Patrick Daly

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Negative measurable residual disease (MRD) status is a treatment target in patients with newly diagnosed <a href="https://urbanhealthtoday.com/page/multiple-myeloma">multiple myeloma</a> (MM). However, according to authors of the phase 2 MASTER trial, modifying MM therapy based on MRD status is an unclear strategy. In the study, lead author Luciano Costa, MD, and collaborators modified or ceased daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) treatment based on MRD status in patients with newly diagnosed MM.
In their final analysis, published in The Lancet Haematology, the authors wrote treatment modifications based on MRD yielded positive outcomes and “a pathway for treatment cessation in most patients with newly diagnosed multiple myeloma.” However, patients with higher risk factors, including high-risk chromosomal abnormalities (HRCAs), did not demonstrate outcomes as promising.
<a href="https://clinicaltrials.gov/study/NCT05231629" target="_blank" rel="noopener">MASTER</a> was a multicenter, single-arm study performed at 5 academic medical centers in the United States. The primary end point was MRD negativity, defined as a cell count &lt;10−5. Secondary end points included progression-free survival (PFS) and the cumulative incidence of progression. Participants who achieved MRD negativity during or after 2 consecutive treatment phases stopped treatment and began observation with MRD surveillance.
<h2>Tracking MRD May Let Patients Cease MM Therapies</h2>
A total of 123 patients were enrolled from March 21, 2018, to October 23, 2020. The cohort had a median age of 61 years (interquartile range [IQR], 55-68 years) with 20% above 70 years of age, was 57% male, and was 76% non-Hispanic White, 20% non-Hispanic Black, and 3% another race or ethnicity. Additionally, 43% had no HRCAs, 37% had 1 HRCA, and 20% had 2 or more HRCAs. The median follow-up was 42.2 months (IQR, 34.5-46.0 months).
Among 118 patients evaluable via next-generation sequencing, 96 (81%; 95% CI, 73-88) reached the primary end point for MRD negativity; specifically, 39 of 50 with no HRCAs (78%; 95% CI, 64-88), 38 of 44 with 1 HRCA (86%; 95% CI, 73-95), and 19 of 24 with 2 or more HRCAs (79%; 95% CI, 58-93). Overall, 84 participants (71%; 95% CI, 62-79) ceased treatment and continued with MRD surveillance.
Overall, the 36-month rates of PFS in patients with zero, 1, or more than 2 HRCAs was 88% (95% CI, 78-95), 79% (95% CI, 67-88), and 50% (95% CI, 30-70), respectively. In the 84 patients who ceased treatment, the cumulative incidences of 24-month progression after cessation in the same HRCA subgroups were 9% (95% CI, 1-19), 9% (95% CI, 1-18), and 47% (95% CI, 23-72), respectively.
Given their findings, Dr. Costa and colleagues suggested treatment modulation based on MRD status was a promising strategy for most patients with newly diagnosed MM. However, they stated that “outcomes for patients with ultra-high-risk multiple myeloma, defined as those with 2 or more HRCAs, remain unsatisfactory, and these patients should be prioritized for trials with early introduction of therapies with novel mechanisms of action.”
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Related: <a href="https://urbanhealthtoday.com/post/describing-mm-therapy-efficacy-in-patients-with-severe-renal-impairment">Describing MM Therapy Efficacy in Patients With Severe Renal Impairment</a>

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Adjusting or Stopping Multiple Myeloma Treatment Based on MRD Status

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Modifying or ceasing multiple myeloma treatment based on negative measurable residual disease status may be a promising approach for newly diagnosed patients.

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