PS1413 INCIDENCE OF NEGATIVE MINIMAL RESIDUAL DISEASE IN MULTIPLE MYELOMA PATIENTS AFTER AUTOLOGOUS STEM CELL TRANSPLANT
Authors: Afonso C. , Roque A. , Nascimento T. , Sarmento A.B. , Geraldes C. , Paiva A. , Ribeiro L. 
Published: June 2019

Background:

The survival of multiple myeloma (MM) patients (pts) has improved significantly over the last decade. However, MM remains an incurable disease. Minimal residual disease (MRD) is considered a crucial prognostic factor. Previous studies have demonstrated that the presence of MRD at day 100 (d100) following autologous stem cell transplant (ASCT) independently predicts for both progression‐free and overall survival. Several techniques have been developed to detect MRD, including multiparameter flow cytometry (MFC).

Aims:

To estimate the incidence of negative MRD (MRD‐) after induction with bortezomib‐based triplets and ASCT. To investigate the correlation between disease features at diagnosis and response to induction therapy, and MRD negativity.

Methods:

We retrospectively analysed pts diagnosed with MM treated in a single institution with high‐dose therapy and ASCT between July 2016 and November 2018, after receiving induction therapy with VTD or VCD. MRD was assessed by MFC ≈ d100 after ASCT in the bone marrow of all pts, according to recommendations from the EuroFlow consortium. Additional response was assessed according to the IMWG criteria. High‐risk cytogenetic (HRC) abnormalities included del(17p), t(4;14) and t(14;16). Agreement between MRD and other variables was measured by Cohen's kappa test (STATAv.14.0).

Results:

Forty‐nine (49) MM pts were analysed. Among these, 59,2% (n = 29) were male, with a median age at diagnosis of 64 years (40 ‐ 70). Isotype was IgG in 51% (n = 25), IgA in 22,4% (n = 11), kappa Free Light Chain (KFLC) in 18,4% (n = 9) and lambda FLC (LFCL) in 6,1% (n = 3). By the International Staging System (ISS), 26,1% pts (n = 12) were stage III. HRC were detected in 37,5% (9/24). Median time from diagnosis to ASCT was 12,3 months (5,8 – 115). Nine pts (18,4%) received two lines of therapy prior to ASCT. First‐line induction included VCD (n = 43) and VTD (n = 6). Lenalidomide(Len)‐based regimens were the most common second‐line (7/9; 77,8%).

Response prior to ASCT was a complete remission (CR) in 8 pts (16,3%), very good partial remission (VGPR) in 33 pts (67,4%) and partial remission (PR) in 8 pts (16,3%). At d100 after ASCT, thirty pts (61,2%) were MRD‐ (53,3% CR, 43,3% VGPR and 3,3% PR). At this point, in the general population, responses had improved to 40,8% CR (80% MRD‐), 44.9% VGPR (59.1% MRD‐) and 14.3% PR. Kappa coefficient between MRD and ≥VGPR at d100 was 0,32 (fair agreement).

The achievement of ≥VGPR prior to ASCT correlated with MRD negativity (OR 6,46; p = 0.035). MRD‐ status was not influenced by age (OR 1.03; p = 0.534), MM subtype, ISS (OR 1,71; p = 0.215), R‐ISS (OR 0.96; p = 0.952), HRC (OR 0.35; p = 0.414), number of prior lines of therapy (OR 1,33; p = 0.711), first‐line regimen (OR 0.28; p = 0.260) or extramedullary disease at diagnosis (OR 1.31; p = 0.771). At a median follow‐up of 13,5 months after ASCT, 6 pts (12,3%) relapsed: 2 presented MRD+ and 4 MRD‐ at d100 (kappa value 0.03 – poor agreement).

Summary/Conclusion:

In our cohort, nearly 2/3 of pts were MRD‐ after ASCT; there was no significant difference between pts treated with VCD/VTD as first‐line induction. Even pts who required re‐induction with a Len‐based regimen prior to ASCT achieved MRD negativity.

As shown in our study, pts achieving VGPR after ASCT may have MRD‐, highlighting the importance of assessing MRD after ASCT in those pts (not only in CR pts). This phenomenon might be explained by the development of oligoclonal bands after ASCT, not related to the original malignant clone.