Triplet therapies – the new standard of care for multiple myeloma: how to manage common toxicities

ABSTRACT

Introduction: Multiple three drug combination regimens have been approved for the treatment of multiple myeloma in the last few years. Triplets have become the new standard of care for transplant eligible and ineligible patients with newly diagnosed as well as relapsed multiple myeloma. Novel agents have a unique profile of side effects. The management of toxicities is important to maintain quality of life and maximize treatment duration and benefit.

Areas covered: This article reviews efficacy data, incidence of key adverse events and provide recommendations and expert opinion regarding how to manage common toxicities in triplet therapies. Relevant publications and abstracts were searched in PubMed, ASH, ASCO and EHA meetings. Guidelines from IMWG, NCCN, ESMO and ASCO, published trial protocols and prescribing information were used to formulate recommendations for the management of toxicities.

Expert commentary: Side effects are a critical factor guiding the selection of optimal chemotherapy regimens for multiple myeloma. The majority of toxicities encountered with triplet therapies are reversible and can be readily managed with supportive care and dose modifications.

KEYWORDS:

• Myeloma
• triplets
• three-drug
• management
• adverse
• toxicity

Key issues

• Triplets in multiple myeloma are the new standard of care for both transplant eligible and ineligible patients with NDMM as well as RRMM.

• The majority of the side effects due to novel agents are different from conventional chemotherapy and require unique management strategies.

• Most of the side effects of triplets in MM are reversible and can be effectively managed with supportive care.

• Thresholds for dose modifications or treatment delays due to cytopenias differ among various drugs used in triplet combinations.

• Antiviral shingles prophylaxis is recommended with proteasome inhibitor and monoclonal antibody based regimens.

• VTE prophylaxis is recommended with immunomodulatory drug based combinations.

• Peripheral neuropathy due to bortezomib can be reversible, but requires early dose modification or substitution with second generation proteasome inhibitor that are less likely to cause neuropathy.

• Cardiovascular risk factors should be optimized prior to initiation of carfilzomib.

• Patients with asthma and COPD are at increased risk of IRR with daratumumab and require enhanced measures to prevent reactive airway flare.

Declaration of interest

A Paner has consulted for Celgene, Amgen, Takeda, and Janssen Pharma. The authors have 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

One reviewer declares honoraria from Janssen, Celgene, Takeda, Bristol-Myers Squibb, and Amgen but peer reviewers have no other relevant financial relationships to disclose.

Additional information

Funding

This paper was not funded.