Ten ways multiple myeloma treatment is changing

As steady improvements continue in the treatment of multiple myeloma, it’s important for managed care executives to get out in front of the changes on the horizon. 

Scott

“Several exciting new drugs are in the market or on the verge,” says Jeffrey Scott, MD, an oncologist and chief medical officer of Integra Connect. “This means that more patients are living longer and better, and treatment increasingly resembles chronic care.”

He adds that treatment improvements across all care settings are leading to fewer complications and fewer unnecessary costs. “This trend is accelerating in the wake of CMS value-based care programs such as the Oncology Care Model.”

Several classes of therapies are available for treating relapsed multiple myeloma, says Sam Santhosh, founder, chairman and global CEO of MedGenome. They include:

• Immunomodulatory drugs (thalidomide, lenalidomide)

• Proteasome inhibitors (bortezomib, carfilzomib)

• Histone deacetylase inhibitors (panobinostat)

• Monoclonal antibodies (daratumumab, elotuzumab)

• Alkylating agents (cyclophosphamide)

“Combination therapies, specifically synergistic combinations result in deep responses of longer duration,” Santhosh says.

With so much going on in multiple myeloma treatment, it can be difficult to keep track of the major developments. Here are 10 things experts say healthcare executives should know.

1. Over the last decade, there’s been unprecedented outcomes improvements

Messerschmidt

“New therapies in myeloma are being approved and brought into investigation at an ever-increasing rate,” says Gerry Messerschmidt, MD, FACP, chief medical officer of Precision Oncology. “These are no longer just new drugs but new biologics/immune therapies and cellular therapies such as CAR T-cell infusions. Combinations of drugs and immune and cellular therapies theoretically have the ability to dramatically impact myeloma outcomes, e.g., potential longer-term disease-free survival. The costs of these many element therapies will be ever increasing but if they result in significant fractions of patients developing long-term disease-free survival, overall healthcare costs could decrease.”  

Dhakal

Binod Dhakal MD, MS, assistant professor of medicine, Division of Hematology/Oncology, Medical College of Wisconsin, says promising new immunology methods include antibody-based therapy, cellular therapy including CAR-T cell therapy, and vaccine-based approaches. He adds that lenalidomide maintenance after stem cell transplantation results in improved overall and progression-free survival.

Mary Kwok, MD, FACP, USA, Hematology-Oncology, Murtha Cancer Center, Walter Reed National Military Medical Center, adds that the FDA approved indications for currently available drugs were expanded to include new combinations of medications, and promising clinical trials are ongoing, particularly studies investigating CAR T-cells to treat myeloma.

2. Improved outcomes and more treatments may mean higher costs

As patients live longer and treatment options expand, payers need to find ways to partner more closely with oncology practices and accelerate the design of value-based care models, says Scott. “The goal should be to prevent avoidable costs and reduce complications associated with treatment. That means equipping oncologists to better manage these patient populations holistically across all settings of care and elements of their health and well-being.”

3. Relapse remains an issue

Morgan

“Despite the vast improvement, there remains a proportion of patients who relapse and are more likely to have aggressive disease that is refractory to therapy,” says Gareth Morgan, MD, PhD, director, University of Arkansas for Medical Sciences Myeloma Institute.

Identifying these high-risk patients at diagnosis and implementing therapeutic approaches that can overcome treatment resistance is crucial, he says. “This requires a change that focuses on the use of genetic analyses to segment myeloma at the molecular level to enhance risk segmentation and develop biologically-stratified, in addition to targeted- and precision-immunotherapy treatment approaches,” he says. 

4. The diagnostic approach to myeloma is evolving

In 2014, the International Myeloma Working Group updated the diagnostic criteria for myeloma to include patients previously identified with a precursor disease, “ultra high-risk smoldering myeloma.”

“This was based on an improved understanding of the biology of myeloma and allowed patients to begin effective therapies before the development of organ damage such as renal dysfunction, anemia, hypercalcemia or lytic bone lesions,” says Kwok, assistant professor of medicine, Uniformed Services University Associate Training Program Director, Hematology-Oncology Fellowship Program.

“Modern imaging, such as PET-CT and MRI are being used more frequently to make the diagnosis of myeloma before the development of severe bone lesions,” Kwok says. “After treatment, very sensitive techniques such as next-generation sequencing or next-generation flow cytometry are being employed to detect myeloma at very low levels.” This helps determine the best responses to treatment and may have prognostic implications, she says.

Next: Five more changes

5. Multiple myeloma has transformed from an acute to chronic disease

Matsui

“As novel therapies are more effective and safer, this allows them to be given weekly to daily fashion over much longer periods of time,” says William Matsui, MD, myeloma specialist at the Johns Hopkins Kimmel Cancer Center.

6. Inpatient and outpatient treatment is increasing

Newer drugs are often given in the clinic setting and being administered in combinations of three drugs and perhaps more, says Messerschmidt. “Bone marrow transplant-or more recently referred to as hematopoietic stem cell transplant or HSCT- is often an inpatient procedure and with common associated toxicities result in re-admissions of prolonged hospitalizations,” he says. “These autologous-from self-HSCTs are becoming so easy to perform between the hematologist and the blood bank, growth to community settings could become significant if data continues to demonstrate benefit.”

7. Novel technologies are gaining momentum

Next-generation sequencing has altered the paradigm of multiple myeloma treatment by revealing existence of clones that have unique genetic architecture, says Santhosh.  These findings have been translated into personalized therapies-creating combinations with different drug classes to increase patient survival. For example, targeting MAPK pathway with approved inhibitors, such as BRAF inhibitor or MEK1 inhibitor. “The disease is genetically highly heterogeneous and it is possible to stratify patients into different risk categories, which dictate choice of therapy and clinical outcomes,” he says.

8. The addition of the monoclonal antibodies into the myeloma armamentarium is a significant advance

Voorhees

The clinical activity and acceptable safety profile of daratumumab, a CD38-targetd monoclonal antibody, has facilitated its incorporation into existing myeloma regimens in the relapsed space. This has led to regulatory approvals of daratumumab in combination with lenalidomide and dexamethasone, bortezomib and dexamethasone and pomalidomide and dexamethasone, says Peter Voorhees, MD, Levine Cancer Institute.

“There are ongoing studies in newly diagnosed patients, and the myeloma community is cautiously optimistic that daratumumab will eventually receive approval as part of frontline regimens in multiple myeloma,” Voorhees says.

9. Minimal residual disease (MRD) testing is a highly sensitive way of detecting trace levels of disease in patients in complete response

Treatment regimens that produce higher rates of MRD negativity have been shown to be associated with longer progression-free and, in some cases, overall survival, Voorhees says. However, it is not yet known if MRD testing can be used to make clinical decisions about a patient’s care. Voorhees says that this question is being addressed in active or planned clinical studies.

10. Two recent multiple myeloma drug trials have halted.

Santhosh

Genetic heterogeneity of multiple myeloma, and given that it responds to immunomodulatory drugs, makes it an attractive target for checkpoint blockade therapies, Santhosh says.

However, two recent clinical trials were stopped after interim analysis revealed that use of Merck’s pembrolizumab (Keytruda), a PD-1/PD-L1 cancer drug, in combination with immunomodulatory drugs (lenalidomide or pomalidomide), increased risk of death by more than 50% compared to the control arm. The FDA released an alert and summary of these findings.

Tracey Walker is content manager for Managed Healthcare Executive.