Anaheim, CA—Although transplantation offers cures or durable remissions for malignancies, relapse is a frequent occurrence in many diseases, and remains a major cause of mortality.
At the 2017 Hematology/Oncology Pharmacy Association (HOPA) Annual Conference, Sarah Perreault, PharmD, BCPS, BCOP, Clinical Pharmacy Specialist, Bone Marrow Transplantation, Yale New Haven Hospital, CT, highlighted the need for identification of high-risk patients, and for strategies for relapse prevention.
“Prevention is the most feasible and effective means of managing relapse, and is ultimately the best way to protect the patient. There are many strategies for prevention of disease relapse, but maintenance chemotherapy is an essential part of the process,” said Dr Perreault.
As Dr Perreault reported, eligibility for maintenance therapy in multiple myeloma is not well-defined.
“The consensus is that any person with any stage of disease is eligible for maintenance regardless of chromosomal abnormalities. Maintenance is not going to overcome your prognostic score if you have a bad cytogenetic profile, but it does help with progression-free survival, so we recommend that all patients receive some kind of maintenance after transplant with multiple myeloma,” said Dr Perreault.
In randomized controlled trials, low-dose lenalidomide doubled progression-free survival compared with placebo. Although lenalidomide did not affect overall survival, it did give patients longer disease control, said Dr Perreault, who noted that patients are typically started with lenalidomide within the first 90 to 180 days of hematopoietic stem-cell transplantation, and that duration of therapy can extend beyond 2 years.
Where cost is an issue, bortezomib may be an option for maintenance therapy, offering approximately the same progression-free survival as lenalidomide, and fewer adverse events and second primary malignancies, she said.
In the future, pomalidomide may provide an additional option in the maintenance setting, and ixazomib, an oral proteasome inhibitor described as a “potential game-changer,” is coming down the pipeline, as well.
Relapsed or primary refractory Hodgkin’s lymphoma can be cured in 50% of patients after autologous hematopoietic stem-cell transplantation, Dr Perreault reported, but there are risk factors associated with poor prognosis, including primary refractory disease, an initial remission duration of <1 year, or the presence of extranodal or advanced-stage disease at the time of relapse. According to National Comprehensive Cancer Network guidelines, lack of chemosensitivity to pretransplant salvage or residual disease at the time of transplant are also associated with poor prognosis.
Brentuximab is currently used for maintenance therapy, based on the results of a randomized clinical trial that demonstrated significant improvement in progression-free survival compared with placebo (61% vs 43%, respectively, at 3 years).
“You’re not going to see it with these data, but there probably is an overall survival benefit, as well,” said Dr Perreault, who noted that an increased number of risk factors was associated with greater benefit in terms of progression-free and overall survival.
The optimal duration of brentuximab therapy is 1 year, but discontinuation because of adverse effects is common. Peripheral neuropathy occurred in 88% of patients.
Patients with acute myeloid leukemia who harbor an FLT3 mutation have high relapse rates, and may require the use of maintenance therapy. Sorafenib, a tyrosine kinase inhibitor, has shown benefits, said Dr Perreault, but only phase 1 data are currently available.
For patients with Philadelphia chromosome–positive leukemia, imatinib, another tyrosine kinase inhibitor, has been shown to improve overall survival in patients with chronic myeloid leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia. The presence of minimal residual disease after transplant is predictive of relapse, Dr Perreault reported.