CAR-T Meeting 2021 | Clinical advances with CAR-Ts and bispecifics in R/R myeloma
Maria-Victoria Mateos, MD, PhD, University of Salamanca, Salamanca, Spain, gives an overview of the recent clinical advances with CAR T-cells and bispecifics in relapsed/refractory (R/R) multiple myeloma. Over the past decade, new treatments have transformed survival outcomes of myeloma. However, patients with myeloma refractory to the therapies that currently comprise the hematologic standard of care, including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies, have limited treatment options. It is expected that additional agents will be available for triple-refractory disease soon. Dr Mateos highlights idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), both BCMA-targeting CAR T-cells. Various bispecific monoclonal antibodies targeting BCMA are currently in development, with promising results. This interview took place during the 3rd European CAR T-cell Meeting.
Transcript (edited for clarity)
Hello to everyone, and I will address how might we identify the most appropriate cellular therapy for patients with multiple myeloma. And we know that when we face with relapse and refractory myeloma patients already exposed to proteasome inhibitors, IMiDs, and anti-CD38 monoclonal antibodies, the outcome is really very poor. And this population represents an unmet medical need.
BCMA targeted therapy, emerged as a new possibility for these patients and we can go through a BCMA targeted therapy utilized in the different approaches...
Hello to everyone, and I will address how might we identify the most appropriate cellular therapy for patients with multiple myeloma. And we know that when we face with relapse and refractory myeloma patients already exposed to proteasome inhibitors, IMiDs, and anti-CD38 monoclonal antibodies, the outcome is really very poor. And this population represents an unmet medical need.
BCMA targeted therapy, emerged as a new possibility for these patients and we can go through a BCMA targeted therapy utilized in the different approaches. It is possible to utilize antibody-drug conjugates and belantamab mafodotin has been so far approved for relapse and refractory myeloma patients after four therapies, including PIs, IMiDs and anti-CD38 monoclonal antibodies and belamaf is effective in these triple-class refractory myeloma patients with response rate of approximately 30%. But important to note that the medium duration of the responses of approximately one year, and we have to consider the keratopathy as well as the thrombocytopenia has the most relevant side effects. Together with this antibody-drug conjugate that we can target a BCMA in this triple-drug-class refractory myeloma patients through the BCMA CAR T-cells. And this possibility… This option of therapy is something new, but with promising relapse in this population. We have results coming from ide-cel, a Phase II pivotal clinical trial conducted basically in relapse and refractory myeloma patients.
The overall response rate is almost 80% with a medium progression survival of approximately nine months. And, definitely these results indicate that the BCMA CAR T-cell covered the unmet medical need. And cilta-cel, another BCMA CAR-T is also resulting in very promising efficacy results. So with the over 90% of overall response rate and complete response rate of approximately 70%. From the toxicity point of view, we have to remark the cytokine release syndrome present in almost all patients as well as neurotoxicity and cytopenias. And we have to take care of infections. These are two BCMA CAR T-cells, cilta-cel and ide-cel, will be available hopefully very soon in the clinic and other new BCMA targeted CAR T-cells that are coming in different clinical trials and together with the CAR T-cells and the bispecific, we have the bispecific monoclonal antibodies, And there is I would say our long list of different BCMA bispecific monoclonal antibodies resulting also quite effective in these triple-drug-class refractory population. With the overall response rates ranging from 70 to 80%, but data are much more immature at this moment. And we don’t have any data in terms of durability of the response. And from the safety point of view, we have to consider cytokine release syndrome as well as a negative toxicity. But I will say that these side effects are less frequently reported in comparison with the BCMA CAR-Ts.
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