How we can control multiple myeloma?

Treatment of an incurable tumor Multiple Myeloma is now standing at turning-point. Biomarker research is effective as the next wave to select best therapy with expecting "CURE"

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My father died of multiple myeloma around 20 years ago, when there were not enough therapeutic options. Although multiple myeloma is still an incurable tumor, 5 year-survival rate was dramatically improved during this 10 years by development and launching of several therapeutic agents. Proteasome inhibitors (PIs) and immunomodulating drugs (IMiDs) actually has improved myeloma therapy. And now, myeloma therapy is facing new wave of “immuno-oncology (IO) therapy” on arrival of monoclonal antibody (mAb) agents. Patient’s benefit is further improved by combination therapy of mAb with PIs and/or IMiDs. Especially, long-term survival can be achieved by mAb-initiated immunological power.

 

Thus, current myeloma therapy is standing at the turning-point, traditional chemotherapy or IO-strategic therapy.  IO-strategy seems to promise long survival with a potential of treatment-free interval.  Unfortunately, however, several clinical questions still remain in IO-strategy; (1) which regimen is fitting (2) when treatment can be stopped (3) when treatment should be re-started (4) when treatment should be switched to next one (5) how to trace/monitor disease state and efficacy.  To construct best-fitting myeloma treatment strategy, deep and further understanding of myeloma-pathophysiology and biomarker-identification are thought to be key steps.

 

Soluble form of SLAMF7 (sSLAMF7) is so unique in that it promotes myeloma cell growth by activating mitogen-activated protein kinase (MAPK) cascade via membrane-bound SLAMF7, and we found that serum sSLAMF7 level seems to be correlated with myeloma progression corresponding to ISS stage. Although the mechanism is still unclear, sSLAMF7 is released from myeloma cells, suggesting sSLAMF7 could be a predictive biomarker for malignant myeloma.  Therefore, we propose here that we can find the timing of (1) when we can stop therapy (2) when we should re-start therapy (3) when we have to add elotuzumab or to select elotuzumab-based regimen by monitoring of serum sSLAMF7. Since neutralization of sSLAMF7 is one of important actions of elotuzumab, sSLAMF7 is a promising biomarker also to select patients who could respond well to elotuzumab-based therapy. In addition, elotuzumab could be a potential agent candidate for hematologic malignancies such as smoldering/MGUS and myelofibrosis considering the high expression level of sSLAMF7.  

 

Since multiple myeloma is an incurable tumor, physicians have to try and repeat treatments from 1st treatment, 2nd treatment to 3rd treatment or later…. Anti-myeloma therapy is just like endless war. Therefore, I would like to propose here that we should add one more evaluation standard “survival post-progression (SPP)” to clinical study with anti-myeloma agents. SPP is one way to evaluate an impact of current treatment on next treatment; Low SPP agents can negatively affect next treatment and total survival will be shorten. In addition, approved regimens are thought to be classified two groups; quick/deep response regimens and mild/IO regimens. For acute phase, quick/deep regimens are preferred, and mild/IO regimens should be considered as an option for chronic phase. By considering the properties of the regimens, “Total Therapy”, where quick/deep and mild/IO regimens are combined sequentially, is suggested to be a promising therapeutic strategy for patient’s long survival with high quality of life.

 

By using biomarker and new treatment strategy, I hope further long survival of patients with expecting “CURE”!

Go to the profile of atsushi.suzuki@bms.com

atsushi.suzuki@bms.com

Japan Hematology Medical Lead, Bristol-Myers Squibb

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