Advances in the Treatment of Relapsed/Refractory Multiple Myeloma: An Introduction

Beth Faiman,¹ PhD, MSN, APN-BC, BMTCN, FAAN, FAPO, Haleigh Mistry,² MS, PA-C, and Mikhaila Rice,³ PharmD, BCPS, BCOP
From ¹Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland, Ohio; ²Department of Lymphoma & Myeloma, MD Anderson Cancer Center, Houston, Texas; ³Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio.
Authors’ disclosures of conflicts of interest are found at the end of this article.
Correspondence to: Beth Faiman, PhD, MSN, APN-BC, BMTCN, FAAN, FAPO, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland, Ohio. E-mail: faimanb@ccf.org

Over the past decade, many new agents and classes of therapies have been developed for the treatment of multiple myeloma (MM), including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs), which have improved outcomes for many patients. Yet this disease remains incurable as most patients eventually relapse or are refractory or intolerant to such treatments and typically require multiple sequential therapies. Because responses decline with successive lines of therapy, heavily pretreated patients have few treatment options and face a poor prognosis. More novel therapies are urgently needed for patients with relapsed/refractory multiple myeloma (RRMM).

Advances in the Treatment of MM

Recent advances in our understanding of MM biology and tumor immunology have led to the development of novel immune-based therapies, including bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T-cell therapy. Many have demonstrated high response rates and prolonged survival in heavily pretreated patients with RRMM. Several of these agents have been approved for the treatment of RRMM following ≥ 4 prior lines of therapy (including an IMiD, a PI, and an anti-CD38 monoclonal antibody) and are now included in current treatment guidelines.

Advanced practitioners who care for patients with RRMM need to stay current on these advances since their clinical use continues to expand. However, the complexity of these therapies, including their mechanisms of action, administration requirements, and adverse event profiles, can present challenges to advanced practitioners who care for patients with MM.

Bispecific Antibodies for RRMM

A series of new articles available here on the Multiple Myeloma Resource Center cover a variety of topics related to the use of BsAbs and CAR-T for heavily pretreated patients with RRMM. The article Bispecific Antibodies for Treatment of Relapsed or Refractory Multiple Myeloma discusses the differences between these classes of agents and how they fit into the RRMM treatment landscape. This includes a review of clinical trial data supporting approval of several of these products, and for which patients BsAbs and CAR-T may be appropriate. Ongoing trials of interest are also reviewed, including those exploring combination regimens that could further improve outcomes and broaden the utility of these therapies.  

Adverse Event Management

BsAbs and CAR-T are associated with distinct adverse event profiles, and some treatment-related toxicities can be challenging to manage. In this article, some of the unique toxicities that can occur with BsAbs and CAR-T, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can be serious and even life-threatening. Early recognition of these adverse events and familiarity with guidelines regarding management are key. Step-up dosing schedules, for example, may be indicated to reduce the risk of CRS.

Advanced practitioners should recognize the need for careful monitoring during and after therapy and be familiar with recommended premedications to minimize toxicities and maintain scheduled therapy. Appropriate training and certification, including Risk Evaluation and Mitigation Strategy (REMS) programs, is also required to ensure that centers can safely deliver these therapies.

Care Coordination

Coordination of care is critical for patients receiving BsAbs or CAR-T, both between community providers and referral centers and also among the oncology multidisciplinary team. This involves choosing which patients are eligible for such agents, selecting the appropriate treatment, and optimizing the timing and sequencing of therapy. Coordination of care is critical during all three phases of patient care when administering BsAbs or CAR-T (i.e., before, during, and after treatment), particularly after step-up doses.

In this article, these issues are covered and recommendations to optimize coordination of care during the various stages of therapy are presented. A case scenario serves to highlight factors that should be taken into consideration when using these agents, including the importance of shared decision making with providers and patients. Advanced practitioners are well suited to educate patients on these complex therapies, particularly on possible treatment-related adverse events and the need for prompt mitigation.

Conclusion

This series of articles is intended to offer practical advice to advanced practitioners who may administer BsAbs or CAR-T to heavily pretreated patients with RRMM. It is hoped that they will serve to educate advanced practitioners on recent advances and best practices in the use of these novel immunotherapies for RRMM and thus improve treatment outcomes and enhance overall patient care.

Acknowledgment

Writing assistance was provided by Larry Rosenberg, PhD. 

Disclosure

Dr. Faiman has served as a consultant for Amgen, BMS, Janssen, and Pfizer. Dr. Rice has served on the advisory board for Janssen. Ms. Mistry has no conflict of interest to disclose.