Two lymphoma trials show promise with CAR T cell therapy

Dr. Joseph Delano Fule Robles
20 Jul 2017
Two lymphoma trials show promise with CAR T cell therapy

Two trials on chimeric antigen receptor (CAR) T cell therapy showed positive responses in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL) or transformed follicular lymphoma (TFL), according to findings presented at the recent European Hematology Congress 2017 held in Madrid, Spain.

In the single-arm, open-label, multicentre, global phase II JULIET trial of 141 patients with relapsed or refractory DLBCL treated with a 3.1 x 108 median dose of CTL019, the best overall response rate (ORR) was 59 percent (p<0.001), with a complete remission (CR) rate of 43 percent and a partial remission rate of 16 percent. [EHA 2017, abstract LB2604; Hematol Oncol 2017, doi:10.1002/hon.2437_6]

Cytokine release syndrome (CRS) occurred in 57 percent of patients, with 24 percent being admitted to the intensive care unit and 8 percent being intubated. Tocilizumab was given to 16 percent of patients with CRS and there were no CRS-associated deaths.

Grade 3–4 cytopenias and febrile neutropenias lasting for ≥28 days occurred in 21 and 14 percent of patients, respectively. Neurologic adverse effects (AEs), which were managed with supportive care, occurred in 13 percent of patients.

“The median age of DLBCL patients is almost 62 years. Hence, being able to develop a therapy for those who may not be good candidates for autologous stem cell transplantation [ASCT] represents [significant] progress… Adverse events were reversible and effectively managed by trained personnel in our study,” commented investigator Dr Gilles Salles of the Hospices Civils de Lyon, Lyon, France.

In the multicentre ZUMA-1 trial of 101 patients with refractory or relapsed DLBCL, PMBCL or TFL treated with axicabtagene ciloleucel at a target dose of 2 x 106, the ORR reached 82 percent (p<0.0001), with 39 percent of patients experiencing CR. The median duration of response was 8.2 months. [EHA 2017, abstract S446]

CRS occurred in 13 percent of patients and neurologic AEs occurred in 28 percent of patients. Other grade 3 or higher AEs included neutropenia (66 percent), leukopenia (44 percent), anaemia (43 percent), febrile neutropenia (31 percent) and encephalopathy (21 percent).

“The CR rate was seven-fold higher compared with historical controls, and nearly half of the patients had ongoing response… The use of tocilizumab and steroids for managing AEs did not decrease clinical response [to axicabtagene ciloleucel]” commented investigator Dr Yi Lin of Mayo Clinic, Rochester, Minnesota, US.

In a study presented at the recent American Association for Cancer Research (AACR) 2017 Annual Meeting, immunologic biomarkers such as interleukin (IL)-15, IL-10 and granzyme B were found to increase within 7 days of treatment with axicabtagene ciloleucel in the ZUMA-1 trial, with a ≥2-fold induction above baseline for CRS and neurologic AEs. [AACR 2017, abstract CT020] 

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