Best Uses of Transplantation for Patients With Peripheral T-Cell Lymphoma

Randomized studies examining patients with peripheral T-cell lymphoma regarding the role of transplant are lacking and more research is needed to personalize therapy for patients based on subtype, biomarkers, mutational profiling, and radiographic parameters.

Patients with peripheral T-cell lymphoma (PTCL) who can achieve sufficient disease control will benefit most by autologous stem cell transplantation in first remission and allogeneic stem cell transplantation in relapsed disease vs chemotherapy alone.1

For patients with PTCL, treatment decisions are supported mostly by phase 2 studies, retrospective series, and expert opinion, according to a study published in Springer Link.

Though cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (CHOP) is often used in patients with PTCL, the addition of brentuximab vedotin (Adcetris) has bested the CHOP regimen, showing meaningful improvement in progression-free survival (PFS) and overall survival (OS).

“Overall, randomized controlled trials in PTCL regarding the role of transplant are lacking…While the backbone of induction remains CHOP-like chemotherapy, the incorporation of brentuximab vedotin to frontline treatment algorithms will continue to improve outcomes for patients with ALCL,” wrote study authors led by Nicole C. Foley, Department of Medicine, Division of Oncology at Washington University School of Medicine in St. Louis.

PTCLs are a rare subset of non-Hodgkin’s lymphomas treated with curative intent. Patients with PTCL have treatments which are based on those of other aggressive lymphoid malignancies. However, outcomes for these patients are generally poorer with 5-year OS of 30%-40% and PFS of 20%-30%, respectively.

Generally, PTCL is treated using combination therapy and patients are often required to have evaluations. Patients with more common histologies and those who are chemoresponsive can be considered for an autologous transplant in first remission. Now, investigators have started using transplantation for these patients in both the frontline and salvage settings to improve outcomes.

Although their prognosis is still poor, patients with relapsed/refractory PTCL who have an allogeneic transplant may end up having a durable remission.

For years, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone [CHOP] with or without etoposide [CHOEP] has been a standard of care for this patient population. With these combinations, the overall response rate demonstrated in patients has been approximately 80% with complete response rates between 40%-50%. Still, most patients relapse. In this setting, allogeneic transplant remains the only curative option for patients who are transplant eligible.

Then, 5-year results from the ECHELON-2 trial demonstrated a survival benefit. In the double-blind, randomized study, a meaningful improvement in progression-free survival (PFS) and OS was seen in patients with CD30-positive PTCL when treated with a regimen of brentuximab vedotin (Adcetris) plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) vs CHOP.

In the trial, 452 patients were randomized 1:1 to receive 6 or 8 cycles of A+CHP (n= 226) or CHOP (n = 226). At a median follow-up of 47.6 months, the 5-year PFS rate was 51.4% (95% CI, 42.8%-59.4%) in the A+CHP arm compared with 43.0% (95% CI, 35.8%-50.0%) in the CHOP arm (hazard ratio [HR] = 0.70; 95% CI, 0.53-0.91; P = .0077). For patients treated with A+CHP, the 5-year OS rate was 70.1% (95% CI, 63.3%-75.9%) vs 61.0% (95% CI, 54.0%-67.3%) in patients treated with CHOP (HR = 0.72; 95% CI, 0.53-0.99).

In the A+CHP arm, the median PFS was 62.3 months (95% CI, 42.0-not evaluable) vs 23.8 months (95% CI, 13.6-60.8) for the CHOP arm. The estimated 5-year PFS for patients with systemic anaplastic large cell lymphoma (sALCL) was 60.6% (95% CI, 49.5%-69.9%) for A+CHP compared with 48.4% (95% CI, 39.6%-56.7%) for CHOP (HR = 0.55; 95% CI, 0.39-0.79; P = .0009). The median OS was not reached in either arm.

Further, patients with angioimmunoblastic T-cell lymphoma (AITL) derived a greater benefit with standard CHOP chemotherapy compared with what has been reported in previous studies. Patients with AITL treated with CHOP had estimated 5-year OS and PFS rates of 62.5% and 48%, respectively. These data were superior to those in the PTCL-NOS subgroup of patients who were treated with CHOP as their 5-year OS and PFS rates were 36% and 26%.

Since this study, additional agents, including alemtuzumab (Lemtrada), romidepsin (Istodax), and lenalidomide (Revlimid), have been examined in combination with an upfront CHOP-based therapy. However, each of these trials have resulted in negative outcomes. Investigators now are looking to improve upon the CHOP and CHOEP regimens by adding hypomethylating agents of PI3K inhibitors to the mix.

For patients with PTCL who are responsive to chemotherapy, consolidation with high-dose therapy and autologous stem cell transplantation at the time of first remission is considered the best option. If a patient has ALK plus ALCL, consolidation with autologous stem cell transplant is not recommended, according to various prospective and non-randomized trials.

Additionally, multiple series have now shown that 3-year overall survival with allogeneic transplant is approximately 60%. Patients with AITL demonstrated better outcomes compared with non-AITL histologies when having an allogeneic transplant.

Retrospective studies which directly compared outcomes of patients who had received autologous stem cell transplant and allogeneic stem cell transplant in the relapsed/refractory setting found there to be little to no relative benefit with allogeneic over autologous as the value from the graft-vs-lymphoma effect was offset by the increased treatment-related mortality (TRM). In this study, the 3- to 5-year TRM ranged from 33%-40% with allogeneic stem cell transplant and 6%-17% with autologous stem cell transplant.

Through examining a plethora of studies, findings indicate that autologous stem cell transplantation can induce durable and possibly curative remissions for select patients with PTCL. Yet, only about 2/3 of patients can go on to high-dose therapy and autologous stem cell transplant.

While the International Prognostic Index (IPI) continues to define risk groups for patients with PTCL, it is noted that treatment approaches should not be tailored to IPI scores as even patients with low-risk disease have poor outcomes when given intensive treatment. Because of this, investigators are also finding strategies to evaluate the use of mutational profiling, cell-free DNA, and minimal residual disease monitoring to help certain patients.

Overall, randomized studies examining patients with PTCL regarding the role of transplant are lacking. In multiple studies, similar results regarding the use of autologous stem cell transplant in the first remission have been shown with about a 20% improvement in PFS and OS compared with those not treated with an intent to transplant approach.

Though progress is being made, more understanding in this area of lymphoma research is needed. With the increase of data suggesting various needs for the different histologies of PTCL, the future hopes to personalize therapy for patients based on subtype, biomarkers such as minimal residual disease, mutational profiling, and radiographic parameters.

“Given that we have limited tools to help select patients for transplant, organizations have suggested universally offering consolidative transplants for eligible patients in first remission. Unfortunately, most patients with PTCL will relapse after induction or be refractory for initial therapy. For these patients, the best hope of long-term survival is achieving disease control and then proceeding to [allogeneic stem cell transplant],” concluded the study authors.

REFERENCE:
Foley NC, Mehta-Shah N. Management of peripheral T-cell lymphomas and the role of transplant. Curr Oncol Rep. 2022;24(11):1489-1499. doi:10.1007/s11912-022-01310-3