Do Cytogenetics Predict Likelihood To Attain Minimal Residual Disease (Mrd) Post Autologous Stem Cell Transplantation (Sct) In Multiple Myeloma (Mm)?

BackgroundDetermination of high risk via genetics plays a significant role in prognosis of disease outcomes in MM. More recently, MRD is emerging as an important prognostic marker and will potentially be used as a surrogate marker in clinical trials. So far, there is limited data on the association between cytogenetics in MM and MRD status. We conducted this study with the hypothesis that cytogenetics in MM would be predictive of MRD status after treatment with high dose chemotherapy and SCT.MethodsPatients who underwent SCT for MM and had MRD data available (tested at day +100 post SCT) were included in the study. Clinical data was obtained via retrospective chart review. Cytogenetic risk (CyR) were classified into high [-17p, t(4;14), t(14;16), 1q gain, t(14;20)] and standard risk [all others including trisomies, t(11;14), t(6;14)], based on the updated mSMART criteria. Disease and SCT related characteristics were compared by MRD status. Comparisons were performed using the chi-squared test for categorical variables and Wilcoxon rank sum test for continuous variables.ResultsA total 144 patients were identified. Median age at diagnosis was 60 years (range, 37-76 years) and at SCT was 62 years (range, 38–78 years). Eighty-eight (61%) were men. CyR was standard risk in 103 (72%) and high risk in 41 (28%) patients. Flow cytometry (FC) was used in 78 (54%) patients while next generation sequencing (NGS) (Clonoseq, Adaptive Biotechnology) in 66 (46%) for MRD detection. In the 66 patients who had both test results available, NGS report was used for this analysis. Amongst these patients, MRD results were discordant in 37 out of 66 (56%) patients (i.e. FC was negative but NGS was positive). This is expected due to difference in sensitivities of the two methods (i.e. 10−4 to 2 × 10−5 for FC and 10−6 for NGS).In the comparison of patients who had high risk vs standard risk cytogenetics, rates of MRD negativity were not statistically significantly different (MRD negative in high risk 37% vs standard risk 32%, p = 0.6) (Figure 1). Several other disease and SCT related characteristics were examined for association with MRD negativity (M-spike levels, presence of extramedullary disease at diagnosis, type of light chain/ heavy chain involvement with MM, prior treatments, use of novel agents, number of lines of induction prior to SCT, disease response at SCT, cell dose and conditioning regimen). Of these, response at SCT was the only variable that was statistically significantly associated with MRD negative results in univariate analysis (Figure 1).ConclusionsIn our study, no association was seen between cytogenetic risk at baseline to achievement of MRD negative status post SCT. This is unexpected and possibly related to the small sample size. This clinical question, however, remains to be of significant clinical utility and should be explored in a larger database. Determination of high risk via genetics plays a significant role in prognosis of disease outcomes in MM. More recently, MRD is emerging as an important prognostic marker and will potentially be used as a surrogate marker in clinical trials. So far, there is limited data on the association between cytogenetics in MM and MRD status. We conducted this study with the hypothesis that cytogenetics in MM would be predictive of MRD status after treatment with high dose chemotherapy and SCT. Patients who underwent SCT for MM and had MRD data available (tested at day +100 post SCT) were included in the study. Clinical data was obtained via retrospective chart review. Cytogenetic risk (CyR) were classified into high [-17p, t(4;14), t(14;16), 1q gain, t(14;20)] and standard risk [all others including trisomies, t(11;14), t(6;14)], based on the updated mSMART criteria. Disease and SCT related characteristics were compared by MRD status. Comparisons were performed using the chi-squared test for categorical variables and Wilcoxon rank sum test for continuous variables. A total 144 patients were identified. Median age at diagnosis was 60 years (range, 37-76 years) and at SCT was 62 years (range, 38–78 years). Eighty-eight (61%) were men. CyR was standard risk in 103 (72%) and high risk in 41 (28%) patients. Flow cytometry (FC) was used in 78 (54%) patients while next generation sequencing (NGS) (Clonoseq, Adaptive Biotechnology) in 66 (46%) for MRD detection. In the 66 patients who had both test results available, NGS report was used for this analysis. Amongst these patients, MRD results were discordant in 37 out of 66 (56%) patients (i.e. FC was negative but NGS was positive). This is expected due to difference in sensitivities of the two methods (i.e. 10−4 to 2 × 10−5 for FC and 10−6 for NGS). In the comparison of patients who had high risk vs standard risk cytogenetics, rates of MRD negativity were not statistically significantly different (MRD negative in high risk 37% vs standard risk 32%, p = 0.6) (Figure 1). Several other disease and SCT related characteristics were examined for association with MRD negativity (M-spike levels, presence of extramedullary disease at diagnosis, type of light chain/ heavy chain involvement with MM, prior treatments, use of novel agents, number of lines of induction prior to SCT, disease response at SCT, cell dose and conditioning regimen). Of these, response at SCT was the only variable that was statistically significantly associated with MRD negative results in univariate analysis (Figure 1). In our study, no association was seen between cytogenetic risk at baseline to achievement of MRD negative status post SCT. This is unexpected and possibly related to the small sample size. This clinical question, however, remains to be of significant clinical utility and should be explored in a larger database.