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CAR T cells
Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.
One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).
Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).
A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.
ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.
Ibrutinib
In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.
Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.
Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.
Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.
These findings are “early and preliminary but very exciting” Dr. Brodsky said.
Checkpoint inhibitors
Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.
The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.
CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.
Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.
Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.
There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.
“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.
“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”
Tisagenlecleucel follow-up
One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.
The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.
The probability of relapse-free survival was 66% at 12 months and 18 months.
“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.
The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).
The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.
HSCT consolidation
Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).
Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.
Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.
There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.
Of the 23 patients who did not undergo another HSCT, eight are still in remission.
“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.