By Peter Martin, M.D.
Data from three pooled clinical trials suggest that, by itself, ibrutinib works to keep mantle cell lymphoma (MCL) at bay for about one year. For reasons that we have previously discussed on this blog, these results are both impressive and discouraging. For people with MCL, ibrutinib is singular in its ability to produce durable remissions with minimal toxicity. Unfortunately, roughly one third of patients do not respond, while all responding patients eventually experience relapse or progression.
Data from the Chen-Kiang laboratory at Weill Cornell Medicine suggested that palbociclib, an oral inhibitor of CDK4/6, could prevent MCL cells from growing and dividing. Moreover, these arrested MCL cells become even more sensitive to the effects of ibrutinib, essentially overcoming some of the more common mechanisms of ibrutinib resistance and laying the groundwork for a clinical trial.
With the support of the National Cancer Institute, doctors at Weill Cornell Medicine, Ohio State University, Washington University, and the University of North Carolina initiated a phase I clinical trial designed to evaluate the safety and activity of ibrutinib plus palbociclib in people with previously treated MCL. I presented the results of the trial at the 2016 Annual Meeting of the American Society of Hematology. The early results of the trial appear promising, with 70% of patients responding including 45% of study patients experiencing a complete response. More interesting is the observation that only one responding patient has experienced lymphoma progression, corroborating the Chen-Kiang laboratory data that the combination might overcome some mechanisms of ibrutinib resistance. So far, the all-oral regimen appears well tolerated, with low blood counts being the primary side effect.
Although these data appear promising, the number of patients treated so far is relatively small and the follow up time is relatively short. A large, multicenter phase II trial is being planned and will likely open in early 2017. Details regarding that study will be available on this blog and clinicaltrials.gov as soon as they become available.
Palbociclib is a selective CDK4/6 inhibitor approved by the FDA for the treatment of patients with breast cancer. Currently it’s being tested in phase I trials for the treatment of patients with mantle cell lymphoma. The use of palbociclib as a cancer treatment was championed by Selina Chen-Kiang, PhD., professor of Pathology & Laboratory Medicine and Microbiology & Immunology, and a key collaborator with the Lymphoma Program. Palbociclib is currently considered one of the next big things in cancer treatment. But:
“..it’s old news for Selina Chen-Kiang, Ph.D…who has been a cheerleader for palbociclib for the past decade. In fact, her relentless effort helped resurrect the drug after it was shelved by an uninterested pharmaceutical company, and her initial findings inspired the clinical trials that paved the path for its accelerated approval.”
“Chen-Kiang is renowned for her research in immunology and hematological malignancies. A molecular biologist by training, she first got swept into myeloma and lymphoma research while studying how antibody-secreting plasma cells were generated from B cells. Unlike solid tissue, normal immune cells can be isolated at different stages from mice and humans, making them the perfect model to study her primary passion: cell cycle control of immunity.”
Today Dr. Chen-Kiang’s dogged inquiry into the potential of palbociclib has the potential to help cancer patients. Her resolve exemplifies the bench portion of our bench to bedside approach at the Meyer Cancer Center. Palbociclib is currently undergoing phase I investigator-initiated trials, sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute at Weill Cornell Medical College. The principle investigator is Dr. Peter Martin. You can listen to him explain explain the benefits of this recently initiated trial:
In this video Dr. Peter Martin explains the benefits of a recently opened phase I trial of ibrutinib plus palbociclib for patients with previously treated mantle cell lymphoma (MCL). The trial will evaluate the safety and activity of the combination. This is a Weill Cornell Medical College investigator-initiated clinical trial, sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute.
If you’re interested in participating in this trial please call 646-962-2074 for more information.