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Published on: February 17, 2022
KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma
Michael Wang1, Javier Munoz1, Andre Goy1
1From the University of Texas M.D. Anderson Cancer Center, Houston (M.W.), and Texas Oncology, Dallas (H.H.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (J.M.); John Theurer Cancer Center, Hackensack, NJ (A.G.); Moffitt Cancer Center, Tampa (F.L.L.), and the University of Miami, Miami (A.B.) - both in Florida; Dana-Farber Cancer Institute, Boston (C.A.J.); Cleveland Clinic Foundation, Cleveland (B.T.H.), and the Ohio State University Comprehensive Cancer Center, Columbus (S.J.); David Geffen School of Medicine at UCLA, Los Angeles (J.M.T.), Stanford University School of Medicine, Stanford (D.B.M.), and Kite, a Gilead company, Santa Monica (W.P., L.Z., J.M.R., R.K.J., A.V.R.) - all in California; Sarah Cannon Research Institute-Tennessee Oncology, Nashville (I.W.F.); Colorado Blood Cancer Institute, Denver (P.A.M.); Swedish Cancer Institute, Seattle (J.M.P.); the Academic Medical Center, University of Amsterdam, Amsterdam, for the Lunenburg Lymphoma Phase I/II Consortium (M.-J.K.); Centre Hospitalier Universitaire (CHU) Bordeaux, Service d'Hematologie et Therapie Cellulaire, Bordeaux (N.M.), and CHU Rennes, INSERM French Blood Establishment, Rennes (R.H.) - both in France; Fox Chase Cancer Center, Philadelphia (H.F.); Universitätsklinikum Würzburg, Würzburg, Germany (M.S.T.); and the University of Rochester Medical Center, Rochester, NY (P.M.R.).
Background:
Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton's tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma.
Methods:
In a multicenter, phase 2 trial, we evaluated KTE-X19 in patients with relapsed or refractory mantle-cell lymphoma. Patients had disease that had relapsed or was refractory after the receipt of up to five previous therapies; all patients had to have received BTK inhibitor therapy previously. Patients underwent leukapheresis and optional bridging therapy, followed by conditioning chemotherapy and a single infusion of KTE-X19 at a dose of 2×106 CAR T cells per kilogram of body weight. The primary end point was the percentage of patients with an objective response (complete or partial response) as assessed by an independent radiologic review committee according to the Lugano classification. Per the protocol, the primary efficacy analysis was to be conducted after 60 patients had been treated and followed for 7 months.
Results:
A total of 74 patients were enrolled. KTE-X19 was manufactured for 71 patients and administered to 68. The primary efficacy analysis showed that 93% (95% confidence interval [CI], 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred.
Conclusions:
KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma. The therapy led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies. (Funded by Kite, a Gilead company; ZUMA-2 ClinicalTrials.gov number, NCT02601313.).
Insights
Chimeric antigen receptor (CAR) T-cell therapy KTE-X19 shows high response rates in patients with relapsed or refractory mantle-cell lymphoma. This therapy offers durable remissions but carries risks of serious adverse events.
Area of Science:
- Hematology
- Oncology
- Immunotherapy
Background:
- Mantle-cell lymphoma (MCL) that relapses or progresses after Bruton's tyrosine kinase (BTK) inhibitor therapy has a poor prognosis.
- Chimeric antigen receptor (CAR) T-cell therapy, specifically KTE-X19 targeting CD19, is being investigated for its potential benefit in this patient population.
Purpose of the Study:
- To evaluate the efficacy and safety of KTE-X19 in patients with relapsed or refractory MCL who have previously received BTK inhibitor therapy.
Main Methods:
- A multicenter, phase 2 trial involving patients with relapsed/refractory MCL after up to five prior therapies, including BTK inhibitors.
- Patients received conditioning chemotherapy followed by a single infusion of KTE-X19 (2x10^6 CAR T cells/kg).
- Primary endpoint was objective response rate assessed by independent radiologic review.
Main Results:
- An objective response rate of 93% (67% complete response) was observed in the primary efficacy analysis of 60 patients.
- In an intention-to-treat analysis of 74 patients, 85% achieved an objective response (59% complete response).
- At 12 months, progression-free survival was 61% and overall survival was 83%; common grade 3+ adverse events included cytopenias (94%) and infections (32%).
Conclusions:
- KTE-X19 demonstrated durable remissions in a majority of patients with relapsed or refractory MCL.
- The therapy is associated with serious and potentially life-threatening toxicities consistent with other CAR T-cell therapies.
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