Allogeneic Transplant: Durable Remissions in
T-Cell Lymphomas

Andrew D. Bowser

December 08, 2020

In patients with T-cell lymphoma, allogeneic transplant can lead to durable remissions among patients who might otherwise have poor outcomes, results of a large retrospective observational study suggest.

Five-year progression-free survival (PFS) approached 40% and 5-year overall survival (OS) was over 50% in the study, which according to an investigator is the largest-ever reported patient series of allogeneic stem cell transplantation in T-cell lymphomas.

"We believe that eligible patients with relapsed/refractory T-cell lymphomas should be considered for consultation for allogeneic transplant by an expert clinician," said investigator Neha Mehta-Shah, MD, of Washington University in St. Louis.

"These decisions should occur on a patient by patient level — but it's important to consider this," Mehta-Shah said at the annual meeting of the American Society of Hematology, held virtually this year.

Notably, patients with cutaneous T-cell lymphoma (CTCL) had a higher rate of relapse yet similar overall survival (OS) compared to patients with common peripheral T-cell lymphoma (PTCL) subtypes, according to Mehta-Shah.

Among PTCL subtypes, there was a trend toward improved PFS and OS for angioimmunoblastic T-cell lymphoma (AITL), compared with PTCL not otherwise specified (PTCL-NOS) and anaplastic large-cell lymphoma (ALCL), she added.

Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone's Perlmutter Cancer Center, said the results of this retrospective study need to considered in light of the treatment-related risks associated with allogeneic transplantation.

Treatment-related mortality in the study ranged from about 8% to 24%, depending on the donor type, while acute and chronic graft-versus-host-disease (GvHD) was seen in more than 40% of patients, the reported data show.

"If I have a relapsed patient with AITL, I would look to this data and say that patients with AITL appear in a retrospective study to have a strong benefit," Diefenbach said in an interview.

"For the other patients, you would describe both potential benefits and also discuss the treatment-associated risks – both the chronic GvHD and transplant-related mortality – and you'd have to balance the risk with the benefits for each individual case," Diefenbach added.

The retrospective analysis by Mehta-Shah and colleagues included 508 consecutive T-cell lymphoma patients receiving allogeneic transplants at 12 academic centers between 2000 and 2019. The most common subtypes were PTCL-NOS in 26%, AITL in 16%, CTCL in 13%, and hepatosplenic T-cell lymphoma (HSTCL) in 7%. About 40% had a matched related donor (MRD) and 39% had a matched unrelated donor (MUD). The conditioning regimen was myeloablative in about a third of patients and nonmyeloablative in two-thirds.

At 5 years, PFS was 39.4% and OS was 50.8% for the overall study cohort, Mehta-Shah reported, noting that the median time from relapse to death post allogeneic transplant was 10.2 months.

Patients in complete remission at the time of transplant fared better than others, with a median PFS of 44.6 months vs. 8.5 months for those in partial remission, 21.0 months in those with stable disease, and 3.5 months for those with progressive disease at time of transplant, data show.

Patients with common PTCL subtypes had better PFS compared to patients with CTCL, yet OS was similar, according to the investigator. At 5 years, PFS was 43.7% and 18.6%, respectively, for PTCL and CTCL, while OS was 53.1% and 44.0%, respectively.

There was a trend toward improved outcomes for AITL relative to PTCL-NOS and ALCL, with a median PFS of 51.4 months for AITL versus 18.3 months those other subtypes. Similarly, median OS was not reached for AITL versus 73.1 months in the other subtypes.

Treatment-related mortality was lowest for patients with MRDs, or 8.2% at 12 months, Mehta-Shah reported, while patients with MUDs, mismatched donors, or haploidentical donors had treatment-related mortality of 13% to 16% at 12 months, and those with cord blood donors had treatment-related mortality of nearly 24% at 12 months.

Acute GvHD was observed in 46% of patients and chronic GvHD was seen in nearly 41%, the investigator added.

While these findings are important to consider in individual patient consultations, the study is nevertheless subject to limitations including patient selection and referral bias, according to Mehta-Shah.

"This was a retrospective analysis of patients who underwent transplant," she said in a question-and-answer period. "Of course, that is heavily biased by who got to a transplant center, who was well enough to achieve transplant, and who had a donor or donor options, as well as their overall health and depth of remission," the researcher said.

"I think this just represents what we could tell patients about what may happen to them once they embark on a transplant," she added, "but really, there would be more prospective work needed to be done for what happens to patients overarching, and how many of them even get to a transplant consultation."

Further studies should be done to develop predictive tools or biomarkers to determine who benefits from an allogeneic transplant, if there are predictors of relapse following allogeneic transplant, and what are the mechanisms of relapse following allogeneic transplant, according to Mehta-Shah.

Mehta-Shah reported research funding from Bristol Myers-Squibb, Celgene, Verastem, Corvus, Innate Pharmaceuticals, and Genentech/Roche. She reported consultancy with Kyowa Hakko Kirin, C4 Therapeutics, and Karyopharm Therapeutics.

SOURCE: Mehta-Shah N et al. ASH 2020, Abstract 41.

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