Microenvironment May Predict Sustained MRD Negativity in Newly Diagnosed Myeloma

A study presented at the 2022 American Society of Hematology (ASH) annual meeting examined how changes in the microenvironment correlated with sustained measurable residual disease (MRD) negativity in patients with newly diagnosed multiple myeloma treated with daratumumab (Darzalex), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (dara-KRd).

In this exclusive MedPage Today video, Eileen Boyle, MD, PhD, of the Perlmutter Cancer Center at NYU Langone Health, discusses the findings.

Following is a transcript of her remarks:

So in order to identify the determinants of response, we performed single-cell analysis on the microenvironment of patients that received dara-KRd. We were able to identify factors that were associated with a favorable microenvironment.

Indeed, we saw that patients that had interferon-producing NK [natural killer] cells did better than patients that did not. We also saw that the patients that had these interferon-producing NK cells had changes in their monocyte population and a very diverse T-cell repertoire. And after eight cycles of treatment, that inflammation disappeared, and the T-cell population became very small and lost a lot of its diversity. Monocytes became more sleeping and NK cells lost the production of interferon gamma.

At the other end of the spectrum, patients that did poorly did not show an increase in their monocyte population, had very low levels of diversity in their T-cell repertoire, and early on, sleeping-type monocytes.

And after treatment, we nonetheless, after eight cycles, we saw some evidence of activation of the monocyte macrophage population, and some changes in the NK population and T-cell repertoire that became more diverse, suggesting the elements of the microenvironment was still present and could potentially be manipulated.

So the clinical takeaway is probably that we can identify factors beyond genetics that determine the response, and the composition of the microenvironment in bone marrow of myeloma patients is a function of time and response to therapy. And given that the cells are present at the microenvironment, there may be some scope to manipulate the NK response, the T-cell response after eight cycles of treatment, which is relatively early on in order to deepen the response rates in newly diagnosed myeloma.