In patients with heavily pretreated relapsed or refractory multiple myeloma (R/R MM) with aggressive disease, the T-Charge manufactured chimeric antigen receptor (CAR) T-cell therapy PHE885 produced high response rates with no unexpected safety findings. Adam Samuel Sperling, MD, PhD, of Dana-Farber Cancer Institute in Boston, explained that the PHE885 cells expanded rapidly and demonstrated durable persistence in vivo. He presented the updated study results at the American Society of Clinical Oncology (ASCO) Annual Meeting June 3 and noted that, since conversion to complete response/stringent complete response has occurred as late as 18 months after infusion, longer follow-up is ongoing to identify a recommended dose for future development.
The phase I study included 50 patients with a median age at enrollment of 65 years (range = 45-81) and a median prior lines of treatment of four (range = 2-10). Approximately 33% of patients had extramedullary disease and the vast majority (94%) were triple refractory. The patients received differing amounts of CAR T cells: four received 2.5 million, 13 received 5 million, 20 received 10 million, one received 14.3 million, and 11 received 20 million. For most patients (61%), PHE885 was manufactured in a single institution and these patients proceeded from apheresis to lymphodepletion in a median of 17 days. The median follow-up was 6.7 months for all dose levels and the median time for last detectable transgene was six months. All but one patient responded to therapy.
Dr. Sperling explained that a unique aspect of the product is that manufacturing is done in less than 48 hours. This stands in marked contrast to currently available products that require 10 to 14 days to manufacture. This standard two-week manufacturing time can translate into a six- to eight-weeks wait time for treatment. “A lot of patients can’t wait six to eight weeks for those treatments because their disease is too aggressive,” said Dr. Sperling. In contrast, he noted, patients in the study were able to receive treatment with PHE885 in two to three weeks.
The abbreviated manufacturing time also means the cells spend less time in an artificial culture media and the resulting product had a “more naïve or stem-like phenotype for the T cells,” said Dr. Sperling. In addition, while other products, such as idecabtagene vicleucel (ide-cel), typically infuse on the order of 450 million cells, the treatment protocol for PHE885 calls for infusion of 10 to 20 million cells. The PHE885 cells then expand in the patient, a process which Dr. Sperling anticipates will be more beneficial to the patient than receiving cells that have been expanded in culture. In particular, he said that, for the patients who relapse, the healthier T cells may function better and last longer. He acknowledged, however, that the follow-up on the study is still not long enough to determine if this is true.
The phase II trial (NCT05172596) has been enrolling in Europe and elsewhere in the world and just began enrollment in the U.S. The target dose for the phase II PHE885 trial is 10 million cells and patients will be followed for acute and intermediate safety and efficacy within this trial for a minimum of two years before being transferred to the long-term follow-up trial. The primary outcome measure is overall response rate.
Any conflicts of interest declared by the authors can be found in the publication. Some of the data reported here were updated at the time of presentation and differ from that reported in the abstract.
Reference
Sperling AS, Derman BA, Nikiforow S, et al. Updated phase I study results of PHE885, a T-Charge manufactured BCMA-directed CAR-T cell therapy, for patients (pts) with r/r multiple myeloma (RRMM). Abstract 8004. Presented at the 2023 American Society of Clinical Oncology; June 3, 2023; Chicago, Illinois.
