Janssen, a pharmaceutical company of the group Johnson & Johnson, announced the long-term results of the CARTITUDE-1 phase 1b / 2 study evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), an investigational CAR-T therapy for the treatment of patients with relapsed or refractory multiple myeloma. The data, presented at the American Society of Haematology (ASH) 2021 annual meeting and selected in the Highlights of the ASH program, showed how a single infusion of Cilta-cel, based on T lymphocytes engineered to express a chimeric receptor for the antigen (CAR-T) directed towards BCMA (B lymphocyte maturation antigen), induces a deep and lasting response, with a high overall response rate (ORR) of 98 percent.
I study
In the 97 patients treated with cilta-cel, the overall response rate (ORR) was 98 percent and improved over time, reaching a stringent complete response in 83 percent of patients at a median follow-up. of 22 months. This value is greater than that of 80 percent achieved at a median follow-up of 18 months presented at the last American Society of Clinical Oncology (ASCO) meeting and compared to that of 67 percent at a median follow-up. 12.4 months presented at the ASH 2020 congress. At a median follow-up of 22 months, progression-free survival (PFS) and median overall survival (OS) have not yet been achieved, suggesting a long-term duration patient responses and survival. The two-year rates of PFS and OS were 61 percent (95 percent confidence interval CI, 48.5-70.4) and 74 percent (95 percent CI – 61.9 – 82, respectively. , 7). In 61 patients, minimal residual disease (MRD) was assessed: among them, 92 percent reached negativity (sensitivity threshold of 10–). Patients who achieved minimal residual disease negativity and maintained it for 6 and 12 months or more showed 2-year PFS rates of 91 percent, respectively (95 percent CI, 67.1 – 97.8) and 100 percent.
“Unfortunately, multiple myeloma patients exposed to at least three treatment regimens have lost their efficacy and have a median survival of less than one year with currently available treatments.Said Thomas Martin, MD*, Director of Clinical Research, Clinical Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program, Associate Director, Myeloma Program and Co-Leader, Hematopoietic Malignancies Program, at UCSF Helen Diller Family Comprehensive Cancer Center sperimentatore principale dello studio. “New data from the CARTITUDE-1 study reinforce previous findings, showing that a single infusion of cilta-cel results in lasting responses and improves survival in the study population, further confirming cilta-cel’s potential to offer a viable new option. therapy for patients and doctors.”
The median time to first response was one month (range, 0.9 – 10.7), with increasingly profound responses over time. In addition, the median time to best response was 2.6 months (range, 0.9 – 17.8), while the median time to complete response or best responses was 2.9 months (range, , 0.9 – 17.8). Twelve percent of patients achieved a very good partial response, while 3 percent achieved a partial response. The study included patients who had previously received a mean of six treatment regimens (range, 3-18). All patients were triple-exposed (immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) 42 percent of them were penta-refractory and 99 percent were refractory to the last line of treatment.
“These data add to the large body of evidence supporting the potential clinical benefit of cilta-cel in the treatment of patients with relapsed or refractory multiple myeloma, a population in need of new therapeutic options.,” ha dichiarato Sen Zhuanh, M.D., Ph.D., Vice President, Clinical Research and Development, Janssen Research & Development, LLC. “We are awaiting further evaluations of cilta-cel as part of our CARTITUDE global clinical development program which also includes study in patients with first diagnosed multiple myeloma.”
Data in detail
The data show an online safety profile for cilta-cel, where no new safety signals were observed with longer follow-up. In the 18-month follow-up presented at the 2021 ASCO congress, the most frequent haematological adverse events (AEs) were neutropenia (96 percent), anemia (81 percent), thrombocytopenia (79 percent), leukopenia (62 percent). ) and lymphopenia (53 percent). At 18 months, cytokine release syndrome (CRS) of any grade was observed in 95 percent of patients with a median duration of four days (range, 1-97) and in 99 percent of cases it resolved by 14 days from the appearance. Of the 92 patients with CRS at 18-month follow-up, 95 percent were grade 1/2. Any grade neurotoxicity was observed in 21 percent (n = 20) of patients, with grade 3 or higher levels in 10 percent (n = 10) of patients. There were no additional cilta-cel-related neurotoxicity events, nor were motor-neurocognitive (MNT) adverse events reported in CARTITUDE-1 after those shown at the ASH 2020 congress at median follow-up of 12.4 months. At the 22-month data cut-off, cilta-cel therapy was administered to over 200 patients under the CARTITUDE clinical development program and the incidence of MNT decreased to less than 1 percent after implementation of prevention measures for MNT events.
“We are pleased to be able to present again, at a long-term follow-up, this time of almost two years, the data of this innovative treatment, aimed at patients with relapsed or refractory multiple myeloma “ ha dichiarato Edmond Chan MBChB MD (Res), EMEA Therapeutic Area Lead Haematology, Janssen – Cilag Limited. “The prolonged efficacy and safety profile in line with this therapy are based on solid results seen to date and may represent a step forward in changing the expectations of patients facing a multiple myeloma diagnosis.”
Phase 1b / 2 subgroup analysis of the CARTITUDE-1 study
The other data presented at the 2021 ASH congress (Abstract # 3938) demonstrate that cilta-cel resulted in deep and lasting responses in all subgroups analyzed within the CARTITUDE-1 study, at a median follow-up of 18 months.4 An overall response rate (ORR) of 95 to 100 percent was observed in patients in each subgroup, including those with high-risk cytogenetics, ISS stage III multiple myeloma, baseline bone marrow plasma cells ≥ 60 per one hundred and presence of plasmacytomas at baseline. In ISS stage III patients with high-risk cytogenetics and baseline plasmacytomas, the median duration of response was shorter, as were median progression-free survival (PFS) and overall survival (OS) at 18 months. The safety profile of cilta-cel in all subgroups was consistent with the overall population, with no new safety signals found.
Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell, the plasma cells found in the bone marrow. When these cells are damaged, they proliferate rapidly and cause normal bone marrow cells to be replaced by cancer cells. In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020 and more than 32,500 patients died.
While some patients with multiple myeloma do not have any symptoms, most are diagnosed precisely because of the symptoms which can include bone fractures or pain, reduced red blood cells, fatigue, increased calcium levels, kidney problems or infections.