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Vikas Gupta, MD, FRCP, FRCPPath
Princess Margaret Cancer Centre University Health Network, Toronto, Canada
How can we best study transplant vs best available non-transplant therapies in myelofibrosis patients?
According to Dr. Vikas Gupta, studies have shown that high-risk myelofibrosis (MF) patients appear to have better survival with hematopoietic stem cell transplants (HCT) than with best available non-transplant therapies (BAT). But how do we study this prospectively – the efficacy of HCT versus BAT in MF – with the challenges of both a rare disease and a patient population with strong preferences about one or the other?
These obstacles make a randomized study logistically difficult. So, Dr. Gupta and colleagues set out to create and test a new study design, with the support of MPN Research Foundation through a 2021 MPN Challenge™ award titled: Allogenic Hematopoietic Cell Transplantation Versus Best Available Non-Transplant Therapies in Patients with Myelofibrosis (ALLO-BAT Study).
The project was designed to test the feasibility of a patient-preferences controlled multi-center prospective study to compare the efficacy of HCT vs. BAT in high-risk MF using molecular integrated risk scores,” says Dr. Gupta. It will be done by asking participants to choose the treatment that they prefer to receive (HCT or BAT) and then comparing the outcomes of the participants in both treatment groups.
“With this trial, we are addressing an important clinical dilemma – what is the optimal timing of the transplant in myelofibrosis,” he explains. “This issue has not been addressed in the past prospectively. We are hoping the findings of this study provide some evidence whether the current study design is feasible to answer this question.”
Confirming feasibility of the study design that incorporates patient therapy preferences will facilitate a future expanded study of HCT vs. BAT, according to Dr. Gupta. The original goal of the study was to recruit 72 patients. COVID-19 restrictions dramatically impacted the expected progress, which now has a target date for completion of April 2025.
To help speed up progress, the study was expanded to six additional clinical trial sites throughout Canada and potentially in Australia/New Zealand, as well as through the multi-institutional MPN Research Consortium.
While there are no specific outcomes to present yet, the research team is hopeful that within the next 12 months they will be able to compare the survival and longitudinal quality of life of patients undergoing hematopoietic cell transplant as compared to those who chose best available non-transplant treatment. They also hope to determine whether this feasibility study is possible to move forward to full clinical trials.
The year Dr. Gupta became interested in the field of MPNs, 2004, was the same year the JAK2 mutation was described. “At that time there was no programmatic approach to treat or study these disorders in Canada,” he says. “These diseases were ignored by the cancer agencies in Canada due to poor understanding … lack of funding and the rarity of the disease were major barriers to develop an academic career in this area.” As a result, there was not a lot of interest among physicians/scientists.
As his story continues, it exemplifies the roots of organic growth that feeds today’s evolution of MPN research and practice.
After overcoming a number of challenges, Gupta et al were able to be a part of the independent MPN Research Consortium, which allowed them to bring clinical trials to Princess Margaret for the past 15 years. This availability of clinical trials led to exponential growth in the number of referrals to the cancer centre.
“To deal with increasing volume of referrals in a limited space, we created a shared care (outreach) model for care of patients with MPN. We were able to provide access to MPN expertise to a large number of patients in community – where the majority of care was provided near to home. Aspects of care which cannot be provided near home, such as complex decision making, access to clinical trials, diagnostic issues, etc. were provided at Princess Margaret.”
Ten clinical research fellows have been trained to date within the MPN program established at Princess Margaret in 2014. Many now lead their own independent programs, having become faculty in various centers in Canada and other countries, including Australia, India, and Saudi Arabia.
Dr. Gupta goes on to mention several influential mentors in his career: Dr. Armand Keating at Princess Margaret; Dr. Judith Marsh at King’s College Hospital, London; and Dr. Ronald Hoffman, Mount Sinai, New York, and a long-time valued advisor to MPN Research Foundation. “They helped in developing my critical thinking and supported my career with valuable advice.”
MPN Research Foundation previously funded other studies looking at transplant outcomes in MF, including an abstract from 2023 ASH (American Society of Hematology) which was published in the journal Blood. In that study, Roni Tamari, MD, et al, Memorial Sloan Kettering, conducted a large multi-center retrospective analysis of molecular impacts on HCT. They examined the results of 498 patients from 11 centers in North America and Canada to assess the association of patient, transplant, and disease characteristics on overall survival (OS). The results suggested that, with respect to overall survival, transplant can overcome somatic (acquired) mutations associated with MF, and that blood counts and other clinical biological factors were a more prognostic indicator of OS than the presence of so called “high risk” mutations.