CD 19 CAR T-Cell Therapy in R/R B Cell Malignancies : A Real World Experience from CAR T Working Group, Delhi Ncr ,India

Indigenously developed humanized CD-19 CAR T-cell therapy ( Actalycabtagene Autoleucel , NexCAR-19, ImmunoACT) has become available very recently in India.

We report here our early real world experience, of CAR T-cell therapy in RR DLBCL and RR B-ALL from 3 major cancer centres in northern India (Delhi-NCR CAR T working group).

15 patients were treated DLBCL -12 , B-ALL -3 from January 2023 to June 2024. The median age was 49 years (19-74) ,6 were males , 9 ,females.

There was one patient of Refractory DLBCL for whom Leukapheresis was done but he succumbed to severe pneumonia a few days after leukapheresis and could not be infused and has not been included in this analysis.

Median viability was 95.5 % at thawing .

13 patients (10 DLBCL , 3 B-ALL were treated with indigenously manufactured humanized NexCAR-19 and 2 patients (both DLBCL), were treated with AUXICART-19 (manufactured in Malaysia, humanized, compassionate access).

12 patients were ECOG PS1 , while 3 patients were PS-2 (2 DLBCL, 1 B-ALL) . Median number of prior treatment lines was 2 (1-6).

Out of 12 patients with DLBCL , 7 were Non-GCB type , 2 were GCB type and 3 were unspecified on IHC . Median Leukapheresis to infusion time was 31 days. Follow up time till date is 33-325 days (Median 146 days )

At the time of CAR T infusion 4 patients (all DLBCL) were in CR post debulking/bridging therapy and 11 had active disease (AD). Median CAR T dose was 9 million/kg (2-17), . The median baseline IgG level was 779 mg/dl (475-1247) and median trough level post CAR T-cell infusion was 566 mg/dl (319-972).

11/15 patients received debulking treatment ( Acalabrutinib -Lenalidomide in 3 , Polatuzumab based in 4, R-GEMOX in 2 , Venetoclax -Lenalidomide in 1 , orbital RT in 1 ALL with an orbital lymphomatous mass) while 8/15 received bridging therapy (VIPOR in 1, Gemcitabine -Cyclophosphamide in 1, GEMOX in 1 , Acalabrutinib Lenalidomide in 2, Pola-BR in 1, Procarbazine, Cyclophosphamide, Etoposide, Prednisone + Ara-c in 1 B-ALL) .

CRS was seen in 10 patients (3 of 5 in CR group and 7 of 10 in AD group), ICANS was seen in 3 patients (grade 3 in 2 patients , 1 in CR group and 1 in AD). 2/3 patients who had ICANS had history of CNS disease . In 1 patient with DLBCL , with excessive somnolence and unresponsiveness ( negative for CNS infection and CNS lymphoma ) was recognised as delayed ICANS after day +90. She rapidly responded to pulse methylprednisone and is now on salvage Pola-Glofitamab doing well. CRS was grade 3 in 1 patient and grade 1-2 in the rest.

Day 30 responses for DLBCL were 5 CR, 3 PR and 3 PD and 1 stable disease. All 4 baseline CR remained in CR at day 30 and 1 in the AD group achieved CR.

All patients in PR/SD at day 30 have progressed. While 1 patient in baseline CR progressed at Day 90 (she had secondary CNS lymphoma).

Out of those DLBCL who have completed 3 months follow up, 4 are in CR and 2 patients of these have completed 6 months in CR .

3 patients of Refractory B-ALL , 1 Ph like and 1 P53 mutated , ( 19 Y/M ,0.01 % MRD , and 62/F with 90 % blasts in marrow) and another with treated CNS disease and ocular lymphomatous mass received CAR T. 2 patients achieved MRD negative remission tested with Next generation flow cytometry on Day 30 while NGS based MRD result (BCR clonality) is awaited . One patient with florid ALL had persistent grade 2-3 CRS and required 4 doses of Tocilizumab. Both patients had received prior Inotuzumab and were refractory to multiple lines and one patient had advanced liver fibrosis as a comorbidity. The second patient had Inotuzumab and ATT induced liver damage. The third patient who had history of CNS disease and an ocular mass (post RT) and had 30 % marrow blasts succumbed to severe infection post CAR- T in pancytopenia.

9/15 patients required Tocilizumab for CRS, 1 patient required Anakinra (HLH ) and 7/15 required steroids for CRS/ICANS. 11/15 patients required IVIG replacement post therapy . All 4 patients of DLBCL who lost B cell aplasia had PD eventually and 4/8 patients maintaining B cell aplasia relapsed post CAR T. 1 patient of DLBCL with PD post CAR T achieved CR with Glofitamab +Polatuzumab combination and is alive in CR

Only 1 patient ( with florid refractory B-ALL) required pressor support and ICU transfer.

Overall , our initial experience with indigenously manufactured humanized CD-19 CAR T-cells is encouraging . Safety is good and initial efficacy seems promising .

No relevant conflicts of interest to declare.