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Multiple Myeloma Data

clonoSEQ® in multiple myeloma

Review multiple myeloma data and NCCN guidelines to inform your use of clonoSEQ in routine clinical practice

multiple myeloma data summary

clonoSEQ MRD testing in multiple myeloma: a potential clinical pathway

Based on available evidence, this clinical strategy reflects a potential approach for integrating clonoSEQ MRD testing into the management of multiple myeloma patients.

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Data Spotlight

Collaborators

María-Victoria Mateos, University of Salamanca, Salamanca, Spain

Study objective

Evaluate use of clonoSEQ MRD testing for prognostic evaluation by correlating MRD results to PFS.[1]

Study population

569 relapsed and refractory patients assessed for MRD by clonoSEQ at the time of suspected complete response (CR).[1]

Prognostic value

The clonoSEQ Assay can predict progression-free survival in myeloma patients

MRD negativity (as measured by clonoSEQ at 10-5 threshold) was associated with longer PFS than MRD positivity, regardless of the treatment received

In the ALCYONE (NCT02195479) study of 706 patients with newly diagnosed, transplant-ineligible multiple myeloma, patients received bortezomib, melphalan, and prednisone (VMP) with or without daratumumab (D-VMP). Patients were assessed by clonoSEQ (at a sensitivity level of 10-5) at study screening, and time of CR/sCR, as well as at 12, 18, 24, and 30 months in patients who had achieved a CR/sCR following initiation of induction. After 18 months of follow-up, the proportion of MRD-negative patients in the experimental treatment arm was more than three times higher than in the control group (22.3% versus 6.2%, P<0.001; Figure 1). Additionally, regardless of treatment arm, MRD-negative patients (MRD threshold: 10-5) had longer PFS than MRD-positive patients (Figure 2).[1] The MRD negativity rate data from this study has been incorporated in an FDA-approved product label for the treatment of newly-diagnosed, transplant-ineligible multiple myeloma patients.[2]

Figure 1: Comparison of clonoSEQ MRD negativity rate in the control arm (VMP) versus the experimental arm (D-VMP)

Figure 2: Correlation of clonoSEQ MRD status and PFS

clonoSEQ MRD-negative patients have longer progression-free survival

The POLLUX study assessed 569 relapsed and refractory multiple myeloma patients to determine if the addition of daratumumab to lenalidomide and dexamethasone (Rd) resulted in prolonged progression-free survival. MRD was assessed at three MRD thresholds (10-4 to 10-6) by clonoSEQ at the time of suspected complete response (CR). At three evaluated thresholds, MRD negativity by clonoSEQ was associated with longer PFS relative to MRD positivity (Figure 3, 10-6 threshold shown). Additionally, the rate of MRD negativity at all evaluated thresholds (10-4, 10-5, 10-6) was significantly higher in the experimental treatment arm than in the control arm (by 3-5x). Specifically, at an MRD threshold of 10-5, the rate of MRD negativity was 22.4% in the experimental group (DRd) versus 4.6% in the control group (Rd; P<0.001).[3]

Figure 3: Correlation of clonoSEQ MRD status and PFS

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Real-world case studies
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See how Dr. Saulius Girnius uses MRD to predict outcomes, then visit our Real-world Experience Hub for more video cases.

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Peer-reviewed publications show advantages to using clonoSEQ in multiple myeloma:

MRD assessment by clonoSEQ predicts time to tumor progression (TTP) and overall survival (OS)[4]

Prognostic value

The clonoSEQ Assay has prognostic value in multiple myeloma

MRD by NGS predicts time to tumor progression and overall survival

A study of 133 patients on GEM clinical trials (GEM00, GEM05, and GEM2010) found that MRD assessment by NGS was prognostic for time to progression (TTP; Figure 4) and overall survival (OS; Figure 5).[4]

  • Patients in a CR and MRD negative had longer TTP than patients in a CR who were MRD positive[4]
  • clonoSEQ MRD identified trackable sequences in 121/133 patients (91%)[4]
  • There were 82 concordant MRD results between NGS and flow cytometry. There were 17 discordant MRD cases: 12 were NGS MRD-positive and flow MRD-negative; 5 were NGS MRD-negative and flow MRD-positive

Figure 4 (left): MRD-negativity by NGS was associated with significantly longer TTP
Figure 5 (right): MRD-negativity by NGS was associated with significantly longer OS

Figure 4 (top): MRD-negativity by NGS was associated with significantly longer TTP
Figure 5 (bottom): MRD-negativity by NGS was associated with significantly longer OS


MRD negativity when assessed pre- and post-maintenance at deeper sensitivity correlated with improved outcomes

