CAR T-Cell Therapies Old and New: Cilta-Cel Wows in Multiple Myeloma; Axi-Cel Shows 44% OS at 4 Years in LBCL


Results were released for a leading chimeric antigen receptor (CAR) T-cell therapy candidate in multiple myeloma, along with long-term findings for an early treatment that may soon face competition.

Chimeric antigen receptor (CAR) T-cell therapy is no longer the new kid on the block at the 62nd American Society of Hematology (ASH) annual meeting, but results for this groundbreaking treatment still excite as the technology moves beyond acute lymphoblastic leukemia and different forms of lymphoma to multiple myeloma.

Saturday’s virtual presentation featured phase 1b/2 results for ciltacabtagene autoleucel (cilta-cel), Janssen’s investigational B-cell maturation antigen (BCMA) CAR T-cell treatment for patients whose multiple myeloma has progressed after as many as 6 treatments.

Cilta-cel produced an overall response rate (ORR) of 97% and a stringent response rate of 67% with a median follow-up time of 12.4 months, according to data presented by Deepu Madduri, MD, of The Tisch Cancer Institute at Mount Sinai, New York, and the principal investigator of CARTITUDE-1.1

Median duration of response and progression-free survival (PFS) were not reached.

Patients with multiple myeloma have a poor prognosis if their disease progresses after 3 treatments, Madduri said, with a typical overall survival (OS) of less than 6 months. But in CARTITUDE-1, cilta-cel has produced deep responses in these patients. “I think a one-time treatment to give these deep, durable responses is what we need for our myeloma patients. It’s one step closer to getting a cure.”

Madduri told The American Journal of Managed Care® in an interview there was no correlation between the number of prior treatments and the patients’ response. “We had a median of 6 prior lines of therapy—it ranged anywhere from 3 to 18 prior lines of therapy.”

Results from the open-label study presented at ASH covered 97 patients, who were 58.8% male with median age of 61 years. Data showed the following:

  • 12-month PFS was 77% (95% CI, 66%-84%), and the 12-month OS rate was 89% (95% CI, 80%-94%).
  • Patients typically responded within the first month, and manufacturing of the treatment was successful for all patients.
  • 93% of the patients achieved minimal residual disease, an important marker.
  • In the combined results, the most common hematologic adverse events (AEs) were neutropenia (96%), anemia (81%), thrombocytopenia (79%), leukopenia (62%), and lymphopenia (53%).

Cytokine release syndrome (CRS), a common AE of CAR T-cell treatment, was seen in 95% of the patients, lasting for 4 days (range, 1-97), with 99% of the cases resolving within 14 days. Of those with CRS, 95% (n = 87) were grade 1 or 2, 3% (n = 3) were grade 3, and 1 was grade 4. The statement from Janssen reported 1 "Grade 5" AE, or death from CRS; Madduri told the session that overall, 6 people have died due to AEs from treatment.

The median onset of CRS was 7 days after infusion, with 89% not seeing CRS until day 4, which could show the potential for cilta-cel to be given in an outpatient setting.

Asked during the session to offer a possible reason why CRS starts later with cilta-cel, Madduri said, "We think this is probably related to cell expansion, because it expands a little bit later than some of the other therapies."

Neurotoxicity was seen in 21% of the patients, with 10% (n = 10) have neurotoxicity of grade 3 or higher, including 1 death. Immune effector cell–associated neurotoxicity syndrome was seen in 16 patients and typically occurred alongside CRS. Other cognitive effects were seen in 12 patients that generally occurred after CRS had resolved.

Madduri said clinicians have become more adept at managing toxicities. “We tend to give tocilizumab much earlier now, not necessarily waiting until grade 2 CRS—so I feel these patients are managed easily with the supportive care that we have.”

Long-term results for axi-cel. The long-term promise of CAR T-cell therapy was seen in 4-year results for axicabtagene ciloleucel (axi-cel) in adult patients with refractory large B-cell lymphoma (LBCL). Sold as Yescarta (Kite Pharma/Gilead), this was the first CAR T-cell therapy approved for this indication and the second overall.2

Kite Pharma announced long-term follow-up data for the ZUMA-1 trial; among 101 patients at least 4 years past a single infusion of axi-cel (median follow-up, 51.1 months), a Kaplan-Meier estimate of OS was 44%. The 101 patients who had refractory LBCL were among 111 patients enrolled in the original phase 2 ZUMA-1 trial. These patients had a median period of less than 2 months from leukapheresis to complete response. Also, no treatment-related secondary malignancies have been reported.

“With close to half of patients still alive after a single infusion of axicabtagene ciloleucel, we are transforming the way relapsed or refractory large B-cell lymphoma can be treated,” Frederick L. Locke, MD, said in a statement. Locke was the co-lead investigator of ZUMA-1 and is the vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida. “I continue to see these patients in the clinic, and this overall survival data confirms the durability of CAR T-cell therapy in a patient population that previously exhausted all viable treatment options.”

Of note, the investigators reported results from 21 patients with blood samples at the 3-year mark, and for 14 patients (67%), the CAR-marked cells were still detectable. Normal B cells were also found in 91% of evaluable patients, which investigators said suggest that the effects of treatment last beyond the persistence of functional CAR T cells.

Axi-cel’s long-term results come as Kite Pharma/Gilead face possible competition from lisocabtagene maraleucel (liso-cel), an investigational therapy from Bristol Myers Squibb. Liso-cel would treat the patients with diffuse LBCL, but it involves a different manufacturing process that could lessen the effects of CRS when the patients receive the therapy. The FDA missed a target date for action due to delays inspecting a manufacturing facility, but approval is still possible before the end of 2020.

Results from the OUTREACH study presented Saturday also suggest liso-cel can safely be administered in an outpatient setting,3 and an abstract for results scheduled to be presented Sunday suggests substantial savings when liso-cel is administered in the outpatient setting compared with the inpatient setting.4


1. Madduri D, Berdeja JG, Usmani SZ, et al. CARTITUDE-1: phase 1b/2 Study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, in relapsed/refractory multiple myeloma. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Abstract 177.

2. Jacobson C, Locke FL, Ghobadi A, et al. Long-term survival and gradual recovery of B cells in patients with refractory large B cell lymphoma treated with axicabtagene ciloleucel (axi-cel). Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Abstract 1187.

3. Godwin JE, Freytes CO, Maris M, et al. Outcomes of treatment with the chimeric antigen receptor (CAR) T cell therapy lisocabtagene maraleucel (liso-cel) in the nonuniversity setting: initial results from the Outreach study. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Abstract 1196.

4. Palomba ML, Jun MP, Garcia J, et al. Costs of postinfusion monitoring by site of care for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) who received third-line or later treatment with lisocabtagene maraleucel (liso-cel) in the Transcend NHL 001 and Outreach trials. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Abstract 2514.

Maggie L. Shaw contributed to this report.

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