A view from the bridge to transplant for PTCL

LA JOLLA, CALIF. – For patients with relapsed peripheral T-cell lymphoma, allogeneic stem cell transplants offer the best chance for achieving remission or even a cure, making the choice of therapies as bridges to transplant essential for getting there.

“The goal is to get to transplant with a curative intent. In our hands, that’s mostly allo[geneic] and mostly in the relapsed setting,” Steven M. Horwitz, MD, from the lymphoma service at Memorial Sloan Kettering Cancer Center, New York, said at the annual T-cell Lymphoma Forum. “The best bridge to transplant is the one that gets you across safely.”

^{Courtesy Larry Young}

Dr. Steven M. Horwitz

“They’d finish ICE, get a 3- or 4-week break, get a transplant, leave the hospital 3 or 4 weeks later, and then usually by their first repeat scan, at least on average, those patients had already progressed, so we sort of cooled to the idea of auto transplant and started preferentially looking at allo if we were going to treat with curative intent in the relapsed setting,” he said.

In contrast to autologous SCT, the Memorial Sloan Kettering experience with allogeneic SCT for 65 patients with relapsed PTCL showed a 2-year overall survival rate of 59%, 2-year PFS rate of 48%, and a median PFS of 20.3 months. However, the rate of 1-year transplant-related mortality was still relatively high, at 17%, Dr. Horwitz acknowledged (ASH 2015. Abstract 4392).

An updated retrospective analysis of the center’s experience treating mature T-cell lymphoma patients with allogeneic SCT, also presented at the 2018 T-cell Lymphoma Forum, showed that disease status at transplant was one of the most important predictors of outcome. Median posttransplant PFS for patients in complete remission (CR) at the time of transplant was 61.3 months, compared with 11.4 months for patients in partial remission, 14 months for patients with stable disease, and 6.4 months for patients with disease progression (TCLF 2018. Abstract TM18_9).

“I think we can probably infer from [this] that CR not only gives you a better outcome with allo, but probably increases your chance that you get to an allo,” he said.

In the randomized phase 3 Lumiere study comparing the Aurora A kinase inhibitor alisertib with investigators’ choice of therapy in relapsed/refractory PTCL, alisertib was associated with a CR rate of 19%, whereas pralatrexate, gemcitabine, and romidepsin were associated with CR rates of 29%, 23%, and 33%, respectively, putting them on par with combination chemotherapy.

“I think many of us prefer some of the newer single agents because we’re really going for a durable maintenance of disease control rather than short-term bridge to transplant, but these drugs can provide adequate responses to transition over,” he said.

Better approaches by subtype?

The subtype of PTCL also appears to matter. Three approved agents for relapsed/refractory PTCL – belinostat (Beleodaq), romidepsin (Istodax), and pralatrexate (Folotyn) – are associated with CR rates of 11%, 15%, and 11%, respectively. But one PTCL subtype, anaplastic large cell lymphoma, appears particularly sensitive to treatment with brentuximab vedotin (Adcetris), with CR rates of 59%, Dr. Horwitz noted.

In a 2014 study, investigators reported that of the nine patients with anaplastic large cell lymphoma positive for anaplastic lymphoma kinase and treated with the anaplastic lymphoma kinase inhibitor crizotinib (Xalkori), all had a CR, with response durations stretching pasting 40 months in one patient, and past 30 months in two others (J Natl Cancer Inst. 2014 Feb;106[2]:djt378).

A different subtype, natural killer/T-cell lymphoma, was shown to be responsive to immunotherapy with pembrolizumab (Keytruda) in seven patients, with CRs in five and partial remissions in two. Responses to pembrolizumab in this PTCL subtype may be adequately long for getting patients to transplant, Dr. Horwitz said.

For some patients with angioimmunoblastic T-cell lymphoma, therapy with epigenetic modifying agents, such as decitabine or a combination of romidepsin and lenalidomide (Revlimid), with or without carfilzomib (Kyprolis), may also be effective bridges to transplant, based on the best available evidence.

Timing may also matter

Dr. Horwitz cautioned that for patients with cutaneous T-cell lymphoma, the investigational agent mogamulizumab, which was shown in the MAVORIC (Study of KW-0761 versus Vorinostat in Relapsed/Refractory CTCL) trial to offer significantly better PFS compared with vorinostat (Zolinza), also appears to increase the chance that patients will develop high-risk, potentially fatal graft vs. host disease posttransplant.