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T-cell lymphoma registries: What have we learned?


 

Registries for T-cell lymphoma have improved our understanding of the disease, but many questions remain. Could combining the various registries provide more answers?

“[T]here are many, many different registries around the world,” said Owen O’Connor, MD, PhD, of Columbia University, New York. “What’s now being floated in the field is, can we leverage all the different strengths of these different registries and try to compile them into a single registry where we can build the numbers of patients … to garnish a better insight into the natural history of the disease?”

Thus far, registries have highlighted the fact that T-cell lymphoma is difficult to treat, and it isn’t clear from registry data which treatments are most effective.

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Researchers still don’t know for certain if CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is less effective than CHOEP (CHOP plus etoposide), if novel single agents are more effective than combination chemotherapy, or if patients benefit from consolidation with autologous stem cell transplant (ASCT).

Chemo and single agents

Data from the U.S.-based COMPLETE registry suggested that patients with peripheral T-cell lymphoma (PTCL) have better overall survival (OS) if they receive anthracycline-based regimens upfront (Cancer. 2017 Apr 1;123[7]:1174-83).

However, the International T-cell Lymphoma Project suggested that anthracycline-containing regimens only improve outcomes in patients with ALK-positive anaplastic large-cell lymphoma. Patients with PTCL not otherwise specified or angioimmunoblastic T-cell lymphoma did not appear to benefit from anthracyclines (J Clin Oncol. 2008 Sep 1;26[25]:4124-30).

More recent data from the Czech NiHiL registry indicated that PTCL patients who receive CHOEP have longer progression-free survival (PFS) and OS than patients who receive CHOP (Ann Hematol. 2019 Aug;98[8]:1961-72). However, data from the Swedish Lymphoma Registry suggested CHOEP only provides a PFS benefit in PTCL patients aged 60 years and younger (Blood. 2014 124:1570-7).

Additional data from the COMPLETE registry suggested novel single agents might be more effective than combination chemotherapy, but the results aren’t clear. Data presented at the 2019 T-cell Lymphoma Forum showed that patients who received single agents had a significantly higher complete response rate and significantly longer PFS and OS than patients who received combination chemotherapy. However, data published in July 2019 showed no significant differences in overall response rate, PFS, or OS between the single-agent and combination groups (Acta Haematol. 2019 Jul 17. doi: 10.1159/000500666).

Both sets of COMPLETE data indicated that patients with refractory PTCL were less likely than those with relapsed disease to receive newer single agents. The data also showed that refractory patients had worse outcomes than patients with relapsed disease.

Role of ASCT

Data from the Swedish registry, Czech registry, COMPLETE registry (Cancer. 2019 May 1;125[9]:1507-17), and T-cell Project (Haematologica. 2018 Jul;103[7]:1191-7) all suggest ASCT is underutilized in patients with PTCL.

“If you look at the recommendations of the [National Comprehensive Cancer Network], patients should go to a transplant upfront if they have a complete response to chemotherapy,” said Francine Foss, MD, of Yale Cancer Center in New Haven, Conn. “It turned out, though, that only a small proportion – about 23%, 24% – of patients [in COMPLETE] actually went to a stem cell transplant. A higher number of patients with a complete response were followed without any subsequent therapy.”

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ASCT may be underused, in part, because it isn’t clear if the treatment provides a benefit in PTCL. Data from the Swedish registry and T-cell Project suggested ASCT can improve survival, but the Czech registry data showed no survival difference between ASCT recipients and nonrecipients.

Likewise, the COMPLETE registry showed no significant differences in median PFS and OS between ASCT recipients and nonrecipients. However, the data indicated that ASCT may provide a survival benefit in some patients, such as those with advanced disease.

Moving forward

There are several other registries from which researchers might gain insight into T-cell lymphoma. China (NCT03313271), Thailand, and Denmark (Clin Epidemiol. 2016;8:577-81) have registries open to all lymphoma patients. Brazil (NCT03207789) and South Korea (NCT02364466) have registries specific to T-cell lymphoma.

The Intercontinental Cooperative Non-Hodgkin T-cell Lymphoma Prospective Registry includes patients from China, Indonesia, Korea, Malaysia, Singapore, and Taiwan (NCT02691351).

The T-cell Project 2.0 is open to patients in Europe, South America, Asia, Australia, and the United States (https://www.tcellproject2.org/). This reboot of the T-cell Project has been adapted to accommodate advances in the field.

“This time, we’re including tissue for molecular studies, for genetic analysis, which is critically needed in this era of precision medicine,” Dr. Foss said. “Also, we’re going to be including PET scans and trying to determine whether or not the PET scans are predictive of response.”

Dr. Foss added that the COMPLETE registry has been closed because of a lack of funding, but she is trying to obtain funding to reopen it. In the meantime, U.S. patients can enroll in the T-cell Project 2.0.

Dr. Foss oversees the COMPLETE registry, which was funded by Spectrum Pharmaceuticals. She has contributed to the T-cell Project and T-cell Project 2.0, both funded by Associazione Angela Serra per la ricerca sul cancro. Dr. O’Connor reported having no relevant disclosures.

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