Sensitivity matters

MRD negativity when assessed pre- and post-maintenance at deeper sensitivity correlated with improved outcomes[5]

Better outcomes for patients who achieve lower levels of disease burden (deeper response) pre-maintenance

When assessing MRD by clonoSEQ, pre-maintenance, patients (N=246) were stratified by level of MRD detected (≥10-4, 10-4 – 10-5, 10-5 – 10-6, <10-6). Patients with the deepest level of MRD negativity (<10-6), had superior PFS compared to clonoSEQ MRD-positive patients with disease >10-6 (P<0.0001, Figure 6).[5]

Figure 6: Correlation of pre-maintenance MRD, assessed by flow cytometry and clonoSEQ, to PFS

Better outcomes for patients who achieve lower levels of disease burden (deeper response) post-maintenance

When assessing MRD by clonoSEQ post-maintenance, patients (N=178) were stratified by level of MRD (≥10-4, 10-4 – 10-5, 10-5 – 10-6, <10-6). Patients with the deepest level of MRD negativity (<10-6) had superior PFS compared to clonoSEQ MRD-positive patients with disease >10-6 (P<0.0001, Figure 7).[5]

Figure 7: Correlation of post-maintenance MRD, assessed by flow cytometry and clonoSEQ, to PFS


clonoSEQ MRD testing identified additional MRD-positive patients who were MRD-negative by flow cytometry in this study

Additional patients captured with clonoSEQ MRD detection

clonoSEQ MRD testing identified additional MRD-positive patients who were MRD-negative by flow cytometry in this study[5]

Additional 84 MRD-positive patients captured pre-maintenance

In a study evaluating MRD in 475 patients, 322 patients had no detectable disease by flow cytometry, of which 163 patients were assessed by clonoSEQ. Of the clonoSEQ-assessed patients, 84 were identified as MRD-positive. These 84 patients had worse PFS compared to patients who had no detectable MRD by flow and were NGS MRD-negative (P=0.0002, Figure 8).[5]

Figure 8: Pre-maintenance assessment of MRD by NGS in patients who were MRD-negative by flow cytometry

Additional 42 MRD-positive patients captured post-maintenance

Post-maintenance, 232 patients had no detectable MRD by flow cytometry, of which 111 were then assessed by clonoSEQ. Of these 111 patients, 42 were identified as MRD-positive by clonoSEQ. These patients had worse PFS compared to patients who were MRD-negative by flow and clonoSEQ (P=0.0006, Figure 9).[5]

Figure 9: Post-maintenance assessment of MRD by NGS in patients who were MRD-negative by flow cytometry

NCCN Guidelines

Clinical Practice Guidelines recommend MRD testing in myeloma

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend MRD testing as a Category 2A recommendation for multiple myeloma patients after each treatment stage (eg, induction, high-dose therapy/ASCT, consolidation, maintenance) at times of suspected complete response. Next-generation sequencing (NGS) is specifically included in these guidelines among the recommended tools for MRD assessment.[6] International response criteria, including IMWG and ESMO, also specifically include MRD negativity by NGS as a measure of disease response in myeloma.[7,8]

myeloma guidelines overviewvisit the NCCN website

NCCN makes no warranties of any kind whatsoever regarding its content, use, or application and disclaims any responsibility for how its content is applied or used, in any way.


This page is intended for a US-based audience.

clonoSEQ® is available as an FDA-cleared in vitro diagnostic (IVD) test service provided by Adaptive Biotechnologies to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL). clonoSEQ is also available for use in other lymphoid cancers and specimen types as a CLIA-validated laboratory developed test (LDT). For important information about the FDA-cleared uses of clonoSEQ including test limitations, please visit clonoSEQ.com/technical-summary.

Adaptive Biotechnologies does not recommend or endorse any particular course of treatment.

Citations

  • Mateos M, et al. N Engl J Med. 2018;378(6):51‌8-52‌8.
  • DARZALEX® Prescribing Information. Horsham, PA: Janssen Biotech, Inc; 2018.
  • Dimopoulos M, et al. N Engl J Med. 2016;375(14):13‌19-133‌1.
  • Martinez-Lopez J, et al. Blood. 2014;123‌(20):30‌73-30‌79.
  • Avet Loiseau H, et al. ASH 2015: Abstract 191.
  • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.7.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed July 23, 2021. To view the most recent and complete version of the guideline, go to NCCN.org.
  • Moreau P, et al. Ann Oncol. 2017;00:1-1‌1.
  • Kumar S, et al. Lancet Oncol. 2016;17(8):e3‌28-e34‌6.

Study author’s research was funded, in part, via product grants from Adaptive.

Herve Avet-Loiseau acts in a consulting capacity with Adaptive.