In Updated Treatment Guidelines for MM, Supportive Care Still Plays a Key Role

On the first day of the National Comprehensive Cancer Network (NCCN) 23rd Annual Conference, in Orlando, Florida, Shaji K. Kumar, MD, a consultant in the division of hematology and professor of medicine at Mayo Clinic Cancer Center, presented updates to NCCN’s treatment guidelines for multiple myeloma (MM).

There are expected to be 30,770 new cases of MM in the United States in 2018, and these cases could lead to 12,770 deaths, said Kumar. The disease, which presents as lytic bone disease, hypercalcemia, renal insufficiency, anemia, and infections, accounts for about 1.8% of all cancers, and about 18% of hematological malignancies in the United States.

NCCN’s myeloma panel has categorized treatment regimens as preferred treatments, other recommended treatments, or treaments that are useful under certain circumstances. The guidelines provide treatment guidance based on evidence from clinical trials, relative efficacy and toxicity, comorbidities, the nature of the disease, and access to treatment agents.

In the clinical presentation of solitary osseous or solitary extraosseosus MM, NCCN recommends radiation therapy to the involved field plus surgery, with follow-up every 3 to 6 months. In primary progressive disease, or cases of response followed by progression, the patient should be restaged with a myeloma workup.

Kumar highlighted the fact that MM may be “smoldering,” or asymptomatic, with no lesions or one lesion present in an magnetic resonance imaging (MRI) evaluation. Smoldering MM may evolve into overt disease at a rate of approximately 3% per year. If smoldering MM is identified (an accurate diagnosis requires advanced imaging, such as an MRI), observation at 3- to 6-month intervals is appropriate. Because patients are asymptomatic and treatments are toxic with no evidence to suggest that they improve survival in this group, no treatment is warranted. In cases of smoldering MM, risk stratification is key, and high-risk patients should be considered for clinical trials, even though treatment outside of clinical trials is not recommended.

If MM becomes symptomatic, myeloma therapy, bisphosphonates or denosumab, and supportive care are indicated. In patients who are candidates for stem cell transplants, exposure to myelotoxic agents should be limited to avoid compromising stem cell reserves. Preferred regimens for these patients include bortezomib, lenalidomide, and dexamethasone therapy, or bortezomib, cyclophosphamide, and dexamethasone.

“Once we have initial therapy completed, patients should be considered for autologous stem cell transplant,” said Kumar, pointing to a study¹ in which patients who underwent such a transplant had better outcomes than those who received bortezomib, lenalidomide, and dexamethasone alone; 79% of the transplantation group, versus 65% of the non-transplantation group, had minimal residual disease not detected during the study, with a complete or very good partial response.

For patients who are not candidates for transplant, preferred treatment regimens are bortezomib, lenalidomide, and dexamethasone; lenalidomide and low-dose dexamethasone, and bortezomib, cyclophosphamide, and dexamethasone. In cases of relapsed disease, therapy for previously relapsed disease, a clinical trial, or stem cell transplantation should be considered.

However, Kumar cautioned, biochemical relapse does not always warrant the start of a new therapy, and the patient’s age and comorbidities—as well as prior and residual toxicities—should be taken into consideration before starting a new therapy. The oncologist should treat to maximum response and maintain the use of 1 drug until progression or tolerability have been reached.

Supportive care is also critical to treating MM; “Even though we have all these fancy, effective drugs,” said Kumar, “supportive care still plays an important role in multiple myeloma.” All patients receiving primary care, he said, should be given bisphosphonates or denosumab, and the clinician should monitor for renal dysfunction and osteonecrosis of the jaw with the use of bisphosphonates. Hydration and bisphosphonates (preferably in the form of zoledronic acid) can be used in case of hypercalcemia, plasmapheresis can be used for symptomatic hyperviscocity, and erythropoietin may be used in cases of anemia. To guard against thrombosis, “I think it’s important to make sure these patients are on a full dose of aspirin.” said Kumar.

Finally, the clinician should screen for infection, provide intravenous immunoglobulin therapy in life-threatening infections, and prophylaxis against pneumonia, herpes, and fungal infections may be warranted. To maintain renal function, contrast should be avoided in imaging, and a renal biopsy may be clinically indicated.

Reference

1. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med 2017;376:1311-1320. doi: 10.1056/NEJMoa1611750.