For the primary time, a chimeric antigen receptor (CAR) remedy has yielded a excessive response charge amongst sufferers with relapsed/refractory indolent non-Hodgkin lymphoma (iNHL), together with sufferers with follicular lymphoma (FL) and marginal zone lymphoma (MZL).
The brand new outcomes come from the ZUMA-5 trial with axicabtagene ciloleucel (axi-cel; Yescarta), wherein responses have been seen in additional than 90% of trial members.
The outcomes might result in new indication for the product, which has already been approved for the remedy of huge B-cell lymphoma for sufferers who expertise illness development with not less than two prior strains of remedy. The approval was based mostly on knowledge from the ZUMA-1 trial.
The brand new knowledge have been reported on the American Society of Hematology (ASH) 2020 Annual Assembly by Caron Jacobson, MD, the Dana-Farber Most cancers Institute, Boston, Massachusetts.
She mentioned the info confirmed response charges of greater than 90% amongst sufferers with iNFL, together with sufferers with FL and MZL.
Information from ZUMA-5 in iNHL have been extra favorable than these seen in ZUMA-1 for sufferers with aggressive lymphomas.
“We have been very impressed with the magnitude of the responses, and in addition the sturdiness,” Jacobsen mentioned in an institute assertion. “This remedy has meaningfully impacted high-risk sufferers with these ailments. I used to be additionally struck early on by how favorable the security profile was in comparison with what we have been seeing within the fast-growing lymphomas.”
Approached for remark, Gary Schiller, MD, professor of drugs and director of the Hematological Malignancy/Stem Cell Transplant Program on the David Geffen Faculty of Drugs, College of California, Los Angeles, agreed.
“I discovered the outcomes stunning, as a result of the hostile occasion profile is extra favorable than that seen for the opposite aggressive lymphomas. Even response charges are higher than those seen in aggressive illness, resembling ALL [acute lymphoblastic leukemia] and DLBCL [diffuse large B-cell lymphoma],” Schiller informed Medscape Medical Information.
In scientific observe, Schiller has used CAR T-cells for sufferers with diffuse giant B-cell lymphoma, a sign specified on the present product labeling. He famous that prior authorization is required for sufferers with industrial insurance coverage, however he mentioned his sufferers have by no means been denied entry. For these sufferers, he sometimes makes use of axi-cel after the second relapse.
Schiller identified that CAR T-cell remedy is evolving and that the toxicity profile of the remedy wants enchancment, however he famous that “on this research, there was a low charge of grade 3/4 cytokine launch syndrome — a extra daunting aspect impact of CAR T-cell remedy.”
“If permitted for this indication [iNHL], I might think about using it,” Schiller mentioned.
Though different choices can be found for sufferers with iNHL, resembling Bruton tyrosine kinase inhibitors, typical chemoimmunotherapy, and PI3K [phosphatidyl inositol-3 kinase] inhibitors, Schiller famous that two thirds of sufferers have already acquired greater than three prior strains of remedy and no different remedy choices could also be out there.
“The research has convincingly demonstrated the unprecedent responses of CAR T-cells on closely pretreated sufferers with FL, particularly for individuals who have failed a number of regimens,” Henry Fung, MD, chair of the Division of Bone Marrow Transplant and Mobile Therapies, Fox Chase Most cancers Middle, Philadelphia, Pennsylvania, informed Medscape Medical Information. He predicted that axi-cell “will grow to be a vital choice for these sufferers.”
Fung famous that regardless of the efficacy of CAR T-cell remedy, only a few sufferers with superior refractory illness are prone to expertise a long-lasting response. “Now, we’d like research to outline the very best time for this groundbreaking remedy and who will profit probably the most. The final word aim needs to be reaching a sturdy remission and presumably treatment,” Fung informed Medscape Medical Information.
Ongoing scientific trials are exploring earlier use of CAR T-cells, Jacobsen commented. For instance, CAR T-cell remedy is being examined within the second-line setting towards salvage chemotherapy or autologous stem cell transplants for sufferers with high-risk illness.
Some outcomes have been reported. For instance, outcomes of ZUMA-12 that have been introduced on the ASH assembly present that for sufferers with high-risk giant B-cell lymphomas who didn’t expertise a whole response to 2 cycles of an anti-CD20 monoclonal antibody and an anthracycline-containing routine did expertise a response to CAR T-cell remedy. This research will present insights into the efficacy of CAR T-cells within the pseudo first-line setting, Jacobsen commented.
ZUMA-5 Examine Particulars
ZUMA-5 was a multicenter, single-arm, part 2 research that concerned sufferers with relapsed or refractory iNHL who had acquired not less than two prior strains of remedy.
Information have been reported for 124 sufferers with FL and 22 sufferers with MZL. All sufferers had acquired CAR T-cells that had been made individually for every affected person. About half the sufferers had cumbersome illness; 64% had acquired not less than three prior strains of remedy; and 23% had acquired prior autologous stem cell transplants.
The median follow-up for efficacy was 17.5 months. The efficacy knowledge for 104 sufferers (FL: 84 sufferers; MZL: 20 sufferers) confirmed an total response charge of 92% (FL: 94%; MZL: 85%) and a whole response (CR) charge of 76% (FL: 80%; MZL: 60%). Excessive response charges have been seen throughout all teams of sufferers no matter tumor burden, quantity, and kind of prior therapies.
The 12-month period of response was 71.7% for all sufferers and 77% for sufferers with FL. It was not evaluable for these with MZL.
One-year progression-free survival was 73.7%, and 1-year total survival was 92.9%.
Security knowledge have been reported for all 146 sufferers who acquired CAR T-cells. Many of the grade ≥3 unintended effects have been cytopenias (70%) and infections (16%). Three sufferers died; one demise, from CRS, was attributed to axi-cel.
CRS was seen in 82% of sufferers (grade ≥3 CRS: 7%). The median time to onset was 4 days, and the median period was 6 days. At knowledge cutoff, no affected person had ongoing CRS.
Grade ≥3 neurologic occasions have been reported in 15% of sufferers with FL and in 41% of sufferers with MZL.
Response charges have been barely greater and charges of hostile occasions have been barely decrease amongst sufferers with FL than amongst these with MZL, Jacobson famous.
The ZUMA-5 trial was sponsored by Kite/Gilead, producer of axi-cel. Jacobson has disclosed no related monetary relationships. Schiller reported honoraria/analysis funding/consultancy/inventory possession from AbbVie, Actinium, Actuate, Agios Prescription drugs, Amgen, AROG, Astellas, Bristol-Myers Squibb, Celgene, Constellation Prescription drugs, Daiichi Sankyo, Deciphera, Delta-Fly, Forma, FujiFilm, Gamida, Genentech, Geron, Gilead, Glycomimetics, Incyte, Jazz Prescription drugs, J&J, Juno, Karyopharm, Kite/Gilead, Mateon Therapeutics, MedImmune, Onconova, Pfizer, RegImmune, Samus, Sangamo Therapeutics, Sanofi, Stemline, Takeda, Tolero, and Trovagene. Fung reported being on the audio system’ bureaus of Jansen Oncology and Celgene/BMS.
American Society of Hematology (ASH) 2020 Annual Assembly: Abstract 700. Offered December 7, 2020.