Our Team’s Take on the Most Influential ASH 2018 Lymphoma Research

At the end of each year, the American Society of Hematology (ASH) Annual Meeting & Exposition brings together over 25,000 hematology professionals from around the world to discuss the latest research into the treatment of blood diseases. Highlights of ASH is a two-day program designed to update clinicians and researchers unable to attend the Annual Meeting with the findings most likely to impact daily clinical practice.

Our Lymphoma Program Chief, Dr. Peter Martin was selected to represent the Highlights of ASH Lymphoma Committee for a post-meeting update in January 2019. Here’s his take on the latest lymphoma research.

Diffuse Large B-Cell Lymphoma (DLBCL)

According to the FLYER study, patients younger than 60 with low-risk diffuse large B-cell lymphoma (DLBCL) had excellent outcomes with a shortened regimen of four cycles of R-CHOP chemotherapy versus the standard six cycles. The reduction in chemotherapy may allow for minimizing potential toxic side effects for this patient population.

Our Team’s Take
It is now clear that most young people with stage 1, low-risk DLBCL can be effectively treated with just four cycles of R-CHOP, but providers should use caution in extrapolating these results to rarer subtypes of DLBCL (e.g., primary mediastinal B-cell lymphoma, transformed lymphomas, etc.) that may not have been included in large numbers in the FLYER trial.

SOURCE 781- Excellent Outcome of Young Patients (18-60 years) with Favourable-Prognosis Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 4 Cycles CHOP Plus 6 Applications of Rituximab: Results of the 592 Patients of the Flyer Trial of the Dshnhl/GLA

R-CHOP chemotherapy is the standard treatment for people with previously untreated DLBCL. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has shown activity in people with a subtype of DLBCL known as non-germinal center B cell DLBCL (non-GCB DLBCL) whose disease has relapsed following treatment. The phase III PHOENIX trial examined whether adding ibrutinib to R-CHOP would improve treatment efficacy in previously untreated non-GCB DLBCL patients. Results demonstrated that R-CHOP plus ibrutinib was equivalent to R-CHOP alone. The study did note, however, that ibrutinib may provide some benefit in patients older than 60.

Our Team’s Take
For now, R-CHOP remains the gold-standard for most people with DLBCL, including non-GCB DLBCL. That said, it appears that BTK inhibitors have the potential to improve outcomes if the optimal patient population can be identified.

SOURCE 784 – A Global, Randomized, Placebo-Controlled, Phase 3 Study of Ibrutinib Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (RCHOP) in Patients with Previously Untreated Non-Germinal Center B-Cell-like (GCB) Diffuse Large B-Cell Lymphoma (DLBCL)

Follicular Lymphoma

Our own Dr. John Leonard led the global phase III AUGMENT clinical trial comparing the efficacy and safety of combined lenalidomide plus rituximab versus rituximab alone in people with previously treated indolent lymphoma, including follicular and marginal zone lymphoma. Lenalidomide-rituximab treatment resulted in superior progression-free survival (PFS) and overall survival (OS) outcomes when compared to rituximab treatment alone, representing an important new treatment option for this patient population.

Our Team’s Take
The impressive overall survival benefit seen in the AUGMENT trial implies that single-agent rituximab may no longer be appropriate for some people with previously treated follicular lymphoma.

SOURCE 445 – AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) Vs Rituximab/Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

Hodgkin Lymphoma

A currently accepted standard of care treatment for early-stage low-risk Hodgkin lymphoma is two cycles of ABVD chemotherapy followed by radiotherapy. In the HD16 trial examining the possibility of omitting radiotherapy from the treatment regimen, investigators found that two cycles of ABVD alone does not provide adequate disease control.

Our Team’s Take
A primary goal of cancer care is to deliver a maximally effective treatment regimen while sparing patients from excessive treatment-related side effects. Yet, this research demonstrates that two cycles of ABVD alone does not provide sufficient control of early-stage, favorable risk classical Hodgkin lymphoma. Outside of clinical trials, providers should consider either the addition of radiation or additional chemotherapy.

SOURCE 925 – PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase 3 Trial HD16 By the German Hodgkin Study Group)

T-Cell Lymphoma

Following the positive results of a phase I trial combining brentuximab vedotin (BV) with CHP (CHOP chemotherapy minus vincristine) in frontline treatment of T-cell lymphoma, researchers tested the combination in patients with newly diagnosed CD30+ anaplastic large cell lymphoma (ALCL), a type of T-cell lymphoma, in the ECHELON-2 trial. Brentuximab vedotin plus CHP was shown to produce better outcomes than standard CHOP for these patients.

