ASH 2019 Data Cement Current Treatment Approaches in Hodgkin, T-Cell Lymphoma

Weiyun Z. Ai, MD, PhD

Research presented at the 2019 ASH Annual Meeting provided confirmatory data for current treatment strategies in peripheral T-cell lymphoma (PTCL) and Hodgkin lymphoma, according to Weiyun Z. Ai, MD, PhD, a clinical professor of medicine in the Department of Medicine at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.

For example, data from the phase III ECHELON-2 trial previously showed that brentuximab vedotin (Adcetris) plus CHP (cyclophosphamide, doxorubicin, prednisone; A+CHP) versus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) led to a 29% reduction in the risk of disease progression or death (HR, 0.71; 95% CI, 35.2 to not evaluable [NE]; P = .0110) and a 34% reduction in the risk of death (HR, 0.66; 95% CI, 0.46-0.95; P = .0244) in previously untreated patients with CD30-positive PTCL.¹ Data from the trial served as the basis for the regimen’s approval in this indication in November 2018.

According to a post hoc analysis presented at the 2019 ASH Annual Meeting, patients who achieved a complete response (CR) with A+CHP may still derive benefit from transplant. Among 27 patients with systemic anaplastic large-cell lymphoma (ALCL) who received A+CHP, the median progression-free survival (PFS) was not reached with transplant (95% CI, 36.57 to NE) versus 55.66 months without (95% CI, 23.72-55.66).²

“Previously, I may not have taken patients who did well with A+CHP to transplant,” said Ai. “That may have been a premature decision. I believe that transplant will continue to play a role until we have more definitive data.”

In the field of Hodgkin lymphoma, brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) became a standard frontline option for patients with newly diagnosed, advanced-stage classical Hodgkin lymphoma, according to findings from the phase III ECHELON-1 trial. According to data from the primary analysis, A+AVD led to a 23% reduction in the risk of progression or death versus doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD; HR, 0.77; 95% CI, 0.60-0.98; P = .04);³ this percentage grew to 31% after a median follow-up of 48.4 months (HR, 0.69; 95% CI, 0.542-0.881; P = .003), according to updated data presented at the 2019 ASH Annual Meeting.⁴

“At the 2019 ASH Annual Meeting, we saw data in T-cell lymphoma and Hodgkin lymphoma that really validated previous data we had seen,” said Ai. “We also have more data to provide our patients with, in the absence of definitive clinical trials.”

In an interview during the 2019 OncLive^® State of the Science Summit™ on Hematologic Malignancies, Ai discussed some of the most pivotal advances that have been made in the fields of T-cell lymphoma and Hodgkin lymphoma in recent years.

OncLive: What are some of the recent developments that have been made in T-cell lymphoma?

Ai: In T-cell lymphoma, many agents are in the pipeline, the most notable of which include the PI3K isoform—selective inhibitors and other JAK/STAT pathway inhibitors. [Treatment approaches are becoming] more targeted. Biomarkers can predict responses in certain situations, which is really exciting. That’s the direction we’re heading.

The most practice-changing study we have seen in recent years is the phase III ECHELON-2 trial. In the trial, patients with untreated CD30-positive PTCL were randomized to receive either CHOP or A+CHP. A+CHP showed superior PFS and overall survival (OS) versus CHOP. This was the first time we saw an OS improvement in T-cell lymphoma. The improvement in OS with A+CHP translated to about a 30% reduction in the risk of progression or death.

Could you expand on the ECHELON-2 trial and the updated data presented at the 2019 ASH Annual Meeting? Do any questions remain?

When ECHELON-2 was first presented [at the 2018 ASH Annual Meeting] and we saw a benefit in PFS and OS with A+CHP, we questioned whether patients who achieved a CR needed to go to consolidation transplant. The more effective the induction therapy, the harder it is to see a benefit with consolidation therapy. At the 2019 ASH Annual Meeting, we saw research that evaluated the impact of transplant on the outcomes of patients in the trial. The study excluded patients with ALK-positive ALCL because they do very well without transplant. This was a post hoc analysis, so the study was not really powered to answer this question definitively. Nonetheless, I believe that it's a practical question. The analysis showed an improvement in PFS with transplant in patients who achieved a CR after receiving up-front A+CHP.

You also gave a presentation on Hodgkin lymphoma at the State of the Science Summit™. Could you discuss the 3-year update of the ECHELON-1 trial?

ECHELON-1 was a randomized phase III study in patients with untreated, advanced-stage disease. In the trial, patients were randomized to receive either ABVD or A+AVD. PFS favored the use of A+AVD. If you look at the forest plot, you also see the advantage of A+AVD in most subgroups. The 2-year landmark analysis [was published] in the New England Journal of Medicine. Since then, we’ve seen the 3-year report and 4-year follow-up, which was presented at the 2019 ASH Annual Meeting. The results are very consistent. We saw a durable benefit that continued to favor A+AVD versus ABVD in patients with advanced-stage disease.

Were any other trials presented at the 2019 ASH Annual Meeting that you found particularly exciting?

In Hodgkin lymphoma, the data with brentuximab vedotin plus the PD-1 inhibitor nivolumab (Opdivo) were exciting. That regimen was tested as first salvage therapy in a highly relapsed/refractory patient population. Patients in first relapse generally do not do well. In the study, approximately 42% of patients were refractory to first-line therapy. This is a high-risk population, but we saw great responses. A great number of patients were able to go onto transplant. There [was an impressive] 2-year PFS in patients who underwent transplant. In the intent-to-treat population, the results were still quite good with an [encouraging 2-year PFS]. Compared with historical rates, the results were quite spectacular. The same regimen was also tested as frontline therapy in elderly patients. I believe that it’s a highly active combination. However, we need to watch out for some toxicities and we need to learn how to manage them early.

References

1. Horwitz S, O’Connor OA, Pro B, et al; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised phase 3 trial. Lancet. 2019;393(10168):229-240. doi: 10.1016/S0140-6736(18)32984-2.
2. Savage KJ, Horwitz SM, Advani RH, et al. An exploratory analysis of brentuximab vedotin plus CHP (A+CHP) in the frontline treatment of patients with CD30+ peripheral T-cell lymphomas (ECHELON-2): impact of consolidative stem cell transplant. Blood. 2019;134(suppl 1; abstr 624):464. doi: 10.1182/blood-2019-122781.
3. Connors JM, Jurczak W, Straus DJ, et al; ECHELON-1 Study Group. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma [published correction appears in N Engl J Med. 2018;378(9):878. doi: 10.1056/NEJMx180007]. N Engl J Med. 2018;378(4):331-344. doi: 10.1056/NEJMoa1708984.
4. Bartlett NL, Straus DJ, Dlugosz-Danecka M, et al. Brentuximab vedotin with chemotherapy for stage 3/4 classical Hodgkin lymphoma (cHL): 4-year update of the ECHELON-1 study. Blood. 2019;134(suppl 1; abstr 624):4026. doi: 10.1182/blood-2019-124116.