Multiple Myeloma: Use of Bispecifics in Challenging Patient Populations
Before closing out their program on bispecifics in multiple myeloma, expert oncologists consider the value of these agents in more challenging patient populations.
Transcript:
Amrita Krishnan, MD: Let’s talk about challenging populations too. Philippe alluded a bit to this with the teclistamab data in terms of patients with extramedullary disease [EMD], but it’s not unique to teclistamab. It’s a challenge we have with bispecifics. What has people’s experience been, and how would you approach patients with a significant amount of extramedullary disease, which is common in the relapsed setting?
Josh Richter, MD:I’ll throw this out, and again these are extraordinarily early data, but it turns out that there are some data in Korea and parts of Europe that are combining teclistamab and talquetamab. And some of their early data show that EMD seems to be a bit more ameliorated when you combine these two. There are a whole host of issues when you start combining teclistamab and talquetamab, but it would not surprise me if that becomes one of the options to consider in the future.
Alfred Garfall, MD: I would also think about combining with radiation as well. Even in patients with extramedullary disease, while that EMD may be resistant, patients getting teclistamab with EMD will still have this exquisite effect in the bone marrow. If you can combine targeted radiation for a couple of isolated areas of clinically significant extramedullary disease, combined with good immune surveillance of the non-EMD components, maybe you can prevent EMD relapse by giving teclistamab after radiation for isolated areas of extramedullary disease. That’s not something that’s been prospectively studied, but it is an appealing approach that I’ve considered in some patients we’ve been treating with the commercially available product, and even some patients from our experience who have had EMD coming on the study and didn’t respond, but got radiation to that EMD on the study.
Amrita Krishnan, MD: Speaking of commercial availability, in regard to renal insufficiency, as we know most of those patients are excluded from the trials. What would people’s level of comfort be about treating those patients with these agents?
Alfred Garfall, MD: A high level of comfort in my opinion. This is a distinguishing feature with CAR [chimeric antigen receptor] T-cell therapy. We’ve had reports of CAR T cells being given to patients with renal insufficiency, and I agree it’s feasible, but there is always some question about fludarabine dosing in renal insufficiency and the general fragility of that population if they go through hemodynamic changes during CRS [cytokine release syndrome]. We’ve treated several patients with moderate to severe renal impairment, and I can’t think mechanistically, except maybe a slightly increased risk of tumor lysis syndrome and complications there. But this is a mechanism of action that should be compatible with advanced renal impairment, which is an enormous problem in our patient population. I hope there are some prospective studies looking at this, and maybe some will lead to more permissive inclusion criteria in the clinical trials going forward with drugs with this mechanism of action.
Philippe Moreau, MD:I agree. I think that’s feasible to use those agents in patients with severe renal impairment, and maybe we have to be careful with the risk of CRS in this setting. In the case of grade 3 CRS, potentially the patient could be on dialysis following the administration. But since we have few cases of grade 3 CRS, almost 1% to 2%, I think we can use safely those agents in patients with severe renal impairment.
Amrita Krishnan, MD: Thank you all for a very informative hour. I hope this is helpful to our audience. We may have raised more questions than we answered, and at least some of this is more opinion based, but is based on the data we have available right now. Again, I thank you all for your time.
Transcript edited for clarity.