Our Team’s Take
BV-CHP represents a new standard of care for anaplastic large cell lymphoma (ALK-positive and ALK-negative). It is less clear that BV adds significantly to CHOP in non-ALCL T-cell lymphomas regardless of CD30 status.

SOURCE 997 – The ECHELON-2 Trial: Results of a Randomized, Double-Blind, Active-Controlled Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in the Frontline Treatment of Patients with CD30+ Peripheral T-Cell Lymphomas

BONUS: Chimeric Antigen Receptor (CAR) T Cell Update

Multiple observational studies suggested that commercial, FDA-approved CAR T cell products used as part of standard practice resulted in outcomes that were comparable to outcomes seen in clinical trials prior to the approval of CAR T cells. Even patients with characteristics that might have resulted in exclusion from clinical trials (e.g., low blood counts) appeared to have comparable outcomes.

Our Team’s Take
CAR T cells clearly have a role in people with treatment-refractory DLBCL. Nonetheless, more research will be required to further improve the efficacy and safety of CAR T cells so that patients outside of academic medical centers might have access to this new treatment approach.

SOURCE 91 – Axicabtagene Ciloleucel (Axi-cel) CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: Real World Experience; 92 – Axicabtagene Ciloleucel in the Real World: Outcomes and Predictors of Response, Resistance and Toxicity

 

Novel Therapy Approved for Previously Untreated Hodgkin Lymphoma Patients

The United States Food and Drug Administration (FDA) recently approved brentuximab vedotin in combination with chemotherapy as a first-line treatment for people with advanced-stage classical Hodgkin lymphoma.

Also known as Adcetris, brentuximab vedotin is an antibody drug conjugate that targets the CD30 protein present on lymphoma cells and delivers a toxin designed to promote cancer cell death. The drug has been previously approved to treat systemic anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma that has returned after prior therapy.

The FDA’s approval follows the encouraging results of the phase III ECHELON-1 clinical trial, presented at the 2017 American Society of Hematology (ASH) Meeting and Exposition and published in the New England Journal of Medicine. The trial, which was open at Weill Cornell Medicine and NewYork-Presbyterian Hospital, compared standard therapy with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) versus adriamycin, vinblastine and dacarbazine plus brentuximab vedotin (A+AVD).

Of the 1,300+ enrolled patients, those receiving A+AVD were demonstrated to be 23 percent less likely to experience disease progression, a need for additional therapy, or death, as compared to the cohort receiving the standard of care therapy.

Weill Cornell Medicine
Dr. Peter Martin

“ABVD has been the standard therapy for a couple decades because it works really well, but it’s great to have new treatments available for people with Hodgkin lymphoma,” said Peter Martin, Chief of the Lymphoma Program. “I’m proud that we were able to offer this treatment at Weill Cornell a long time ago through the ECHELON-1 trial. Like any treatment, the A+AVD combination may not be right for everyone and requires consideration of side effects, like infection risk and neuropathy. Decisions between patients and physicians regarding the best treatment should follow an open discussion of the evidence.”

 

Dr. John Leonard Comments on the Use of Brentuximab Vedotin as a Monotherapy for Elderly Hodgkin Lymphoma Patients

The Oncology Times reported on results from a small prospective, Phase II open label study published in Blood, that found brentuximab vedotin may be of use for elderly Hodgkin lymphoma patients, who cannot tolerate harsher chemotherapy treatment options. From the 19 patients the objective response rate was 92% with 73% of patients achieving a complete response rate and 19% a partial remission rate. First author, Dr. Andres-Forero-Torres MD reported:

“We took patients who were older than 60 and not candidates for chemotherapy due to comorbidities or who did not want to receive chemotherapy, and we treated them with brentuximab vedotin as a single agent…We were able to show in this small but significant population of patients that older patients tolerated brentuximab vendotin very nicely. We found very high rates of response–almost everybody had a response, and a very good percentage had a complete remission.”

Lymphoma Program Director, Dr. John Leonard commented on the results:

“The issue is that the standard therapies in elderly and frail patients do have significant toxicity, so trying to come up with something that has less toxicity, if it can also be effective, is valuable…Brentuximab vedotin has less toxicity against the lungs, which is an issue with bleomycin, and less in the way of low blood count which you have in standard chemotherapy. It also avoids the cardiac toxicity of standard treatment as well.

Currently there are two trials comparing brentuximab vedotin to other treatment regimens open at Weill Cornell Medicine. The first trial is open to patients with advanced classical Hodgkin lymphoma and the second trial is open to patients with CD-30-positive mature T-cell lymphomas.