With new drug approvals and expanded indications for new myeloma drugs at an all-time high, there is a sense of optimism in the myeloma community. Yet, even as patients experience longer survival, myeloma remains very sneaky. The disease can evolve into resistant relapse phases, demanding new therapy.

The ongoing need for new cancer treatments prompted the University of California to launch a new cancer consortium. It was announced this week that the university’s five cancer centers (San Francisco, Irvine, San Diego, Los Angeles, and Davis) will align to battle the disease, which is poised to become the leading cause of death in the state. The consortium’s goal is to study several areas at once – among them, precision approaches to treatment, geographic patterns of cancer incidence, and the factors that cause or contribute to cancer.

If the UC Cancer Consortium’s strategy sounds familiar, it may be because it is like the IMF’s International Myeloma Working Group (IMWG) approach to collaboration. I look forward to collaboration between this consortium and the California myeloma research community.

New therapy options

Right now, we need to adjust our expectations for new drug development and testing:

Single agents (preferably) or combinations must not only produce remissions, but those deep and sustained remissions must be achieved with acceptable toxicities and costs.

The recent serious toxicities with PD-1/ PD-L1 inhibitors, which led to the halt of trials, was quite a disappointment. We should be prepared for that. But, truthfully, there was a need to be cautious with these agents, which have no single agent activity in myeloma. Complex combinations (required with PD-1/ PD-L1 inhibitors) inherently raise concerns about both serious side effects and costs.

The cost of new drug development was in the news again this week. According to The New York Times, a study by Dr. Vinay Prasad and Dr. Sham Mailankody, puts the median price tag for a new drug at approximately $750 million – highly significant, but actually very low compared to typical multi-billion-dollar annual revenues that successful agents generate. 

Although controversial, this first effort attempts to identify approximate drug development costs versus potentially huge, subsequent long-term annual revenues, which more than recoup investment costs many times over. A detailed analysis of the new study appears on the Harvard Law blog Bill of Health, which features news, commentary, and scholarship in the fields of health law policy, biotechnology, and bioethics. 

Most recently, new-drug news has focused on the engineered “killer T-cell” approach using CAR T-cells. According to a Chinese media report this week, an American patient paid out of his own pocket to go to China to access what is perhaps the most promising technology among the eight or nine current pharmaceutical industry protocols in this very crowded field. The Chinese company presented extremely encouraging results at this year’s annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.  And reportedly, the American patient treated in China appears to be doing very well. 

When considering CAR-T cell therapy, we must ask: Does it meet the following priorities?

• Results in sustained and, hopefully, MRD-negative remissions. Although deep responses have been achieved, the CAR-T cells – which attack the myeloma – decrease and ultimately vanish over time, opening an opportunity for recurrent disease. 

• Is affordable. This complex, labor-intensive, and individualized therapy will certainly be more than $500,000 per patient, without the guarantee of a prolonged remission or cure. Is this too high a price for a cumbersome and potentially dangerous treatment that has challenged most development efforts so far?

The development of better new myeloma therapies depends on close partnerships between industry and investigators who are committed to patients with unmet needs, and who want a decisive active regimen.

The Chinese CAR-T cell method has become attractive because it has produced very good efficacy thus far, combined with relative safety. That China or other sites outside the US can be part of such collaborations may be the new reality and, perhaps, the wave of the future.

Safety first

This week, the FDA endorsed cautions about the use of gadolinium (a contrast agent) with MRI scans, echoing a concern I have noted for years. Retained gadolinium can trigger an NSF (autoimmune) response and maybe even act as a co-factor for cancer. A key point is that the concerns are not just for patients with impaired kidney function (the focus of early cautions), but for ALL patients receiving gadolinium, in whom some gadolinium is retained in the body and can have toxic effects.

For myeloma, there is no need to use gadolinium since different imaging techniques suffice for diagnostic purposes.  You should be aware of this FDA-issued caution if MRI imaging is used in your monitoring protocol and share your concerns with your doctor.

Stay tuned for updates on important news that impacts the lives of myeloma patients.

Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.