Expert Shares Insight on Developments in T-Cell Lymphoma

Jonathan Brammer, MD

The treatment landscape for patients with T-cell lymphoma continues to evolve, with ongoing advances that include the utilization of brentuximab vedotin (Adcetris), according to Jonathan Brammer, MD.

Findings from the phase III ALCANZA trial, which investigated brentuximab vedotin compared with physician’s choice of standard treatment, were the basis for the FDA’s decision to grant the therapy a priority review designation for patients with cutaneous T-cell lymphoma.

The median progression-free survival (PFS) was 16.7 months with brentuximab vedotin versus 3.5 months with physician’s choice of therapy (HR, 0.270; 97% CI, 0.169-0.430; P <.0001). The objective response rate (ORR) was 67% versus 20% (P <.0001), with complete response (CR) rates of 16% versus 2% (P = .0046) in the brentuximab vedotin and control arms, respectively.

OncLive: Can you provide an overview of your presentation on T-cell lymphoma?

In an interview with OncLive^® at the 2017 State of the Science Summit^TM on Hematologic Malignancies, Brammer, a hematologist at The Ohio State University Comprehensive Cancer Center, discussed exciting therapeutic developments for patients with T-cell lymphoma.Brammer: T-cell lymphomas have been an area of limited progress and poor overall prognosis. Over the past several years, we’ve had some exciting new developments. One of the most exciting developments is brentuximab vedotin, which is now being utilized for patients with relapsed CD30-positive anaplastic large cell lymphoma, some of whom have long-term durable remissions. Brentuximab vedotin is also highly effective in patients with relapsed cutaneous T-cell lymphoma, as well.

Beyond that, we reviewed many different treatments available for relapsed peripheral T-cell lymphoma. One of my preferred agents is the histone deacetylase (HDAC) inhibitors, such as romidepsin (Istodax). Another HDAC inhibitor on the market is belinostat, which is also effective. These agents have demonstrated 15% CR rates. In my opinion, they are good agents to be used rather than standard ICE [ifosfamide, carboplatin, and etoposide] or DHAP [dexamethasone, high-dose cytarabine, and cisplatin] chemotherapy.

Can you discuss some ongoing trials with checkpoint inhibitors in this landscape?

Additionally, bendamustine appears to be a very effective chemotherapy regimen that I'm using in my clinical practice in patients with relapsed T-cell lymphoma who have failed on an HDAC inhibitor, brentuximab vedotin, or have relapsed after an autologous stem cell transplant. I find that I can get durable remissions in those patients. On the horizon, I see a lot of new exciting therapies emerging in T-cell lymphomas. At the 2017 ASH Annual Meeting, researchers presented an abstract looking at pembrolizumab (Keytruda) in patients with cutaneous T-cell lymphoma who had relapsed disease. Some of these patients had relapsed 4 to 6 times with cutaneous T-cell lymphoma. While it was only a small number of 24 patients, there were some significant responses; most were partial responses, but there were also some CRs.

Are there any remaining questions that still exist with brentuximab vedotin?

Moving forward, PD-1 inhibitors will be investigated in cutaneous T-cell lymphoma. Unfortunately, for patients with peripheral T-cell lymphoma, single-agent PD-1 therapy seems to have a modest benefit of a 15% to 20% response rate; however, combination trials may prove fruitful in the future.The question that we are discussing is whether patients with CD30-positive anaplastic large cell lymphoma can achieve long-term remissions. Is there a need for a transplant in patients who have not received transplant? That question will not be answered anytime soon because of the rarity of disease, but it remains to be an important question.

Another question is, is brentuximab vedotin effective in the frontline setting? There is a clinical trial looking at brentuximab vedotin combined with standard CHOP therapy for anaplastic large cell lymphoma omitting vincristine because of the associated neuropathy. Whether brentuximab vedotin can be moved to the frontline setting as it has been in Hodgkin lymphoma is an ongoing question that is being investigated.

What are the remaining challenges that still exist for patients with T-cell lymphomas?

Brentuximab vedotin does seem to have some efficacy and preliminary studies in other CD30-positive T-cell lymphomas. The question is, how effective is brentuximab vedotin in the long-term for patients with relapsed CD30-positive T-cell lymphoma that is not of either cutaneous T-cell or anaplastic large cell histology?The biggest challenge with T-cell lymphomas is the high rate of disease relapse in frontline therapy, even after autologous stem cell transplant. Long-term cure is only achieved in about 35% of patients, or perhaps 50% if you add an autologous stem cell transplant.

What does the future of this landscape look like?

Even with new and emerging exciting therapies, aside from allogenic transplant in the relapsed/refractory setting, we don't have good long-term options. Identification of the genetic pathologic subtypes and how they differ and vary in response are going to become increasingly important in T-cell lymphoma so that we can intelligently target this disease. In the next 5 to 10 years, we are going to have a much better understanding of the genetic and epigenetic landscape of T-cell lymphomas. We’re going to see even more provisional T-cell lymphoma diagnoses with the 2024 pathologic criteria. Amongst that, there are certain diseases that are going to respond to certain genetic signatures or certain subtypes of T-cell lymphoma. Increasingly, targeted drugs in T-cell lymphoma, such as brentuximab vedotin, are going to become increasingly important as we identify new targets and genetic apparitions in these lymphomas.

Prince HM, Kim YH, Horwitz SM, et al. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial [published online June 6, 2017]. Lancet. 2017;390(10094):555-566. doi: 10.1016/S0140-6736(17)31266-7.