In the Journals

CD19-specific CAR T-cell therapy feasible for aggressive non-Hodgkin lymphoma

CD19-specific chimeric antigen receptor T-cell therapy after high-dose chemotherapy and autologous stem cell transplant appeared feasible for patients with relapsed or refractory B-cell non-Hodgkin lymphoma, according to a prospective phase 1 study published in Blood.

However, further study is needed to determine the treatment’s efficacy because the cohort analyzed was too small to make a definitive determination, researchers wrote.

“High-dose chemotherapy followed by autologous stem cell transplantation is the established standard of care for patients with relapsed or primary refractory diffuse large B-cell lymphoma,” Craig S. Sauter, MD, clinical director of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, and colleagues wrote. “Unfortunately, long-term OS and PFS is [about] 50% following [this approach], despite investigational conditioning or maintenance interventions.”

The FDA has approved two chimeric antigen receptor (CAR) T-cell therapies. One is approved for relapsed or refractory large B-cell lymphoma, including DLBCL. The other is approved for treatment of DLBLC, as well as children or young adults with acute lymphoblastic leukemia.

In their study, Sauter and colleagues enrolled 15 patients (median age, 61 years; range, 34-75) with relapsed or refractory B-cell non-Hodgkin lymphoma. Seven of the patients had received three or more prior lines of therapy.

Patients underwent high-dose chemotherapy followed by autologous stem cell transplantation. They then underwent infusion with second-generation 19-28z CAR T cells on day 2 (two-thirds of dose) and day 3 (one-third of dose) after transplant.

Fourteen patients received 5 x 106 CAR T cells/kg. One patient received 1 x 107 CAR T cells/kg but, because that patient experienced severe cytokine release syndrome, investigators decided not to use that dose level for any other patients.

After media follow-up of 24 months (range, 12-37), four patients remained alive without disease progression.

Researchers reported PFS rates of 40% (95% CI, 20-70) at 1 year and 30% (95% CI, 20-70) at 2 years.

Sauter and colleagues observed no difference in persistence of CAR T-cell therapy between patients who experienced progression or death (median, 8 days; range, 1-22) and those who remained alive with no progression (median, 8 days; range, 6-22).

Ten patients (67%) experienced grade 3 or grade 4 neurotoxicity and/or seizures. Median time to the start of neurotoxicity was 5 days (range, 1-6) after CAR T-cell infusion, with resolution occurring after a median 9.5 days (range, 2-20).

Six of the 10 patients who experienced neurotoxicity six also developed grade 2 to grade 4 cytokine release syndrome at a median 2.5 days (range, 0-10) after infusion. Resolution occurred at a median 8 days (range, 3-12).

All cases of neurotoxicity and cytokine release syndrome resolved.

Patients who developed neurotoxicity demonstrated longer persistence of 19-28z CAR T cells (median, 11 days; range, 4-22) than those who did not develop neurotoxicity (median, 4 days; range, 1-8; P = .05).

“We have demonstrated the feasibility of 19-29z CAR T administration following [high-dose chemotherapy and autologous stem cell transplantation] for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma,” Sauter and colleagues wrote. “The therapy was met with a large burden of reversible neurotoxicity, potentially related to the high-dose conditioning prior to [CAR T cell infusion]. ... [Although] long-term durability of this therapy was seen in only a few subjects, the high-risk characteristics of this relatively small phase 1 study population limits efficacy determination.” – by John DeRosier

 

Disclosures: Sauter reports consultant fees and research funding from Juno Therapeutics. Please see the study for all other authors’ relevant financial disclosures.

CD19-specific chimeric antigen receptor T-cell therapy after high-dose chemotherapy and autologous stem cell transplant appeared feasible for patients with relapsed or refractory B-cell non-Hodgkin lymphoma, according to a prospective phase 1 study published in Blood.

However, further study is needed to determine the treatment’s efficacy because the cohort analyzed was too small to make a definitive determination, researchers wrote.

“High-dose chemotherapy followed by autologous stem cell transplantation is the established standard of care for patients with relapsed or primary refractory diffuse large B-cell lymphoma,” Craig S. Sauter, MD, clinical director of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, and colleagues wrote. “Unfortunately, long-term OS and PFS is [about] 50% following [this approach], despite investigational conditioning or maintenance interventions.”

The FDA has approved two chimeric antigen receptor (CAR) T-cell therapies. One is approved for relapsed or refractory large B-cell lymphoma, including DLBCL. The other is approved for treatment of DLBLC, as well as children or young adults with acute lymphoblastic leukemia.

In their study, Sauter and colleagues enrolled 15 patients (median age, 61 years; range, 34-75) with relapsed or refractory B-cell non-Hodgkin lymphoma. Seven of the patients had received three or more prior lines of therapy.

Patients underwent high-dose chemotherapy followed by autologous stem cell transplantation. They then underwent infusion with second-generation 19-28z CAR T cells on day 2 (two-thirds of dose) and day 3 (one-third of dose) after transplant.

Fourteen patients received 5 x 106 CAR T cells/kg. One patient received 1 x 107 CAR T cells/kg but, because that patient experienced severe cytokine release syndrome, investigators decided not to use that dose level for any other patients.

After media follow-up of 24 months (range, 12-37), four patients remained alive without disease progression.

Researchers reported PFS rates of 40% (95% CI, 20-70) at 1 year and 30% (95% CI, 20-70) at 2 years.

Sauter and colleagues observed no difference in persistence of CAR T-cell therapy between patients who experienced progression or death (median, 8 days; range, 1-22) and those who remained alive with no progression (median, 8 days; range, 6-22).

Ten patients (67%) experienced grade 3 or grade 4 neurotoxicity and/or seizures. Median time to the start of neurotoxicity was 5 days (range, 1-6) after CAR T-cell infusion, with resolution occurring after a median 9.5 days (range, 2-20).

Six of the 10 patients who experienced neurotoxicity six also developed grade 2 to grade 4 cytokine release syndrome at a median 2.5 days (range, 0-10) after infusion. Resolution occurred at a median 8 days (range, 3-12).

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All cases of neurotoxicity and cytokine release syndrome resolved.

Patients who developed neurotoxicity demonstrated longer persistence of 19-28z CAR T cells (median, 11 days; range, 4-22) than those who did not develop neurotoxicity (median, 4 days; range, 1-8; P = .05).

“We have demonstrated the feasibility of 19-29z CAR T administration following [high-dose chemotherapy and autologous stem cell transplantation] for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma,” Sauter and colleagues wrote. “The therapy was met with a large burden of reversible neurotoxicity, potentially related to the high-dose conditioning prior to [CAR T cell infusion]. ... [Although] long-term durability of this therapy was seen in only a few subjects, the high-risk characteristics of this relatively small phase 1 study population limits efficacy determination.” – by John DeRosier

 

Disclosures: Sauter reports consultant fees and research funding from Juno Therapeutics. Please see the study for all other authors’ relevant financial disclosures.

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