CAR T-cell therapeutics

Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19...Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time.

Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19...Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time.

Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19...Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time.

Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19...Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time.

Patients received lymphodepletion with fludarabine and cyclophosphamide (n=21) followed by axicabtagene ciloleucel (n=15, 71%) and tisagenlecleucel (n=6, 29%) between 3/14/18 and 7/12/19...Outbreaks of vaccine preventable illnesses have occurred over the past several years in areas with lower rates of immunization, and it is therefore important to ensure immunity, if possible, in immunocompromised patients. Longer follow-up will also be needed to see if responses wane over time.

The median number of prior anticancer treatment regimens was 7; all patients had received prior daratumumab therapy; 4 (22%) patients had received prior BCMA-targeted antibody–drug conjugate or chimeric antigen receptor T-cell therapy. Clinicaltrials.gov identifier: NCT03269136. Funding: Pfizer.

Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 d were used for lymphodepletion. Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated pts with MM with a safety profile consistent with LEGEND-2. Further investigation of cilta-cel in other MM populations is underway.

Background: CD19-targeted chimeric antigen receptor T-cell therapies (CART) have remarkable overall response rates (ORR) for relapsed/refractory diffuse large B cell lymphoma (DLBCL)...Pts received axicabtagene ciloleucel (axi-cel, 68%) or tisagenlecleucel (tisa-cel, 32%) following lymphodepletion (LD) with median Aph to infusion time of 35d (range 20–77)...Tocilizumab and steroid use rates were 45% and 41%, respectively and did not differ by BI (p=0.2, p=0.8)...Early data suggest that RT or CMT may be a preferable BI strategy compared to ST though larger cohorts are needed for validation and to clarify the unique impact of RT without ST. More intensive cytoreductive strategies might be beneficial for bulky disease pre-CART.

Patients received axicabtagene ciloleucel (Yescarta®) (34/46, 74 %) or tisagenlecleucel (Kymriah ®) (12/46, 26 %)...Lymphodepletion regimens were either cyclophosphamide/fludarabine (n=43, 93%) or bendamustine (n=3, 7%)...Nephrotoxic medication exposures prior to AKI included acyclovir in 10 (71%), vancomycin in 11 (79%) and ibuprofen in 1 (7%)... Our study shows that the incidence of AKI is low in patients receiving CAR T therapy. Majority of AKI was grade 1 and returned to baseline within 30 days. A larger study sample will likely help elucidate risk factors associated with development of AKI in these patients.

Median number of prior therapies was 1, including 8 pts w/ previous allogeneic hematopoietic cell transplant (alloHCT) and 5 w/ prior chimeric antigen receptor T-cell therapy (CAR-T)...One pt w/ grade 2 CRS received tocilizumab for hypotension suboptimally responsive to fluid boluses (FB) w/ IL-6 level = 25754 pg/mL...Peak APR levels correlated w/ CRS severity. Authors noted concordance of CRS grading between CTCAE and ASTCT, suggesting the feasibility of a single, BITE-specific grading system.