Robust multiple myeloma treatment program holds promise

At the Medical College of Wisconsin (MCW), the multiple myeloma program is a robust program that has grown throughout the years.

Providers see approximately 300 new multiple myeloma patients each year at MCW, and perform approximately 120 to 150 stem cell transplant-based treatments annually for myeloma alone. In 2016, providers saw a total of 928 individual multiple myeloma patients.

MCW is home to the Center for International Bone and Marrow Transplant Research (CIBMTR) and Bone Marrow Transplant Clinical Trials Network (BMT CTN). Approximately,15 to 20 investigator-initiated and industry-sponsored studies for myeloma are ongoing.

MCW multiple myeloma experts, Parameswaran Hari, MD, interim chief, professor of medicine, hematology and oncology, and Binod Dhakal, MD, MS, assistant professor of medicine, division of hematology/oncology, talked to Managed Healthcare Executive (MHE) about opportunities for healthcare executives to succeed in this area, as well as challenges and how to overcome them.

MHE: What opportunities exist for healthcare executives in multiple myeloma?

Hari: We have a number of research studies (both clinical and translational) looking into understanding the unique disease mechanisms and the treatment approaches. One of these is to identify the novel targets that are expressed solely on the surface of multiple myeloma cells by using mass spectroscopy. This study hopes to find some potential druggable targets for further development. One of the ideas that we are working on currently is to understand the potential role of micro-RNA in perturbation of osteoblast maturation in multiple myeloma bone disease (MMBD). With an improved understanding of molecular networks involved in multiple myeloma bone disease; our study hopes to find a potential predictive biomarker for MMBD and also provide a framework for the clinical development of novel therapeutics.

Recently there has been interest in developing immunotherapeutic targets in multiple myeloma (MM) that enable a patient’s own immune system to develop effective myeloma specific immune responses. We have a number of studies looking into the immune approaches in MM:

• The BMTCTN 1302 study explores the role of allogeneic stem cell transplant in patients with high-risk multiple myeloma.

• The CTN 1401 study uses a more personalized immune treatment by generating a myeloma cell-dendritic cell fusion vaccine after autologous stem cell transplant (ASCT).

• We just completed our own investigator-initiated trial looking at the role of immune checkpoint inhibitors after transplant to enable myeloma specific immunity.

• The other study uses the natural killer cells (induced or third party) as an immune cellular approach in heavily treated patients.

• We are also in the process of developing the first ever-dual CAR-T cell therapy in B cell malignancies including multiple myeloma.

• Furthermore, in collaboration with investigators from University of Wisconsin, Madison, we are working to develop a potential biomarker for immune therapy in MM.

Next: What promising developments can we anticipate?

MHE: What are the promising developments in multiple myeloma?

DhakalDhakal: Significant progress has been made in the field of MM over the last decade, and this has translated into a three- to four-fold increment in the median survival.  In 2015, we have four new drugs approved for the disease including the monoclonal antibodies.  The disease diagnostic criteria have been revised and the former high-risk smoldering myeloma is now considered multiple myeloma needing treatment. Stringent response criteria including the minimal residual disease has been incorporated in the response guidelines and will soon be used in the clinical trials. Understanding clonal progression, evolution, and tides has helped both in elucidating the disease behavior and expanding the therapeutic choices.  With the introduction of both the proteasome inhibitor and the immunomodulator as a standard induction treatment, we have achieved an unprecedented response rates. Studies exploring the role of ASCT in the context of modern induction regimens have shown that high-dose therapy is associated with superior response rates and progression free survival.  

Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both.

MHE: What are healthcare executives’ major challenges in the area of multiple myeloma?

Hari: The single most important challenge for healthcare executives in this area is the increasing of cost of care. Newer therapeutics have changed the outcome for patients dramatically with average survival doubling in the past decade. However, the paradigm of care involves continuous therapy with targeted medications. The annual average cost of care even in patients maintaining a remission can exceed $100,000, while the cost of care for relapsed myeloma could be three to four times higher. Getting to a model of affordable care without compromising the quality of care or rationing therapies is a challenge.

Other issues include maintaining quality of life of survivors and maintaining standards of care for the majority of patients. It has been shown that the utilization rate for autologous transplant for myeloma even among transplant eligible patients is less than 50%, and that minorities are especially likely to not receive such therapy.

Next: How can we meet these challenges?

MHE: How can these challenges be met or avoided?

Dhakal: These challenges can only be addressed through a systematic plan that ensures all patients have access to the best specialized myeloma care, access to second opinion with a myeloma expert, access to stem cell transplant and clinical trials. While the majority of myeloma care can be delivered in the community in a cost-effective fashion, a myeloma specialist has to remain involved in a consultative fashion. This can ensure the delivery of state of the art care and access to clinical trials. Similarly, for affordable care, insurers, hospitals, patients and other stakeholders such as employers should come together with pharma to discuss rising costs of care delivery.