COMMENTARY

Joseph Mikhael: ASCO 2017 Takeaways in Myeloma

Joseph Mikhael, MD, MEd

Disclosures

June 26, 2017

Multiple myeloma remains a complex and rapidly changing field in oncology. Although it accounts for only 2%-3% of oncologic practice, it is one that continues to evolve rapidly both in the science that defines the disease and the treatments available to control it.

Several myeloma abstracts were presented at the American Society of Clinical Oncology (ASCO) 2017 annual meeting that I initially reviewed on Medscape’s ASCO 2017 Live Blog. But what do these studies mean for clinical practice today? Although no cataclysmic changes to my practice have been made as a result of these studies, there were several important take-home messages.

Carfilzomib in frontline myeloma is becoming more prolific. A large Italian study demonstrated the feasibility of using carfilzomib in frontline therapy combined with either cyclophosphamide-dexamethasone (KCD) or lenalidomide-dexamethasone (KRD). Although this is being done frequently in the United States, it has been on the basis of limited data, and most patients are treated frontline with bortezomib and not carfilzomib. Both regimens of KCD and KRD were quite well tolerated and had high response rates. This helps our practice right now as it further justifies the use of carfilzomib upfront, which is particularly attractive in patients with preexisting neuropathy or in high-risk disease.

Daratumumab in early relapse combined with bortezomib or lenalidomide is a new standard of care. Last year at ASCO, the CASTOR study of daratumumab plus or minus bortezomib was a plenary abstract. A year later, the combination of daratumumab plus bortezomib—and indeed daratumumab plus lenalidomide—is now FDA approved. Several abstracts this year noted updated data from these two studies that validate their use in both high-risk and standard-risk patients.

Monoclonal antibodies in frontline myeloma are not far away. Soon, daratumumab will likely be used not only in relapsed myeloma but as frontline therapy as well. Although preliminary, encouraging studies indicate that it can be added to standard induction regimens prior to transplant, such as bortezomib-lenalidomide-dexamethasone or carfilzomib-lenalidomide-dexamethasone. Stay tuned!

Denosumab will play a role in bone disease in myeloma. Bony agents are critical in myeloma to prevent and repair bone damage. Although previous studies did not demonstrate significant benefit of denosumab in myeloma bone disease, a large trial was presented comparing zoledronic acid and denosumab. Denosumab was noninferior but resulted in less renal damage and thus may be the better choice in patients with pre-existing renal disease. Although this has yet to be formally FDA approved, I anticipate its use in the very near future. I would consider it now in patients with compromised renal function.

CAR T–cell therapy is coming to myeloma. CAR (chimeric antigen receptor) T-cell therapy is the latest wave in hematology and has been validated in various forms of leukemia and lymphoma. Soon it may also be used in myeloma. A late-breaking abstract was presented by a Chinese group that demonstrated the feasibility of this approach, with 34 out of 35 patients responding. Toxicity, including cytokine release syndrome, does remain an issue but is quite manageable in most patients. My take on this is that the science is evolving, and with time this approach will be refined and less toxic. In the meantime, I would suggest that this is not ready for prime time and should be explored for myeloma only in clinical trials.

Many other abstracts were presented that are likely to influence the field in the future, including those on novel monoclonal antibodies such as isatuximab and other immunotherapy approaches. Myeloma remains incurable, but with these approaches we hope that it will become a chronic disease in the not-so-distant future.

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