Mantle Cell Lymphoma PALIBR Outcomes Published Online in Blood Journal

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.

Weill Cornell Medicine“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.

Promising Long-Term Outcome of Chemo-Free Mantle Cell Lymphoma Treatment Published in Blood Journal

The long-term outcome of the first-ever study of a non-chemotherapy frontline treatment approach to mantle cell lymphoma (MCL) was recently published in the American Society of Hematology’s prestigious Blood Journal.

Led by Dr. Jia Ruan, clinical investigators at four medical centers across the United States launched a phase two clinical trial in 2011 to evaluate the novel biological pairing of lenalidomide plus rituximab as induction (initial) and maintenance (relapse prevention) therapy. The team’s treatment goals were to provide disease control and extend survival, while maintaining quality of life.

Read more about the study here.

Of 36 evaluable patients, about 92 percent responded to treatment, with 64 percent achieving complete remission. At five-year follow-up, 77 percent of participants were alive and well, and 64 percent remained free of disease progression.

To determine how well the lenalidomide plus rituximab combination works, the team also measured the status of minimal residual disease (MRD) – the small amount of cancer cells that may be left after treatment that have the potential to lead to relapse. Eight out of a subset of ten evaluable patients tested MRD-negative.

Overall, the chemotherapy-free drug combination has produced durable remission rates with potential to achieve MRD-negative remissions. Chronic maintenance therapy with lenalidomide and rituximab has manageable side effects, including infections, cytopenias (low blood count), and some expected secondary primary malignancies.

This outcome represents a major stride in treatment and care of the MCL patient population, who harbor a rare and generally incurable disease where intensive chemotherapy regimens do not necessarily translate to cure and may not be tolerated by all patients.

Ruan Face“The introduction of novel agents – including the immunomodulatory agent lenalidomide and Bruton’s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib, which are FDA-approved for MCL – is poised to transform MCL management by making effective ‘chemo-free’ treatment accessible to all patients in both relapsed/refractory and frontline settings,” says Jia Ruan, MD, PhD.

 

Lymphoma Program Hosts Oncologists from Brazil for Hematologic Malignancies Update

A group of more than 20 Brazilian oncologists traveled to Weill Cornell Medicine and NewYork-Presbyterian Hospital from South America to attend the 2017 Update in Hematologic Malignancies, a two-day interactive educational symposium organized and presented by members of the Weill Cornell Lymphoma Program’s research and clinical faculty. BrazilianHeme

The meeting, directed by Dr. Sarah Rutherford, featured didactic lectures on chronic lymphocytic leukemia (CLL) and Richter’s Transformation (RT) by Drs. John Allan and Richard Furman, discussions of controversies and challenging cases in mantle cell, follicular and diffuse large B-cell lymphomas (MCL, FL, DLBCL) led by Drs. Rutherford and Peter Martin, a lymphoma-specific hematopathology update from Dr. Amy Chadburn, and a tour of Dr. Leandro Cerchietti’s research laboratory.

Programs like this one foster partnerships that can propel us toward our goal of improving health outcomes for the nearly 100,000 people around the world who are affected by lymphoma. Our team is able to establish collaborative international relationships to teach and learn from medical practitioners of a diverse background, all while solidifying our role as a trusted, global authority on lymphoma research and care.

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Dr. Sarah Rutherford

“The relationship we have established with the Brazilian oncologists is fulfilling for all of us,” says Dr. Rutherford. “We enjoy teaching them and helping to manage complex cases that they face in Brazil. We also remain in touch with them after the conference – providing guidance on patients and even traveling to Brazil to participate in meetings. We look forward to continuing this collaboration given our shared mission of providing the best possible care for patients with lymphoma.”