Novel and Cellular Therapies to Treat Patients With R/R Multiple Myeloma

At the 2023 Great Debates & Updates in Hematologic Malignancies conference in New York, New York, Saad Z. Usmani, MD, MBA, FACP, Memorial Sloan Kettering Cancer Center, New York, New York, discussed novel and cellular therapies used to treat relapsed/refractory multiple myeloma, including but not limited to dual CAR-T therapies. 

Transcript: 

Hello. My name is Saad Usmani and I'm the chief of the Myeloma Service at the Memorial Sloan Kettering Cancer Center in New York City. I'm here at the Great Debates [& Updates meeting] in New York. I spoke about novel and cellular therapies in 2023, things that are coming down the pike beyond what’s commercially available. I covered cellular therapies including novel BCMA CAR T-cell therapies, as well as BCMA CAR combined with CV19—so, dual CAR T strategy. 

I also talked about GPRC5D CARs that were originally developed at MSK, published by my colleague, Sham Mailankody, and are now being commercially developed by BMS. Some of that early data that was presented at ASH 2022 showing very high response rates in patients, 100% response rate in non-BCM exposed patients, and well over 70% response rates in BCM exposed patients.

These kinds of overall responses are kind of unprecedented in myeloma, knowing where we came from, and where therapies were being approved at 20 to 30% response rates just 8 or 9 years ago. There are very encouraging results with these cellular therapies. 

Then, I talked about various BCMA bio-specific platforms that target BCMA, as well as GPRC5D and FCRH5. I shared data around the responses, the cytokine release syndrome, as well as the infection risk with these bio-specifics. 

I also discussed the potential role of these therapies, not just in the relapse setting, but even in earlier lines of treatment. I discussed the potential mechanisms of resistance, which could be due to overexpression of checkpoint inhibition, checkpoints essentially. As well as increased T-REGs and CD4 cells, and increased MDSCs that influence lack of response to T-cell directed therapies. 

I switched gears a little bit, starting to talk about some of the small molecule combinations with selinexor cell mods, including some iberdomide and mezigdomide data showing good promise in more relapsed/refractory multiple myeloma.

I talked about the immune cytokine therapy or class of therapies now emerging with Modakafusp alfa, which is a CD38-directed treatment delivering interferon to the myeloma cells, showing response rates of about 40 to 50% depending on whether patients have been BCMA or non-BCMA exposed in the relapse space. A lot of therapies are showing very high response rates in these patients. Many of these therapies have already started to combine themselves with other existing myeloma treatments and starting to move into the earlier lines of treatment. 

The last section of my talk was focused on disparities in healthcare in myeloma when it comes to minorities, specifically Black American myeloma patients. Highlighting the fact that access to care as well as to CAR T-cell therapy has been an issue. There's always an issue of awareness about this disease within the population at large, as well as within the Black American population.

I highlighted some of the culturally sensitive conversations that can be had to overcome these disparities. I highlighted the lack of clinical trial participation that we have from minorities, and how we are starting to mitigate that by being more inclusive in our clinical trial criteria, such as lowering the white blood cell count or neutrophil count requirement and being a little bit more generous with the renal insufficiency requirements, et cetera.

Overall, I had a lot of data to discuss in the time allotted to me. It was a very robust discussion with the panel and the Q&A as well.

Source:

Usmani, S. Relapsed/refractory multiple myeloma: Novel and cellular therapies in 2023. Presented at Great Debates & Updates in Hematologic Malignancies Conference; April 13-15, 2023; New York, NY.