Case 4: Molecular Testing and CAR T-Cell Therapy in Myeloma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDC. Ola Landgren, MD:Pei, is there any testing that you think should be done, from a pathological standpoint, beyond what I mentioned here, for a patient who is looking for CAR [chimeric antigen receptor] T-cell therapy?

Pei Lin, MD:Sure. As we discussed in the last case, we should perform a FISH [fluorescence in situ hybridization] panel on this patient to see whether there is a high-risk FISH abnormality suggesting del(17p) [17p deletion]. In our institution, we would also perform NGS [next-generation sequencing] to look for theRASmutation as well asTP53, as Dr Chari mentioned earlier. TheTP53deletion could now be biallelic instead of monoallelic. For a patient who is considered for CAR T-cell therapy, a flow cytometry study can be done using the antibody against BCMA [B-cell maturation antigen] to detect the expression level on the plasma cells—the neoplastic cells. These tests can be performed to help further characterize those malignant cells.

C. Ola Landgren, MD, PhD:In the initial eligibility criteria for this study, for the phase I part, they required 50% or higher BCMA expression. But as the study went on, this was amended. I believe this was removed from the eligibility criteria. How could that be? Could you comment on BCMA testing for the purpose of CAR T-cell therapy?

Pei Lin, MD:BCMA testing—the NIH [National Institutes of Health] actually does it. There are some data, and we are still getting the data in as we talk. The main thing that we have noticed is that not many patients actually have very high-level expression. We don’t really know whether those patients will respond to therapy. It’s like CD30, right? The expression level may correlate, but it’s not a complete absolute correlation, in terms of using the antibody against the particular target. So in terms of the cutoff, of whether 50% expression is necessary or not, I don’t think there’s a clear answer.

Ajai Chari, MD:Like in the preliminary work, I do think that there’s a lot of variability in BCMA testing as well.

Pei Lin, MD:Exactly.

Ajai Chari, MD:Because of the antibody quality.

Pei Lin, MD:Right. So the data are still coming out.

C. Ola Landgren, MD, PhD:The new clinical trials that focus on BCMA and CAR T-cell therapy don’t require BCMA testing at all. There are data from several groups that say that if you look in patients carefully, you will see BCMA expression in every patient. It may be low in some patients, but at least there is some expression. Many of these emerging studies, as you indicate, suggest that even with lower expression levels, you have a very strong efficacy from these therapies. So the jury is still out—to see how the correlation for duration of response goes. We don’t really know that.

Transcript edited for clarity.