Mounzer Agha, MD

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spoke with Mounzer Agha, MD, of the University of Pittsburgh School of Medicine Hillman Cancer Center, about the encouraging safety profile reported from the 

 trial investigating ciltacabtagene autoleucel (cilta-cel) for patients with previously treated multiple myeloma at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

The strategies he detailed included reducing neurologic adverse events by use of more effective bridging therapy, frequent assessment of CAR T-cell–related immune effector cell-associated neurotoxicity syndrome, and handwriting assignments to detectmicrographia, among others.

The most important thing I’d really like to emphasize is that in CARTITUDE-2, we showed an excellent safety profile.

 where we encountered the cognitive and neuro-movement disorders, we [do] not seen that now anymore because we applied the mitigation strategies. By eliminating that, it opens the door to apply this treatment in earlier treatment settings.

1. Agha ME, Cohen AD, Madduri D, et al. CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy. 

 2021;39(suppl 15):8013. doi:10.1200/JCO.2021.39.15_suppl.8013
2. Einsele H, Parekh SS, Madduri D, et al. Incidence, mitigation, and management of neurologic adverse events in patients with multiple myeloma (MM) treated with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-2. 

 2021;39(suppl 15):8028. doi:10.1200/JCO.2021.39.15_suppl.8028
3. Usmani SZ, Berdeja JG, Madduri D, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1. 

 2021,39(suppl 15; abstr 8005). doi:10.1200/JCO.2021.39.15_suppl.8005

Videos

The director of the Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center discussed strategies to manage AEs associated with CAR T therapy.

Mitigating Adverse Events in CAR T-Cell Therapy: Mounzer Agha, MD

spoke with Mounzer Agha, MD, University of Pittsburgh School of Medicine Hillman Cancer Center, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting about the value of the conference for multiple myeloma. He detailed the importance of investigators converging to discuss the future of treatment across tumor types.

ASCO, along with [the American Society of Hematology Annual Meeting] and the European Hematology Association [Congress], is a representative benchmark where we really set the foundation for what’s to come in the next year and the years to come. What we hope to accomplish at this ASCO is to set the foundation for treatments that were [once] viewed as applicable only for last-line therapy [and apply them to] earlier treatment settings safely. In the field of multiple myeloma, we are still discussing the role of high-dose melphalan in autologous stem cell transplant. This role has gone unchallenged now for a couple of decades and if you really think about it, it is not a curative treatment. It does lead to an improvement in survival and disease control, but it does not represent a long-term solution for patients with multiple myeloma. CAR T[-cell therapy] offers the hope of long-term disease control and perhaps cure in a subset of patients [with multiple myeloma]. What we demonstrate this time is that you can offer this treatment effectively and safely. This represents a paradigm shift and ASCO is the venue that we would like to disseminate this to the public and to other physicians.

Agha ME, Cohen AD, Madduri D, et al. CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy. 

 2021;39(suppl 15):8013. doi:10.1200/JCO.2021.39.15_suppl.8013

The director of the Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center discussed how the meeting sets the foundation for what’s to come in the treatment of multiple myeloma and other hematologic malignancies.

Setting a Foundation for CAR T-Cell Therapy: Mounzer Agha, MD

The phase 2 CARTITUDE-2 trial (NCT04133636) evaluated ciltacabtagene autoleucel (cilta-cel) in patients with multiple myeloma and found it to be a well-tolerated and efficacious therapy. 

spoke with Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center and the clinical director of the Hematopoietic Stem Cell Transplantation of UPMC to learn more about the trial.

Agha's key takeaway from CARTITUDE-2 is that B-cell maturation antigen chimeric antigen receptor (CAR) T-cell therapy is extremely effective in patients with multiple myeloma and can be used safely in this population. The adverse event profile of cilta-cel, including neurotoxicity and cytokine release syndrome (CRS), was manageable. The majority of patients who experienced CRS had grade 1 or 2 toxicity and most had quick resolution of this event.

The movement and neurocognitive events observed in CARTITUDE-1 (NCT03548207) were not encountered in CARTITUDE-2 because the risk factors were identified by the investigators, according to Agha. They started a mitigation strategy which allowed options such as a bridge in therapy and aggressive treatment of CRS. By doing so, neurocognitive and movement toxicities were less likely.

Cilta-cel has shown to be an effective and safe therapy for patients with multiple myeloma in earlier treatment settings. Agha feels this represents a paradigm shift in the treatment of multiple myeloma, and patients will not have to progress on multiple other therapies before receiving CAR T-cell therapy. Five years from now, he is confident CAR T will be a first-line therapy.

The director of the Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center discussed the phase 2 CARTITUDE-2 trial.

CAR T-Cell Therapy's Future in Multiple Myeloma: Mounzer Agha, MD

CancerNetwork® spoke with Mounzer Agha, MD, UPMC Hillman Cancer Center, to learn more about findings from the phase 2 CARTITUDE-2 trial (NCT04133636) and how the investigation of ciltacabtagene autoleucel (cilta-cel) in patients with multiple myeloma compares with data from CARTITUDE-1.

CARTITUDE-1 [NCT03548207] showed [extreme] treatment efficacy. Here, we show that the treatment is equally effective and actually quite superior. As you can see from the results that we presented, we have taken patients with 1 to 3 [prior] lines of therapy. If you look at the patient characteristics, they were [mostly] triple-class refractory. Sixty-five percent of the patients were triple-class exposed and 20% were refractory; 40% of patients were penta-drug exposed and 5% were refractory. Sixty percent of patients were refractory to daratumumab [Darzalex] and 85% of the patients had prior autologous stem cell transplant. Although we moved this to an earlier line of therapy, the majority of the patients were refractory to first-line therapy. Ninety-five percent of them were refractory, and 95% of them were exposed to alkylating agents.

Despite that, the overall response was very impressive at 95%. Seventy-five percent were in complete remission and 45% of those were stringent complete remissions. The goal was to see the [minimal residual disease (MRD)] negativity at 10-5. Of all the patients that were MRD valuable at 10-5 at the time of data cutoff, they were all negative. This is very impressive. It’s showing that you have a very high response rate. The responses continue to deepen over time, although we only have a 5.8-month follow-up, but the responses are still ongoing. The point of maximum response we saw on a prior study in CARTITUDE-1 was 9 months. We’re not even there and despite that, we still see an ongoing response rate.

This is extremely encouraging. It actually represents a paradigm shift in the treatment of multiple myeloma. Now we’ve shown for the first time that rather than waiting to apply this very effective therapy in advanced disease, we can start [treating] patients earlier in their disease setting as soon as they show refractoriness to standard therapy.

 2021;39(suppl 15):8013. doi:10.1200/JCO.2021.39.15_suppl.8013
2. Usmani SZ, Berdeja JG, Madduri D, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1. 

 2021,39(suppl 15).8005. doi:10.1200/JCO.2021.39.15_suppl.8005

The director of the Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center discussed findings from the CARTITUDE studies.

Mounzer Agha, MD

Articles

Mitigating Adverse Events in CAR T-Cell Therapy: Mounzer Agha, MD

Setting a Foundation for CAR T-Cell Therapy: Mounzer Agha, MD

CAR T-Cell Therapy's Future in Multiple Myeloma: Mounzer Agha, MD

Cilta-cel for the Treatment of Multiple Myeloma: Mounzer Agha, MD