PF630 MINIMAL RESIDUAL DISEASE MONITORING AND DEPTH OF RESPONSE IN MULTIPLE MYELOMA
Authors: Martinez‐Lopez J. , Wong S. , Shah N. , Bahri N. , Martin T. , Wolf J. 
Published: June 2019

Background:

Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). The majority of data comes from retrospective or subset analyses of patients enrolled in clinical trials.

Aims:

We present here a single institution's experience assessing MRD in MM patients receiving frontline therapy as well as those receiving therapy for relapsed disease. We describe the impact of depth of response, duration of response, and direction of response, on prognosis.

Methods:

181 multiple myeloma patients treated at The University of California, San Francisco (UCSF) from 2008 to 2016 were included. 126 were newly diagnosed patients versus 55 in second line or later. Patients received anti‐MM therapy per provider preference with the aim of obtaining maximal response by International Myeloma Working Group (IMWG) criteria and MRD was assessed in those achieving VGPR or better. MRD assessment was performed by commercially available next generation sequencing (NGS) of immunoglobulin genes (Adaptive[SN1] biotechnologies, Seattle, WA, USA). The sensitivity of this technique ranged from 10–4‐to‐10–6) and was 10–6in most cases. Progression Free Survival (PFS) curves were plotted by the Kaplan‐Meier method, and the log‐rank test was used to estimate the statistical significance of differences observed between curves.

Results:

A total of 398 MRD samples were analyzed at various time points during the disease course. MRD data was available at 33 time points for 59 patients, 2 time points for 36 patients and 1 time point for 86. Median follow up was 26 months. Overall, 66 of 181 total patients (36%)achieved MRD negativity (<10–6) on one or multiple assessments.

In the newly diagnosed group, 43 of 126 (34%), patients achieved undetectable MRD on at least one occasion. These patients had a prolonged PFS in comparison with patients who were persistently MRD positive (NR vs 49m[jm1] [SN2], p 0.006) Figure 1.A.

Of the 55 patients who received therapy for relapsed disease, 21 of them achieved MRD negativity (38%) and PFS was also prolonged versus patients who never achieved MRD negative status (53m vs 23m, p = 0.03). Figure 1.B

Also, when we analyzed the effects of depth of response on survival, patients who were MRD negative or who were MRD positive at a very low level (between 10–5and 10–6), had a better prognosis than those with higher disease burdens (>10–5)(p 0.001) Figure 1.C.

Finally, we analyzed the effect of repeated MRD monitoring on PFS. Three categories were identified in newly diagnosed patients: (A) patients with ≥3 MRD‐ samples, (B) patients with continuously declining detectable clones, and (C) patients with a stable number of clones. Groups A and B had a more prolonged PFS than group C (NR vs 31m, p < 0.0001). Figure 2.

Summary/Conclusion:

Conclusion. This study shows that MRD assessment in a real world setting likely has the same predictive power as that seen in clinical trials. MRD dynamics can accurately predict disease evolution and ultimately could drive clinical decision‐ making. MRD is an important predictor of PFS in newly diagnosed and relapsed patients. This study supports the concept of MRD‐driven decision‐making and validates the relevance of MRD in a real‐world MM practice.