AVAHO Regional Meeting Addresses Complex World of Peripheral T-Cell Lymphoma

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.