ASCT Tops CAR T-Cell Therapy for Relapsed LBCL in Complete Remission

— Better 2-year PFS, OS, however now not appropriate to main refractory disease

by
Charles Bankhead, Senior Editor, MedPage This day
December 10, 2023

SAN DIEGO — Autologous stem-cell transplantation (ASCT) resulted in improved outcomes as compared with CAR T-cell treatment for sufferers with relapsed immense B-cell lymphoma (LBCL) in total remission, a retrospective prognosis confirmed.

Patients who underwent ASCT had fewer relapses at 2 years (27.8% vs forty eight.0%) and higher progression-free survival (PFS, 66.2% vs 47.8%), and total survival (OS, 78.9% vs 65.6%). In the subgroup of sufferers with early cure failure, ASCT used to be linked to a decrease 2-year relapse rate (22.8% vs forty five.9%). Treatment-linked mortality did now not vary between the two sorts of cure.

By multivariate prognosis, CAR T-cell treatment used to be linked to a elevated menace of relapse and rotten PFS, reported Mazyar Shadman, MD, of the College of Washington and Fred Hutchinson Cancer Heart in Seattle, at the American Society of Hematology (ASH) assembly.

“The message right here is that this info would possibly furthermore very successfully be practice informing and confirming,” Shadman said within the course of an ASH press briefing. “In sufferers who relapse after first-line treatment after 300 and sixty five days, the recent long-established of care is salvage treatment with autotransplant. This info confirms that. There would possibly be for the time being no info suggesting that sufferers who’re in CR [complete remission] will like to acquire CAR-T treatment in that surroundings.”

“The plan of treatment must be CAR-T treatment, and all efforts must be made to make stronger get entry to to CAR-T,” he persevered. “Till then, for sufferers who discontinue a legit scientific response, an autotransplant [ASCT] plan normally is an cheap possibility to chat about … and will add every other doubtlessly healing treatment for these sufferers, sparkling that CAR-T would possibly furthermore aloof be utilized within the later line of treatment if autotransplant fails the affected person.”

LBCL in CR

For the length of a discussion that followed the presentation, Shadman emphasised that the ask fervent sufferers who were in CR after initial relapse. Patients referred for CAR T-cell treatment continually obtain chemotherapy within the course of the interval when cells are being processed for infusion.

“We don’t demand these sufferers to answer to subsequent chemotherapy on yarn of they’ve already confirmed that they do now not enact successfully with chemotherapy,” he said. “Nevertheless, some enact. Once rapidly we seek after one or two cycles of chemotherapy, their disease goes away. They’re in total remission.

“The [situation raises] a useful attach a question to. This affected person has very chemo-comely disease. Everyone knows that they enact successfully with autotransplant, so what’s going to we enact now? Unruffled send them for CAR-T? Presumably are trying autotransplant on yarn of all americans knows they’ll furthermore very successfully be cured with autotransplant, and if autotransplant doesn’t work, you proceed to love CAR-T as your backup conception.”

For sufferers with main refractory disease, CAR T-cell treatment is the cure of assorted in second line.

“We are now not suggesting that these sufferers must be despatched for autotransplant,” said Shadman.

The discussion resulted in feedback about the FDA’s recent security dialog concerning a doable menace of secondary malignancies with CAR T-cell treatment.

“Develop you judge extra of these CAR T-cell-linked malignancies will emerge and is that extra justification for pivoting towards autologous transplant in these sufferers?” requested press briefing moderator Mikkael Sekeres, MD, of the College of Miami Sylvester Comprehensive Cancer Heart.

Shadman said he and varied CAR T-cell investigators know puny about the difficulty beyond what the FDA has communicated.

“The different of secondary cancers that will likely be staunch now linked to CAR-T is amazingly low when compared with the aid that CAR-T gives in curing a in point of fact excessive percentage of sufferers who do now not need any varied options,” said Shadman. “I don’t reflect that the label — which is terribly indispensable and must be followed and will likely be followed — will change the rest in our practice in offering healing treatment for relapsed lymphoma.”

High-dose chemotherapy, continually frail alongside with ASCT, is also linked to secondary malignancies, he added.

Background, Key Findings

CAR T-cell treatment has turn out to be long-established of cherish relapsed LBCL as early as second line. In scientific practice, get entry to to CAR T-cell treatment would possibly furthermore very successfully be delayed ensuing from logistical points, and within the intervening time, sufferers would possibly furthermore obtain bridging chemotherapy. A couple of of the sufferers discontinue a partial or total response. Several reports like confirmed that CAR T-cell treatment is security and active in sufferers who discontinue a total response with bridging treatment, said Shadman.

Furthermore, Shadman and colleagues recently reported the superiority of ASCT over CAR T-cell treatment in sufferers with LBCL in partial remission.

The observations supplied the premise for a retrospective comparison of outcomes with ASCT and CAR T-cell treatment in sufferers with LBCL in CR. Investigators hypothesized that transplant would be superior in that surroundings.

Files for the ask came from the Heart for Worldwide Blood & Marrow Transplant Research registry. The prognosis incorporated adults with diffuse LBCL in CR, handled with CAR T-cell treatment from 2018-2021 (n=seventy nine) or ASCT from 2015-2021 (n=281). Median apply-up used to be 24.7 months for CAR-T and 49.7 months for ASCT. Essentially the most indispensable endpoints were PFS and OS.

The implications appreciated ASCT for most outcomes:

• 2-year PFS: 66.2% vs 47.8% (P<0.001)
• 2-year OS: 78.9% vs 65.6% (P=0.037)
• Relapse/progression: 27.8% vs forty eight% (P<0.001)
• Nonrelapse mortality: 5.9% vs 4.1% (P=0.673)

An prognosis of a subgroup of about 240 sufferers with early relapse (inner 300 and sixty five days) after first-line treatment also appreciated ASCT for PFS (68.2% vs forty eight.4%, P=0.001) and relapse/progression (25% vs 46.3%, P<0.001). Survival trended in desire of ASCT (seventy nine.6% vs 66.3%, P=0.131), and nonrelapse mortality did now not vary drastically (6.8% vs 5.3%, P=0.771).

A multivariable prognosis confirmed that CAR T-cell treatment used to be linked to drastically rotten PFS (HR 1.83, 95% CI 1.27-2.63, P=0.0011) and relapse/progression (HR 2.18, 95% CI 1.forty eight-3.20, P<0.0001).

Shadman acknowledge so a lot of limitations of the prognosis: lack of skill to dispose of doable confounders; need for a randomized trial to overview CAR-T and ASCT in sufferers with LBCL in CR; and disclose of tisagenlecleucel (Kymriah) in a majority of sufferers, which can furthermore like resulted in underestimation of the efficacy of CAR T-cell treatment.