According to a recent report in Cancer Network, the results from CARTITUDE-1 were well received. CARTITUDE-1 is a phase 1b/2 clinical trial of the CAR T-cell treatment, Cilta-Cel, for the treatment of relapsed and refractory (treatment-resistant) multiple myeloma patients.
The primary objectives of the study’s phase 1b were to evaluate the safety of Cilta-Cel (ciltacabtagene autoleucel) and to establish a recommended dose for phase 2.
The phase 2 portion of the study determined the efficacy of Cilta-Cel in accordance with the Objective Response rate (ORR).
About the Study
The study’s impressive results were set forth at the Annual 2020 Meeting of the American Society of Hematology (ASH). The ORR was 96.9% which consists of 67% of participants having a complete response, 25.8% of patients showing a partial response rated as “very good,” and lesser “partial” responses of 4.1%. The median time to the initial response was one month with a range of 0.9 to 8.5.
The drug was administered at the recommended dose. Results of the safety profile were satisfactory.
The median age was 61 within a range of 43 to 78. The patient cohort consisted of 89.7% who had undergone autologous (from the patient’s body) stem cell transplants. A total of 8.2% of trial participants received allogenic transplants which involve the transfer of stem cells from a healthy donor to the patient. Both types of transplants require high-intensity chemotherapy prior to the transfer.
About the ASH 2020 Presentation
During her presentation at the 2020 ASH meeting, Dr. Deepu Madduri, assistant professor of hematology at Mount Sinai in New York, described the response rate from the 97 heavily pre-treated patients as being “exceptional” in that the responses were early and durable. Dr. Deepu added that the responses were achieved with a one-time therapy.
She explained that myeloma patients who have relapsed or are refractory have a 9.2 month overall survival. That number is much smaller for patients who have refractory disease.
However, Dr. Deepu said that the CARTITUDE-1 study has already passed the one-year mark with a majority of study participants still progression-free.
About Adverse Events (AEs)
Hematologic events occurred in ninety-nine percent of the trial patients. The grade three or four AEs that were most common were neutropenia, leukopenia, anemia, and thrombocytopenia (low platelets).
Grade three or four non-hematologic toxicities were uncommon in this study.
About Cytokine Release Syndrome (CRS)
The cytokine release syndrome (CRS) is an AE typically associated with CAR t-cell therapy. CRS occurred in 94.8% of study participants. However, only 4.1% were found to be at higher grade three or four levels.
With respect to CRS, corticosteroid support was required in 21.6% of study participants and tocilizumab was needed for 69.1% of patients. Within fourteen days of onset, symptoms of CRS were resolved in 98.9% of patients.
Neurotoxicity is another CAR t-cell complication. It was found at most grade levels in 20.6% of all study participants. Grade >3 neurotoxicities were found in 10.3% of patients.
About Neurotoxicity
Neurotoxicity is defined as the degree to which the nervous system is damaged by a substance such as a therapeutic agent. It is a well-known complication of CAR T-cell therapies.
Neurotoxicity was reported in the CARTITUDE-1 study to have affected 20.6% of patients in total and 10.3% of patients at grade >3. The majority of neurotoxicity complications were resolved within four days on average within a range of one to twelve days.
There were other reported neurotoxicities in twelve patients that surfaced even after the CRS (cytokine release syndrome), but they had all been resolved.
- Five patients had neurocognitive changes that may have involved the central nervous system;
- Six of the remaining seven patients who developed peripheral motor neuropathy or nerve palsy reported that their issues had been resolved.
Deaths During the Study
Fourteen patients died within 45 to 694 days after the Cilta-Cel infusion. Five patients succumbed to progressive disease. Three patients experienced AEs that were not related to the therapy. However, six deaths were acknowledged as AEs related to Cilta-Cel treatment. The list included but was not limited to, sepsis, neurotoxicity, respiratory failure, and lung abscess.
Taking these AEs into account, the CARTITUDE team developed a program that allowed more chemotherapy and aggressive steroids as well as earlier intervention and expanded monitoring.
In accordance with earlier CARTITUDE-1 results, the FDA granted Cilta-Cel Breakthrough Therapy Designation to expedite the development of the drug.
