Newly diagnosed multiple myeloma: current treatment strategies, emerging therapeutic approaches and beyond

ABSTRACT

Introduction

As we have just stepped into a new decade of hopes, the mountain of knowledge learned from multiple myeloma (MM) remains unmatched among cancers. In the last decade alone, this rapid-sequence learning curve has led to regulatory approvals of eight drugs with mechanisms of actions representing five different areas of cell biology some of which made to the frontline setting, sparking debates about how to best sequence them in the treatment continuum of induction, consolidation, and maintenance and gained momentum with the realization of the implications of an effective upfront therapeutic approach with potential impact on survival.

Areas covered

This review was written with an intent to introduce the reader to the current treatment approach of a newly diagnosed myeloma patient and acquaint with promising targets and mechanistic strategies. Medline and clinicaltrials.gov databases (2000–2020) and relevant meetings (ASH, ASCO, EHA, ESMO, IMW) reports were queried and guidelines (IMWG) were reviewed to distill to expert opinion in an inundating field.

Expert opinion

Future holds promise with new targets on the horizon. It is likely that the new age of myeloma will belong to quadruplets with the addition of acellular or cellular biologics to first-generation novel agents, leading to new paradigms.

KEYWORDS:

• Multiple myeloma
• newly diagnosed myeloma
• myeloma treatment
• NDMM treatment
• newly diagnosed myeloma treatment
• myeloma quadruplets
• daratumumab quadruplets
• carfilzomib quadruplets
• BCMA
• venetoclax

Article highlights

• Given the natural history of MM that is characterized by relapses and remissions, the goal has become to obtain the best response early on, preferably with first line of treatment

• Treatment trends in NDMM follow suit with immunotherapy approaches in other fields of oncology as immunotherapies move to the front lines of therapy

• At the time of this writing, CD38, CS-1, BCMA, and several mitochondrial apoptotic pathway proteins appear to be the promising targets for NDMM therapy and are likely candidates to move up among the lines of treatment in the near future

• Following the “best-shot upfront” approach, novel cellular (eg CAR-T cells cells) and acellular (eg bispecific and drug-conjugated antibodies) approaches are being considered for earlier lines of treatment, primarily in high risk patients

• The depth of response (particularly MRD) appears to predict the survival and is more commonly integrated into the design of new clinical trials but regulatory approval as an acceptable endpoint remains unclear. Rather than a binary decision, the “durability” of MRD negativity appears to be more important in determining the outcome.

• With better understanding of the biology of pre-clinical disease states such as SMM, combination treatments targeting a cure will be explored even before clinical disease starts

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.