Non-Western Real-World Experience of Axi-Cel CAR-T in Refractory/Relapsed B-Cell Lymphoma from a Tertiary Center in Saudi Arabia
Authors: Alsuhaibani Khalid , Hejab Amal , Ahmed Syed Osman , Alahmari Ali , Hanbali Amr , Rasheed Walid , Alshaibani Alfadel , Chaudhri Naeem A. , Saad Ayman , Alotaibi Shaykhah , Alkhaldi Hanan , Alamer Abdullah , Alfayez Mansour , Alhayli Saud , Shaheen Marwan , Alfraih Feras Abdulaziz , Alotaibi Ahmad S. , Samarkandi Hadeel , Syed Farhatullah , Alsharif Fahad , Almohareb Fahad , Alzahrani Hazza , Aljurf Mahmoud , Elfakih Riad , Albabtain Abdulwahab 
Published: December 2024

The access to Anti CD-19 CAR-T cell in the treatment of malignancies increased over the past years. Thus, the need to bring real-world evidence on the efficacy and toxicity of this important treatment modality increases, especially from ethnicities who are likely to be under-represented in registrational clinical trials.
This is the first report of Axi-cel outcomes from Saudi Arabia. We retrospectively looked at the data of the first 50 patients who were treated with Axi-cel during the period between February 2023 to April 2024 in King Faisal Specialist Hospital and Research Center, Riyadh, SA.
A total of 50 pts received Axi-cel for refractory/relapsed B-cell lymphomas, 38% (n=19) as a second line (2nd line group), while 62% (n=31) received it as a third line or beyond (3rd line or beyond group) with median lines of 3 (range 3-5). The median age was 53 years (range 17-78). All patients were of Arab ethnicity, of whom 60% (n=30) were males. The median length of inpatient stay was 26 days (range 17-147). Regarding performance status, 86% (n=43) had an ECOG score of one or less. The majority of pts, 80% (n=40) had diffuse large B-cell lymphoma (DLBCL), 10% (n=5) had follicular lymphoma and 10% (n=5) with primary mediastinal B-cell lymphoma (PMBCL). Before CAR-T infusion, 90% (n=45) had an advanced stage (III-IV). Secondary CNS disease involvement was found in 12% (n=6). Prior to CAR-T, 16% (n=8) had autologous stem cell transplant. The median follow-up was 7.6 months.
At day 30 post CART infusion, overall response rate for the total 50 pts based on PET/CT was as follows: Complete response (CR): 52%, Partial response (PR): 28%, Disease progression (DP): 16% and 4% (n=2) died before day 30 assessment. For 2nd line group: CR: 58%, PR: 21%, and DP: 21%. For 3rd line or beyond group: CR: 48%, PR: 32%, DP: 13%, and 6% (n=2) died before assessment.
At 12 months, Overall survival (OS) for all pts was 74.9 %, while it was 94.7% and 68.5% in 2nd line and 3rd line or beyond groups, respectively. Progression-free survival (PFS) was 55%, whereas it was 56.8% and 53.8% in 2nd line and 3rd line or beyond groups, respectively. In addition, OS and PFS were assessed based on day 30 response. The analysis of those who had CR by day 30 showed an OS of 91.1% and PFS of 75.8% at 12 months. On the other hand, an OS of 73.8% and PFS of 56.3% at 12 months was shown in patients who had PR at day 30. Pts with DP at day 30 had an OS of 62.5% at 6 months, which could be attributed to the use of CD3/20 bispecific antibody (Glofitamab) in five out of these seven patients. Out of the 50 pts, 4 pts had T-Cell histiocyte rich B-cell lymphoma, three of them (75%) had DP at day 30 and died, while one had PR in the last follow-up.
Regarding adverse effects, cytokine release syndrome (CRS) occurred in 46 pts (92%). CRS incidence in 2nd line group and 3rd line or beyond group was similar (88.8% and 91.6%, respectively). Out of the 92%, 88% had CRS grade I-II, while 4% had CRS grade III-IV. At 12 months, OS and PFS for pts who had CRS Grade I-II were 78.1% and 58.3%, respectively, compared to an OS of 50% and a PFS of 50% for grade III-IV. However, only 2 pts had grade III-IV. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 19 pts (38%). ICANS incidence in 2nd line group and 3rd line or beyond group was 33.3% and 45.8%, respectively. Out of the 38%, 22% had ICANS grade I-II while 16% had ICANS grade III-IV. The OS and PFS at 12 months for pts who had ICANS Grade I-II were 72.7% and 54.5%, respectively, while at 6 months for grade III-IV they were 75% and 70%, respectively.
There were 19 pts (38%) who had a relapse post CART, of whom, 14 pts received CD3/20 bispecific antibody (BsAb). The overall response rate (ORR) to BsAb was 43% (6 pts), one of them had CR (7%). At three months, the OS for those who received CD3/20 BsAb was 84.4% compared to 36.2% for those who did not receive it (p-value of 0.02). This significant difference can be explained by both the effect and possible synergic effect of BsAb therapy. Also, some of those who were not eligible for treatment with BsAb had an aggressive disease and were treated with palliative intent.
In conclusion, presented data shows comparable outcomes and toxicity rates to ZUMA-1 and ZUMA-7 in patients of Arab descent. Also, it suggests that BsAbs are effective salvage therapy for relapsed B-Cell lymphoma post CAR-T with reasonable response rate. However, further prospective studies are needed to demonstrate efficacy and safety.