International myeloma expert Maria-Victoria Mateos, Professor at the University Hospital of Salamanca-IBSAL, Spain shared her views on the frontline management of the non-transplant eligible multiple myeloma (non-TE MM) at this year’s Janssen H3 medical education symposium in Melbourne.

“In 2019, our goals of treatment are not just to extend overall survival. It’s to do it while maintaining good quality of life,” began Prof. Mateos. “To achieve this, eradication or at least major reduction of the tumour clone is required as early as possible.¹

Response criteria apply to all patients

Talking to delegates via a webcast Prof. Mateos explained how the depth of response is very important, even in the non-TE patient. “The depth of response is everything. Complete response (CR) is the typical prognostic marker we look for, but CR without achieving minimal residual disease negativity (MRD-) is no better than a partial response (PR) in terms of both progression-free survival (PFS) and overall survival (OS).² In the non-TE MM patient, it’s even more important to achieve MRD-.”²

The 2016 updates to the International Myeloma Working Group (IMWG) response criteria apply to all, Prof. Mateos reminded delegates. “Negativity inside and outside the bone marrow are important for all patients, including our older, non-TE patients.”³

To achieve this, Prof. Mateos discussed the options available today for the non-TE candidate. “There’s alkylator-based regimens using VMP, with data from the VISTA trial showing a PFS of 21 months and OS of 56 months.⁴ Then there’s alkylator-free regimens using len-dex, with data from FIRST showing a PFS of 26 months and OS of 59 months.⁵

Where are we going?

“The addition of monoclonal antibodies (MAbs) is where we are headed as the standard of care in the non-TE MM patient,”¹ Prof. Mateos added.

Daratumumab is the only MAb indicated for the frontline treatment of newly diagnosed non-TE MM in combination with VMP, but is not reimbursed on the Pharmaceutical Benefits Scheme (PBS).⁶ “The key trial for daratumumab in this setting is ALCYONE. There was a 50% reduction in the risk of progression or death in the D-VMP arm⁷  vs VMP with a median 16.5 months follow-up. At ASH in 2018, the update showed a 57% reduction in risk.⁸ We saw significantly higher response rates and a deepening of the MRD- rate with longer follow-up.⁸ We hypothesise the deepening of the response may be due to the immunomodulatory effects of daratumumab. In addition to on-tumour effects,^9-14 we know it modulates the tumour microenvironment and promotes clonal expansion of cytotoxic T cells while depleting CD38+ immunosuppressive cells.”^15-18

As PFS improves with newer agents, trials have adopted new ways to predict effects on OS. PFS2 is one of the surrogate markers adopted in the daratumumab trial to predict effect on OS. PFS2 is the time from randomisation to disease progression on the first subsequent anti-cancer therapy or death, whichever occurs first.¹⁸ “In ALCYONE,” Prof. Mateos added, “the time to PFS2 was longer in the daratumumab arm.”

Do we need to be cautious in elderly patients?

In patients over 75 years of age, Prof. Mateos reassured the audience that daratumumab added to VMP was well tolerated and the response rates were consistently better than the backbone treatment in this population as well. “Looking at safety, what we found in ALCYONE is that daratumumab did not result in more immunological or non-immunological toxicity than the backbone treatment.⁷ It was very well tolerated and produced better response rates versus VMP, even in elderly patients with or without renal impairment,” she added.^7,19

Choices in Australia comes down to continuous or time-limited therapy

“In Spain, we have access to other regimens not available in Australia, namely daratumumab added to lenalidomide-dexamethasone (len-dex). The challenge for you in Australia is working with only len-dex  or VMP in this setting. When choosing between the two remember that the trial data isn’t comparing like for like, and consideration of the continuous effect of treatment needs to be taken into account,”^5,7 she concluded.

This article was sponsored by Janssen, which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of Janssen.

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