESULTS: The two groups were similar with respect to disease characteristics at diagnosis (bone marrow plasmacytosis, ISS, renal function) and at transplant (performance status,β2-microglobulin, prior therapy and presence of bone disease). Patients with SM were more anemic and had lower serum albumin levels at diagnosis, while those with NSM were more likely to have preceding plasmacytoma and radiation therapy, presumably to the plasmacytoma. 5-year outcomes, with a median follow-up of 66 months (range, 1 – 177) were as follows:

Outcome, Probability (95% CI) NSM SM P-value TRM, % 8 (3 – 14) 7 (5 – 10) 0.86 Disease progression, % 65 (55 – 75) 72 (67 – 76) 0.21 PFS, % 27 (18 – 37) 20 (16 – 25) 0.20 OS, % 51 (40 – 67) 43 (38 – 48) 0.22

In multivariate analysis, based on a Cox model stratified on matched pairs and adjusted for covariates not considered in the propensity score, we found no difference in outcome between the NSM and SM groups. The causes of death were similar between the two groups with disease progression accounting for 75% of deaths.

CONCLUSION: In this large cohort of patients undergoing AuHCT, we found no difference in the outcome of patients with NSM compared to those with SM. With increasing use of the free light chain assay, the majority of patients with NSM are expected to have detectable light chain abnormalities thus making them oligosecretory rather than truly non-secretory. This group of patients is generally underrepresented in prospective clinical trials of MM. This study establishes that the post transplant outcomes of this subset of patients are not different and suggests that they should not be excluded from clinical trials.