Authored by Brian Koffman, MDCM (retired), MSEd
Bottom Line
A large prospective collaborative trial tests whether adding pirtobrutinib to standard R-CHOP improves outcomes in Richter transformation.
Background:
Richter transformation is a rare complication when chronic lymphocytic leukemia / small lymphocytic lymphoma or CLL / SLL transforms from a slow growing leukemia / lymphoma into an aggressive related large B cell lymphoma or LBCL that responds poorly to most therapies and carries a dismal prognosis often measured in mere months of overall survival.
The backbone of treatment has been traditional chemo-immunotherapy cocktails, most commonly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) which works well with most of the common variants of LBCL but definitely not for those with RT. Recently, some research has suggested that adding pirtobrutinib, a noncovalently binding BTK inhibitor (nBTKi), to other therapies might improve RT outcomes.
Who is doing the Research and What is the Method:
As RT is a relatively rare cancer, this is the first large-scale prospective randomized control collaborative study of the combination of R-CHOP with or without pirtobrutinib. It is sponsored by the National Cancer Institute (NCI) and run by SWOG (SouthWest Oncology Group). There will be multiple trial sites across the USA when the trial is fully open. Patient must have previously untreated RT. Outcomes include comparing Progression Free Survival (PFS) and Overall Survival (OS) between the arms with and without pirtobrutinib. CLL Society’s Dr. Koffman volunteers as one of two patient advocate members on the NCI Leukemia Steering Committee that determines which studies like this one get NCI government funding.
Dr. Mazyar Shadman of the Fred Hutch in Seattle, WA, is the principal investigator.
Conclusions:
RT remains one of the most pressing unsolved challenges in the CLL / SLL community. Results with CIT and with novel therapies alone have been disappointing, and unlike the rapid improvements we’ve seen in outcomes in CLL / SLL itself, progress in RT has been slow with no dramatic advances. This large, randomized controlled trial that combines the standard of care CIT of R-CHOP with the encouraging results seen with pirtobrutinib alone or in other combinations in smaller data sets is an important step forward in moving the needle in a positive direction. Arguably, more so in RT than in any other CLL circumstance, a clinical trial such as this one may be a patient’s best option.
Resources:
To learn more about the trial and how you might find out whether it’s appropriate for you or a loved one, please visit: Adding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial at Clinicaltrials.gov.
Please enjoy my interview with Dr. Shadman
