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Chimeric antigen receptor (CAR) T-cell therapy, an advanced therapy medicinal product, is regulated by the European Medicines Agency (EMA) as well as other federal and regional authorities.1 All products must adhere to the good manufacturing practice standards, defined as potent products manufactured safely according to standardized methods under closely controlled, reproducible, and auditable conditions.1
Historically, BioPharma has supplied the majority of CAR T-cell products; however, several academic centers have recently developed point-of-care manufacturing capabilities with the aim of improving patient access and streamlining costs.1
Two CAR T-cell products have been recently developed in academic settings, and pilot studies for each have evaluated the safety and efficacy of these potential therapies. The first product, ARI0002h, was investigated in the pilot CARTBCMA-HCB-01 study (NCT04309981) by Caldes et al.2 The second product, HBI0101, was evaluated in a phase I study (NCT04720313) by Asherie et al.3 Here, we summarize the key results from both trials.
This was a single-arm multicenter, open-label pilot study. The eligibility criteria, dosing schedule, and study endpoints were reported previously by the Multiple Myeloma Hub.
A total of 30 patients with relapsed/refractory multiple myeloma received a CAR T-cell infusion, and their baseline characteristics are shown in Table 1.
Table 1. Baseline patient characteristics*
Characteristic, % (unless otherwise stated) |
N = 30 |
---|---|
Age, years |
61 |
Sex |
|
Male |
60 |
Female |
40 |
Median time since diagnosis, years |
4.7 |
ISS stage |
|
I |
20 |
II |
32 |
III |
48 |
ECOG Performance Status |
|
0 |
62 |
1 |
31 |
2 |
7 |
High-risk cytogenetics |
33 |
TP53 alterations |
23 |
t(4;14) |
13 |
t(14;16) |
3 |
Previous lines of therapy |
|
Triple exposed |
100 |
Triple refractory |
67 |
Penta exposed |
37 |
Penta refractory |
23 |
Refractory to the last line |
100 |
ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System. |
Figure 1. Patient response rates in the first 100 days after ARI0002h infusion*
CR, complete response; ORR, overall response rate; PR, partial response; VGPR, very good partial response.
*Adapted from Caldes, et al.2
Table 2. Response rates from the post hoc analysis*
Response, % |
N = 30 |
---|---|
Overall response |
100 |
Complete response |
67 |
Very good partial response |
27 |
Partial response |
7 |
*Adapted from Caldes, et al.2 |
Table 3. All Grade ≥3 adverse events*
Adverse event (%) |
N = 30 |
---|---|
Anemia |
10 |
Neutropenia |
70 |
Thrombocytopenia |
47 |
Pyrexia |
7 |
Lymphocytosis |
3 |
Lymphopenia |
3 |
Febrile neutropenia |
3 |
Diarrhea |
3 |
Alanine aminotransferase increased |
3 |
Aspartate aminotransferase increased |
3 |
Leishmaniasis |
3 |
Rhinovirus infection |
3 |
Septic shock |
3 |
Severe acute respiratory syndrome |
3 |
Staphylococcal bacteremia |
3 |
COVID-19 |
3 |
Head injury |
3 |
Seizure |
3 |
Acute kidney injury |
3 |
*Adapted from Caldes, et al.2 |
This was a single-center, phase I study. The eligibility criteria, dosing schedule, and study endpoints are shown in Figure 2.
Figure 2. Eligibility criteria, dosing schedule, and study endpoints*
ECOG, Eastern Cooperative Oncology Group; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; RRMM, relapsed/refractory multiple myeloma.
*Adapted from Asherie, et al.3
A total of 20 patients with relapsed/refractory multiple myeloma received a CAR T-cell infusion. Baseline characteristics are shown in Table 4.
Table 4. Baseline patient characteristics*
Characteristic, % (unless otherwise stated) |
N = 20 |
---|---|
Median age, years |
62 |
Sex |
|
Male |
40 |
Female |
60 |
Median time since diagnosis, months |
55 |
R-ISS |
|
I |
5 |
II |
55 |
III |
10 |
ECOG Performance Status |
|
0 |
35 |
1 |
20 |
2 |
45 |
Cytogenetic abnormalities |
|
High risk |
50 |
Standard risk |
60 |
Unknown |
5 |
Median previous lines of therapy, n |
6 |
ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System. |
Figure 3. Response rates for patients treated with HBI0101*
CR, complete response; sCR, stringent complete response; MRD, measurable residual disease; ORR, overall response rate; VGPR, very good partial response.
*Adapted from Asherie, et al.3
Table 5. All Grade 3 and 4 adverse events*
Adverse event, % |
N = 20 |
---|---|
Hematologic ≤28 days |
|
Neutropenia |
100 |
Thrombocytopenia |
60 |
Anemia |
65 |
Lymphopenia |
100 |
Febrile neutropenia |
75 |
Hematologic >28 days |
|
Neutropenia |
30 |
Thrombocytopenia |
35 |
Lymphopenia |
30 |
Hypogammaglobulinemia |
25 |
Other ≤28 days |
|
Elevated liver enzymes |
10 |
Sepsis |
15 |
Infectious gastroenteritis |
5 |
Pulmonary edema |
5 |
Other >28 days |
|
Atrial fibrillation |
5 |
Pulmonary edema |
5 |
Elevated liver enzymes |
5 |
Pulmonary embolism |
5 |
*Adapted from Asherie et al.3 |
CRS of any grade was experienced by 90% of patients. The median duration was 2 days, and there were no Grade ≥3 events; however, a higher rate of Grade 2 CRS was noted in Cohorts 3 and 2 compared with Cohort 1 (Figure 4).
Figure 4. Rate of CRS in Cohorts 1, 2, and 3*
*Adapted from Asherie, et al.3
Overall, both products demonstrated deep and sustained responses in patients with heavily relapsed or refractory multiple myeloma. Both the response rates and safety results were in line with those of currently approved therapies, as well as results reported in the literature. However, the relatively short median follow-up time of 136 days from the first study was cited as a limitation, as well as a small sample size; this led to wide 95% CIs in the second study. While access to CAR T-cell therapy remains limited due to logistical and financial constraints, these two academically developed products highlight the potential in broadening access for patients by offering reduced vein-to-vein time, greater manageability, and reduced financial burden, while simultaneously testifying to the capability of academic institutions in producing this advanced medicinal technology. The requirement of local current good manufacturing practice facilities and trained staff remains an overall barrier; however, the introduction of semi-automated manufacturing platforms has the potential to standardize the process across multiple sites.
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