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.
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma, rising in incidence among older populations. The standard of care for the approximate one-third of DLBCL patients who do not achieve remission with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) is salvage high-dose chemotherapy followed by consolidative autologous stem cell transplant, which leads to long-term disease-free survival for only 10-20 percent of relapsed/refractory patients. Patients who relapse within a year of initial therapy, those who relapse after transplant, and those who are ineligible for transplant due to age or comorbidities face the most significant unmet treatment need.
With an eye toward improving therapeutic options and outcomes for this patient population, the Lymphoma Program team, led by Dr. Jia Ruan, collaborated with colleagues nationwide and contributed significantly to a study examining the maximum tolerated dose and preliminary safety and activity of a novel three-drug combination – ibrutinib plus lenalidomide and rituximab – in treatment of relapsed/refractory DLBCL. The team’s encouraging findings were published in the American Society of Hematology’s Blood journal.
The study population consisted of 45 transplant-ineligible DLBCL patients whose disease returned after at least one prior therapy. Patients received oral ibrutinib daily, intravenous rituximab on every first day of six 28-day cycles, and oral lenalidomide on the first 21 days of each cycle. The treatment was provided as continuous chronic therapy in an outpatient clinic setting for as long as patients could derive benefit.
Forty-four percent of patients responded to the triplet, and 28 percent achieved a complete response. The combination performed particularly well (ORR: 65%, CR: 41%) in patients with non-germinal center b cell (non-GCB) DLBCL, a molecular subtype based on disease cell of origin that is not typically associated with favorable prognosis. Common treatment side effects included gastrointestinal complications, fatigue, myelosuppression (reduced blood cell production), hypokalemia (low blood potassium), peripheral edema and skin rash. Side effects could be monitored and mitigated by dose adjustment in the outpatient setting.
“This novel treatment consists of two oral agents typically used to treat B-cell lymphoma, plus the anti-CD20 antibody rituximab, and can be easily administered in the clinic or patient’s home,” said Dr. Jia Ruan. “This effective low-intensity approach makes it very appealing to a broad range of R/R DLBCL patients in need of treatment.”
The oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has become a mainstay in the treatment of mantle cell lymphoma (MCL), producing a response in nearly 70 percent of all patients. Yet, the majority of MCL patients treated with ibrutinib develop resistance to the drug within about a year.
Preclinical research conducted at Weill Cornell Medicine demonstrated that sustained inhibition of CDK4 (a protein that promotes growth of MCL cells) by the oral drug palbociclib can not only prevent proliferation of MCL cells, but also make them more sensitive to attack by ibrutinib.
Based on these findings, Weill Cornell Medicine and NewYork-Presbyterian Lymphoma Program Chief Dr. Peter Martin and colleagues initiated a phase I study of palbociclib plus ibrutinib (PALIBR) in patients with previously treated MCL. Results from the all-oral regimen were recently published online in the American Society of Hematology (ASH) Blood Journal.
The addition of palbociclib to ibrutinib appeared to produce deeper, more durable responses compared to what is traditionally produced by ibrutinib alone, with over half of all patients remaining free of disease progression at the two-year post-treatment mark. The most prevalent side effect was low blood counts.
“The first person to be treated on the study in August of 2014 achieved a complete response within three months and remains in a complete response today,” said Dr. Martin. “We were all excited by the results.”
Physicians and researchers at the Lymphoma Program look forward to learning more about the efficacy of PALIBR in the ongoing AFT-32 phase II trial, which incorporates genetic profiling that may help to identify the features associated with drug resistance.