Challenges in the Management of Relapsed/Refractory Multiple Myeloma

The following article features coverage from the 2022 Oncology Nurse Advisor Summit. Click here to read more of Oncology Nurse Advisor‘s conference coverage.

Multiple myeloma (MM) is an incurable plasma cell neoplasm that causes excess paraprotein secretion and subsequent bone, bone-marrow, immune, neurologic, and renal dysfunction. Numerous treatment options are available, and patients with the disease will achieve a deep and durable remission. However, relapse occurs in nearly all patients. Recognizing relapse and when to initiate treatment is a critical component of managing the care of patients with MM.

One challenge for oncology nurses is to keep patients engaged in their healthcare during both times of remission and relapse to optimize their outcomes, explained Beth Faiman, PhD, MSN, APRN-BC, AOCN, FAAN, a nurse practitioner in the department of hematology and medical oncology at the Cleveland Clinic Taussig Cancer Institute in Ohio, during a presentation at the 2022 Oncology Nurse Advisor Summit.

Diagnostic Workup

A common investigative workup that can inform a diagnosis of MM and severity of disease, as well as what next steps may be appropriate, include CBC with differential counts, complete metabolic panel (CMP) and electrolytes, serum electrophoresis with quantitative immunoglobulins (SPEP), and B2 microglobulin (B₂m) and lactate dehydrogenase (LDH).

Decreased hemoglobin, white blood cell (WBC) and platelet counts; increased creatinine, Ca++, uric acid, and decreased albumin; plus increased M protein in serum and possibly decreased levels of normal antibodies on SPEP are all possible findings with myeloma. B₂m and LDH, measures of tumor burden, are increased. Patients with higher levels of B₂m and LDH could have a higher stage disease and may not do as well.

“Twenty-four-hour urine protein electrophoresis with immunofixation is so important,” Dr Faiman said. It determines the level of Bence-Jones, a monoclonal protein, passing through the kidneys in urine. An increase in this protein could indicate kidney damage.

Bone marrow aspirate and biopsy, and cytogenetics are prognostic measures. FISH is a very important genetic test used to diagnose leukemia, lymphoma, and multiple myeloma.

Although skeletal survey has been the gold standard, the International Myeloma Working Group has said whole-body CT/PET or MRI are more sensitive tests for detecting osteolytic lesions, osteoporosis, or extramedullary disease.

The standard course of treatment for multiple myeloma is induction therapy (generally 3 to 4 cycles, with 3 to 4 drugs); autologous stem cell transplantation (ASCT) for those who are eligible, with or without consolidation therapy; maintenance; and treatment of relapsed disease. Supportive care includes management of adverse effects and bone-modifying agents.

Patients with MM should be continuously assessed for eligibility for ASCT. Early referral to the transplant center is important, even for older patients.

MM is a progressive disease. Most patients initially have monoclonal gammopathy of undetermined significance (MGUS). Patients have extra protein in their blood or urine, but may not have serious disease. They should undergo blood and urine testing every 6 to 12 months. However, over 20 years, their condition may catapult to acute MM.

Recognizing Relapse and Refractory Disease

First relapse occurs approximately 3 to 4 years after initial diagnosis, and each subsequent relapse tends to occur over a shorter period of time. At relapse, regimens can be new drugs or a mix and match of new combinations of drugs used in induction therapy or prior relapse.

MM becomes refractory to therapy at some point, and may develop resistance to several drugs after multiple lines of therapy. Yet studies have shown that many patients who go into remission might not need another treatment, noted Dr Faiman. Therefore, goals of therapy should be continually reassessed throughout the disease course.

Slowly increasing M protein levels is a biochemical relapse. Clinical relapse is determined by presence of 1 or more of the following criteria:

• Increase in size of existing plasmacytomas, hypercalcemia (>11 mg/dL)
• Hemoglobin ≥2 g/dL not related to therapy or nonmyeloma-related conditions
• Serum creatinine ≥2 mg/dL from the start of therapy and attributable to myeloma
• Hyperviscosity related to serum protein
• Increase of 25% from the lowest confirmed response value 1 or more of these criteria: serum M-protein ≥0.5 g/dL; urine M-protein ≥200 mg/24 hours; if no serum or M protein can be measured, the difference between monoclonal and polyclonal free light chain levels must increase by more than 10 mg/dL 

In a step-wise progression, consider observation and close monitoring for a patient with asymptomatic biochemical relapse on 2 consecutive assessments. In the case of asymptomatic high-risk disease, rapid doubling time, or extensive marrow involvement, consider patient-/disease-specific treatment and monitor carefully. Symptomatic or extramedullary disease warrants initiating treatment.

MM relapse is classified as early (1-3 prior lines of therapy), late (>3 prior lines of therapy), or refractory. Heavily pretreated MM may be categorized as triple-class refractory, defined as refractory to a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody (mAb); or penta-drug refractory, defined as refractory to 2 or more PIs, 2 or more IMiDs, and an anti-CD38 therapy.

Supportive Care and Survivorship

The nurse’s role in managing the patient in remission or relapse is to keep patients engaged throughout remissions as well as relapses. Although many patients in a long-term remission might not ever need another treatment, they could experience a late effect that could lead to a relapse so you want to keep them informed and provide support resources.

Most patients develop bone disease. Those taking bone-modifying agents should be evaluated routinely, with possibly less frequent testing at their physician’s discretion. Monitoring for new or worsening bone pain and serum calcium levels also is important. Imaging studies may be needed depending on the type of pain.

M protein and cast levels in active MM and high calcium are risks for renal dysfunction. Some medications (contrast dyes, NSAIDs) should be avoided. Hydration is essential to maintain kidney health.

MM is an excess of proteins, which could increase risk of blood clots, therefore venous thromboembolism prevention is a concern. “Everybody should be on at least a baby aspirin,” Dr Faiman suggested.

Health maintenance and healthy lifestyle habits are very important, including maintaining an ideal weight and physical exercise. Patients should discuss their MM with their primary care provider, especially if they have comorbidities such as diabetes, hypertension, or other chronic conditions.

Infection prevention is another important component of support care. Immunizations are recommended; however, patients with MM should not receive live vaccines. COVID, pneunomococcal (13 and 23), inactivated seasonal influenza, and recombinant shingles vaccine are all recommended.

Many centers are not certified to provide bispecific T-cell and CAR-T therapies. Nurses should build a relationship with those facilities, and get referrals for patients so these treatments are available to the patient when appropriate.

“Patients are considered survivors at diagnosis,” Dr Faiman said, and will need a comprehensive survivorship plan that comprises their medical, disease, treatment, and lifestyle information, with appropriate recommendations and referrals. The survivorship care plan also should list key contacts, including the primary care provider, specialists treating any comorbidities, oncology/hematology care team, caregivers, advocates, and other members of the patient’s support team.

Read more of Oncology Nurse Advisor’s coverage of 2022 Oncology Nurse Advisor Summit by visiting the conference page.

Reference

1. Faiman B. Setting the Stage for Success: Caring for Patients with Relapsed or Refractory Multiple Myeloma. Oral presentation at: 2022 Oncology Nurse Advisor Summit; March 25-27, 2022.