The American Society of Clinical Oncology (ASCO) is the world’s leading organization for physicians and oncology professionals caring for people with cancer. The 2021 Annual Meeting was hosted virtually, connecting oncology professionals from around the world to discuss the newest, state-of-the-art research and treatment updates.
The Weill Cornell Lymphoma Program team is always proud of our contributions to new lymphoma research presentations at the ASCO Annual Meeting. We’ve outlined some of the highlights from this year’s conference, including research updates and new discoveries from our team. Additionally, our Weill Cornell Medicine and NewYork-Presbyterian Hematology & Oncology Fellow Dr. Sam Yamshon received a prestigious ASCO Conquer Cancer Foundation 2021 Young Investigator Award to support critical lymphoma research and the transition from fellowship to faculty.
Weill Cornell Lymphoma Program Chief Dr. Peter Martin presented new mantle cell lymphoma research and shared important insights about care in the community or real-world setting as part of an oral abstract session.
PET scan imaging during treatment for bulky Hodgkin lymphoma can provide critical information to shape the course of care. Dr. John Leonard breaks down this NCI-supported ALLIANCE research presented this year’s ASCO meeting.
The multi-center phase 2 study, led by study chair Dr. Jia Ruan, was initiated in 2011 and previously reported early efficacy in the New England Journal of Medicine (NEJM) and 5-year follow-up results in Blood, which was highly effective with an overall response rate (ORR) of 92%, and complete response (CR) of 64%. It was also well tolerated, with durable responses, including the 5-year progression free survival (PFS) and overall survival (OS) of 64% and 77% respectively. Dr. Samuel Yamshon, a second-year hematology and medical oncology fellow at Weill Cornell Medicine and NewYork-Presbyterian Hospital led the oral presentation of the 7-year follow up analysis at this year’s ASH meeting.
The study treatment is conveniently administered in the outpatient setting, with the oral agent lenalidomide given on days 1-21 of a 28-day cycle and rituximab provided once very other cycle during maintenance. The treatment continues until progression of disease, with an option to stop therapy after 3 years of remission.
A total of 38 clinical trial participants were enrolled at four participating centers across the United States. Of the 36 evaluable patients, 19 (53%) of the patients remain in remission, including 12 (33%) beyond 7 years. Of the patients in remission, 10 remain on treatment, while 9 patients in remission opted to stop therapy after at least 3 years of study treatment due to side effects or patient preference. The median progression free survival (PFS) and duration of response have not been reached. The 7-year PFS rate was estimated at 60%, and 7-year OS rates at 73%. With long-term maintenance treatment, there were no new safety concerns, and close follow up limited toxicity for those who wished to remain on therapy.
The long-term outcome of the lenalidomide plus rituximab regimen represents a major stride in the treatment and care of MCL patients – a population of patients who harbor a rare and generally incurable disease where intensive chemotherapy regimens do not necessarily translate into cure and may not be tolerated by all. It is notable that this combination therapy offers a chemotherapy-free initial treatment approach that compares favorably in outcome to conventional chemotherapy-based regimens such as bendamustine-rituximab, VR-CAP, and R-CHOP with rituximab maintenance. The National Comprehensive Cancer Network (NCCN) has incorporated this evidence into their treatment guidelines for MCL patients. The Weill Cornell Lymphoma Program researchers concluded that the evaluation of this active regimen in larger, randomized frontline trials comparing novel agents with chemoimmunotherapy is warranted.
Today, at the 2020 Annual Meeting of the American Hematology Society (ASH), the Weill Cornell Medicine T-cell lymphoma research team reported the outcome of the first phase 2 study evaluating the novel combination of oral azacitidine plus CHOP as initial treatment for patients with peripheral T-cell lymphoma (PTCL).
This multi-center phase 2 study, led by Dr. Jia Ruan, is the first of its kind to incorporate epigenetic priming with a hypomethylating agent in the frontline setting as a chemo-sensitizing strategy for PTCL.
The study enrolled 21 PTCL patients, with the majority of them (17 patients) having the diagnosis of angioimmunoblastic T-cell lymphoma, also known as PTCL with T-follicular helper phenotype (PTCL-TFH). This phenotype is known to have recurrent genetic mutations in epigenetic regulation, providing therapeutic targets for hypomethylating agents such as azacitidine. During study treatment, the patients received CHOP on day 1 of each cycle for 6 cycles, while oral azacitidine was given for 7 days prior to CHOP cycle 1, and for 14 days before CHOP cycles 2-6. The primary study objective was to see if the novel combination would improve complete response rates following 6 cycles of treatment.
The study treatment was well tolerated with expected side effects associated with CHOP chemotherapy. Eighteen patients were able to complete all 6 cycles of treatment without the need for chemotherapy dose reduction. Ten patients underwent successful stem cell transplant while in remission. Complete remission (CR) was achieved in 75% of clinical trial participants at the end of 6 cycles of treatment, exceeding the pre-determined efficacy threshold (60%) to declare the treatment as effective. Notably, within the subgroup of patients with the PTCL-TFH subtype, the treatment appears to work even better with a CR rate of 88%. The one-year progression-free survival (PFS) for all patients was 66%, and for the PTCL-TFH subgroup was 70%. The one-year overall survival (OS) for all patients was 81% and PTCL-TFH patients 94%. The research team is further analyzing sequencing biomarkers to correlate with response and survival.
This study provides the first demonstration that the addition of epigenetic hypomethylating agent oral azacitidine (CC486) to CHOP as initial therapy is safe, and highly effective to induce complete remission in PTCL. This combination will be further evaluated in the upcoming ALLIANCE/Intergroup randomized study A051902, comparing oral azacitidine-CHO(E)P with duvelisib-CHO(E)P against CHO(E)P in CD30 negative PTCL.