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Current Approach to Managing Patients with Newly Diagnosed High-Risk Multiple Myeloma

  • Multiple Myeloma (P Kapoor, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

With rapid advances in the therapeutic landscape and biological insights in multiple myeloma, it is critical to identify and strategically manage high-risk patients to achieve best outcomes with currently available drugs. The purpose of this review is to summarize the management of high-risk myeloma with a focus on recent advances in the field.

Recent Findings

The most widely accepted definition of “high-risk” is the Revised International Staging System (R-ISS) stage 3 disease, which includes high tumor burden (ISS stage 3) and high-risk FISH cytogenetics or an elevated lactate dehydrogenase level. A major advance in the management of high-risk patients is insight into the importance of achieving and sustaining minimal residual disease (MRD) negativity, which is an influential equalizer for long-term outcomes. Quadruplet pre-transplant induction regimens incorporating an anti-CD38 monoclonal antibody (mAb), proteasome inhibitor (PI: bortezomib or carfilzomib), lenalidomide, and dexamethasone should be strongly considered in high-risk patients given higher odds of getting to MRD negativity with these regimens compared to triplets. In transplant-eligible patients, upfront transplant does lead to a higher rate of sustained MRD negativity and superior PFS compared to delayed transplant. The role of tandem transplant in the context of bortezomib-lenalidomide-dexamethasone (VRD) induction therapy is unclear. Post-transplant maintenance therapy should include lenalidomide in combination with either bortezomib or carfilzomib until progression. For transplant-ineligible patients, VRD or daratumumab-lenalidomide-dexamethasone (DRD) until progressions are both reasonable and choice should be individualized based on patient-related factors.

Summary

Outcomes of high-risk myeloma patients have improved in the last decade with the use of modern 3-drug induction regimens incorporating a PI and an immunomodulatory drug, with potential for further improvement as we bring anti-CD38 mAb upfront. MRD assessment will play a major role in treatment modification at several key time-points in the future such as pre-transplant, pre-maintenance, and yearly on maintenance therapy.

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Authors and Affiliations

  1. Department of Internal Medicine, St. Barnabas Hospital Program, Bronx, NY, USA

    Naimisha Marneni

  2. Division of Hematology/Oncology, Department of Medicine, Multiple Myeloma and Amyloidosis Program, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Fort Washington Ave G, New York, NY, 10032, USA

    Rajshekhar Chakraborty

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Correspondence to Rajshekhar Chakraborty.

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Marneni, N., Chakraborty, R. Current Approach to Managing Patients with Newly Diagnosed High-Risk Multiple Myeloma. Curr Hematol Malig Rep 16, 148–161 (2021). https://doi.org/10.1007/s11899-021-00631-7

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