Monoclonal antibodies in newly diagnosed and smoldering multiple myeloma: an updated review of current clinical evidence

ABSTRACT

Introduction

Monoclonal antibodies (MoAbs) are rapidly changing the therapeutic scenario of multiple myeloma. Most of the available data, however, come from studies performed in patients with relapsed or refractory disease.

Area covered

Here, the most recent results from clinical trials that have investigated (or are investigating) efficacy and safety of MoAbs as front-line treatments in both transplant-eligible and not-eligible patients with newly diagnosed multiple myeloma, as well as in smoldering myeloma, are reviewed. PubMed reported articles before 28 March 2020, and abstracts presented at the last ASCO, ASH, EHA, and IMW meetings were considered. Among others, pertinent data regarding daratumumab, isatuximab, elotuzumab, and pembrolizumab will be analyzed.

Expert opinion

Introduction of MoAbs as first-line therapy will likely provide a significant improvement in the clinical outcome of patients with multiple myeloma. This will also require an appropriate re-positioning of salvage therapies. The role of MoAbs in smoldering myeloma appears to be promising, but adequate follow-up is needed.

KEYWORDS:

• Multiple myeloma
• smoldering myeloma
• daratumumab
• isatuximab
• elotuzumab
• pembrolizumab
• nivolumab
• check-point inhibitors

Article highlights

• Adding daratumumab to current standard of care for patients with NDMM not eligible for transplant procedures (VMP, Rd) significantly improves response rates, quality of response (particularly the achievement of MRD-negativity), and PFS/PFS2 across different prognostic subgroups; preliminary results on OS also appear better for patients treated with these daratumumab-containing combinations (DVMP, DRd).

• Likewise, the addition of daratumumab to VTd (DVTd) has demonstrated to be superior to VTd alone in NDMM patients eligible for transplant procedures in terms of quality of response (including MRD) and PFS across patients with high-risk cytogenetics and advanced ISS disease stage.

• The safety profiles of daratumumab-containing regimens are similar to those of comparators without daratumumab, excluding manageable initial infusion-related reactions. Infections, however, may represent a possible issue.

• The use of daratumumab within other quadruple combinations (including bortezomib, lenalidomide, carfilzomib, cyclophosphamide, or ixazomib) has provided promising results in phase 2 studies and is currently under investigations in randomized trials.

• Subcutaneous daratumumab reduces times of administration to just a few minutes, showing comparable efficacy, less incidence of infusion reactions, strong reduction of treatment burden, and improvement of patient’s satisfaction as compared to the intravenous route.

• Isatuximab and elotuzumab are currently being investigated as induction, consolidation and maintenance treatments in phase 2–3 trials of both transplant eligible and not-eligible NDMM in combination with other agents.

• Based on the current available data, the use of checkpoint inhibitors is not recommended in NDMM outside of clinical trials.

• Preliminary results of MoAbs in smoldering myeloma appear to be promising, but longer follow-up is required to draw definitive conclusions.

Acknowledgments

The authors greatly thank Dr. Donata Grazia Coladonato and Dr. Vito Pier Gagliardi for their support to the final draft of the paper.

Declaration of interest

P. Musto has received honoraria and/or served on the scientific advisory boards for Celgene, Janssen, Takeda, Bristol-Myers Squibb, Amgen, Novartis, Gilead, Jazz, Sanofi, and Abbvie. He has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer of this manuscript discloses receiving consulting fees from Sanofi and Janssen. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.