Patients with relapsed diffuse large B cell lymphoma (DLBCL) who achieve a complete remission from interim chemotherapy while awaiting secondary chimeric antigen receptor (CAR) T cell therapy show significantly better outcomes if they then receive conventional autologous stem cell transplantation (auto-HCT), compared with CAR T therapy.
"In patients with relapsed DLBCL in a complete remission, treatment with auto-HCT is associated with a lower rate of relapse/progression, and a longer progression-free survival [versus CAR T therapy]," said first author Mazyar Shadman, MD, MPH, of the Division of Medical Oncology, University of Washington, Seattle.
"The data support utilization of auto-HCT in patients with relapsed LBCL achieving a complete response," he said.
The findings were presented at the annual meeting of the American Society of Hematology in San Diego.
While approximately 60% of patients with DLBCL are successfully treated after an initial anthracycline-based and rituximab-containing chemotherapy regimen, those who do not improve have poorer outcomes, and CAR T-cell therapy has emerged as the standard of care for those patients, based on results from the ZUMA-7 and TRANSFORM clinical trials.
But with delays in accessing CAR T quite common, patients will often receive interim chemotherapy while awaiting referral to a CAR T center, and occasionally, usually unexpectedly, some will achieve a partial or complete response.
In previous research involving patients who achieved a partial remission in such interim cases, Dr. Shadman and colleagues demonstrated that auto-HCT had favorable outcomes, compared with those who received CAR T therapy.
For the new retrospective, real-world analysis, the authors compared outcomes with the treatment options among 360 patients between the ages of 18 and 75 who were enrolled in the Center for International Blood & Marrow Transplant Research registry and had received auto-HCT or CAR T therapy after achieving a complete remission following salvage chemotherapy.
Of those receiving CAR-T cell therapy, most (53.2%) received tisagenlecleucel (tisa-cel), followed by axicabtagene ciloleucel (axi-cel, 45.6%) and lisocabtagene maraleucel (liso-cel, 1.3%), between 2018 and 2021, while 281 patients were treated with auto-HCT between 2015 and 2021.
With a median follow-up of 49.7 months (range 3.0-94.4) for auto-HCT and 24.7 months (range 3.3-49.4) for CAR-T, a univariate analysis showed the rate of 2-year progression free survival was 66.2% in the auto-HCT group and 47.8% in the CAR T group (P < .001).
The results also favored auto-HCT for 2-year progression/relapse, with a cumulative incidence of 27.8% with auto-HCT versus 48% with CAR T (P < .001), and the 2-year overall survival was higher with auto-HCT (78.9% vs. 65.6%; P = .037).
After adjustment in multivariable analysis adjusting for relevant clinical variables, auto-HCT versus CAR T remained associated with a lower risk of relapse or progression (HR 2.18; P < .0001) and an improved progression-free survival (HR 1.83; P = .0011), with no significant differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).
Deaths occurred among 85 patients in the auto-HCT group and 25 in the CAR T cohort, with lymphoma being the main cause of death in both groups (60% and 68%, respectively).
While 37 (13.2%) of auto-HCT patients later received subsequent CAR-T therapy, no patients receiving CAR-T had subsequent auto-HCT.
There were no differences between the CAR-T and auto-HST groups in rates of 2-year treatment-related mortality (4.1% vs. 5.9%; P = .673).
A subanalysis of those who had treatment failure at 12 months, (CAR-T = 57 and auto-HCT = 163) showed that those receiving CAR-T therapy had a higher 2-year relapse rate (46.3% vs. 25%; P < .001); an inferior 2-year progression-free survival rate (48.4% vs. 68.2%; P = .001) compared with auto-HCT, while there were no significant differences between the groups in terms of 2-year overall survival or treatment-related mortality.
After a multivariable analysis adjusting for relevant clinical factors, CAR-T therapy remained associated with higher risk of relapse (HR 2.18; P < .0001) and an inferior progression-free survival (HR 1.83; P = .0011) compared with auto-HCT, with no differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).
"These results are consistent with our previously reported findings, indicating higher efficacy of auto-HCT compared with CAR T in patients with partial remission," Dr. Shadman said.
In addition to the study's being a retrospective analysis, limitations include that more than half of patients in the CAR T cohort received tisa-cel, which could have lower efficacy compared with other approved CAR T therapies, Dr. Shadman noted.
"A repeat analysis by including more patients treated with axi-cel or liso-cel may address this issue in the future," he said.
Discussing the results in a press briefing, Dr. Shadman underscored that "there is no question the choice of therapy for these DLBCL patients with primary refractory disease should be second-line CAR T therapy — we are not suggesting that those patients should be sent for auto-HCT," he said.
"What we are saying is, in real-world practice... patients may need chemotherapy treatment in the interim (awaiting CAR T treatment), and we don't expect these patients to respond to those cycles because they have already shown us that they don't do well with chemotherapy — however some do respond and can go into complete remission."
The question then becomes whether patients at that point will fare better with CAR T or auto-HCT, and the results indicate that "auto-HCT gives those patients a pretty solid remission that looks better than [that with] CAR T therapy."
Dr. Shadman noted that the results serve to inform or confirm key clinical practices, including "in patients with late relapses, after 12 months, auto-HCT should remain the standard of care.
"In patients with primary refractory disease or early relapse, CAR T should be the goal of therapy and improving access to CAR T should remain a priority.
"In the subset of patients who achieve a CR with interim treatment, a discussion about the possibility of utilizing auto-HCT seems reasonable and can provide another curative option for some patients while keeping CAR-T as a backup treatment plan in case of auto-HCT failure."
Commenting on the study, Jonathan W. Friedberg, MD, the Samuel Durand Professor of Medicine and director of the Wilmot Cancer Institute, University of Rochester, New York, said, "these findings confirm utility of auto-HCT in patients who achieve a CR."
However, "the problem is that only a small fraction of patients achieve CR in this situation, and we do not know who they are going to be at time of relapse," he told this news organization.
He agreed that "given robust randomized trials showing overall survival benefit of CAR-T compared to auto-HCT in patients with high risk relapsed DLBCL, CAR-T treatment should remain the current standard.
"However, these current results help to confirm the strategy for management of low-risk (late) relapses and indicate that auto-HCT still has a place for these patients if they achieve CR with salvage therapy."
Dr. Shadman reported relationships with ADC therapeutics, Bristol Myers Squibb, Genmab, Lilly, Vincerx, Kite (Gilead), Janssen, Fate Therapeutics, MorphoSys/Incyte, AstraZeneca, BeiGene, Pharmacyclics, Mustang Bio, AbbVie, Genentech, MEI Pharma, Regeneron, and TG Therapeutics. Dr. Friedberg had no disclosures to report.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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